Efficacy and Safety of Pericapsular Nerve Group Block for Hip Fracture Surgery under Spinal Anesthesia: A Meta-Analysis

Objective To evaluate the effectiveness and safety of pericapsular nerve group (PENG) block for hip fracture surgery under spinal anesthesia. Methods This meta-analysis was registered on INPLASY (INPLASY202270005). PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched to collect the randomized controlled trials of the PENG block applied to hip fracture surgery in the setting of spinal anesthesia, with the search period from inception to 1 May 2023. Two independent researchers gradually screened the literature, evaluated the quality, extracted the data, and eventually pooled data using RevMan 5.4. Results Fifteen articles with 890 patients were enrolled. The combined results showed that the PENG block reduced pain scores during position placement (SMD = −0.35; 95% CI [−0.67, 0.02]; P=0.04; I2 = 0%). Subgroup analyses showed that compared to the unblocked group, the PENG block reduced pain scores at 12 h, 24 h, and 48 h postoperatively. The incidence of postoperative hypokinesia was reduced (RR = 0.11; 95% CI [0.01, 0.86]; P=0.04; I2 = 0.00%). The time to first walking was advanced (SMD = −0.90; 95% CI [−1.17, 0.63]; P < 0.00001; I2 = 0%). Conclusion The PENG block can reduce postoperative pain and pain during spinal anesthesia positioning, which is helpful to improve the operability and comfort of spinal anesthesia and facilitate postoperative muscle strength recovery and early activity.


Introduction
Hip fracture is one of the standard clinical fractures, and its incidence has increased signifcantly, especially among people over 65 years old.Hip fracture is a severe trauma due to osteoporosis and trauma, etc.It is accompanied by severe pain, complications can be disabling or even life-threatening, and surgical treatment is used as its primary treatment [1].Spinal anesthesia is still one of the most commonly used methods [2].However, severe pain caused by fractures often leads to difculties in placement and positioning of the spinal anesthesia position, making spinal anesthesia more challenging to perform, and poor management of postoperative pain and other complications can signifcantly impact the patient's early recovery [3].Terefore, fnding an efective solution to synergize spinal anesthesia is essential.
Recently, the pericapsular nerve group (PENG) block of the hip joint has gained increasing attention, frst described by Giron-Arango et al.Te PENG block, usually performed under ultrasound guidance, is performed by injecting local anesthetic drugs to block the articular branches of the femoral nerve (FN), the obturator nerve (ON), and the accessory obturator nerves (AON), among others.Tese nerves provide sensory innervation to the anterior hip capsule [4] to achieve its analgesic efect.Te PENG block has been reported to have the advantages of easy operation, fewer complications, better postoperative analgesia, and the ability to be performed in the supine position, and it can reduce pain without afecting motor function [5].Terefore, patients undergoing the PENG block can get out of bed as early as possible, reducing the incidence of postoperative complications and facilitating early recovery [6].
Although some clinical studies have reported the application of the PENG block in hip fracture surgery, there is no conclusion about its efectiveness and safety for hip fracture surgery under the circumstances of spinal anesthesia.In this study, we conducted a meta-analysis of published high-quality RCTs to systematically evaluate the efectiveness and safety of the PENG block for hip fracture surgery under spinal anesthesia and to provide evidence-based medical evidence and reference basis for clinical practice.

Methods
2.1.Search Methods.Tis meta-analysis was registered on INPLASY (INPLASY202270005).Our meta-analyses were performed according to PRISMA reporting standards.Te search strategy was a comprehensive search of PubMed, Cochrane, Embase, CNKI, and Wanfang databases.Te essential English search terms were "PENG block," "Pericapsular Nerve Group block," "Femoral Neck Fracture," and "hip fracture."Randomized controlled trials on the PENG block were collected.Te search date was from the establishment of the database to 1 May 2023, and the search languages were English and Chinese, using a combination of subject terms and free words and adjusted according to the characteristics of each database.Te references of the included studies were also searched to obtain additional relevant information.Detailed methodology can be referred to previous words [7][8][9][10].Te detailed search strategy is shown in Figure 1.

Study Selection and Data Collection.
Te initial retrieved literature was imported into Endnote 20, duplicates were excluded, and two researchers independently screened the literature, extracted the information, and cross-checked it; in case of disagreement, a third researcher was consulted to assist in the adjudication, and the lack of information was replenished by contacting the authors as much as possible.Te data extracted included authors, year of publication, time of nerve block operation, number of people in intervention and control groups, postoperative remedial analgesic medications, and adverse efects.Pain scores (including numerical analog scales NRS and VAS) at each postoperative time point, which were converted to VAS (1-10 cm) for diferent pain scales [11,12]; opioid consumption at 24 and 48 hours postoperatively, which needed to be converted to an equivalent amount of morphine if it was not morphine [13]; time of the frst postoperative remedial analgesia; time of the operation of the spinal anesthesia; the time of the frst postoperative ambulation out of bed; and the incidence of postoperative nausea and vomiting.Details are provided in Table 1.

Risk of Bias Assessment.
Two independent researchers evaluated the included literature using the Cochrane Risk of Bias Assessment System.Evaluation entries included random sequence generation, allocation concealment, blindness of participants, outcome evaluators, completeness of outcome data, selective reporting of outcome indicators, and other biases.ReviewMan 5.4 was applied to map the risk of bias assessment, see Figure 2.

Statistical Analysis.
Data were processed using RevMan 5.4.Continuous variables were described by the standardized mean diference (SMD) and 95% confdence interval (CI) and dichotomous variables by the relative risk ratio (RR).Heterogeneity between studies was evaluated using I 2 values; with I 2 ≤ 50%, no heterogeneity was considered to exist, and a fxed-efects model was selected; with I 2 > 50%, signifcant heterogeneity was considered to exist, and a random-efects model was selected.Subgroup analyses (subgroup analyses were performed using diferent modes of basal analgesia in the control group) were used to fnd sources of heterogeneity.
2.5.Assessment of Evidence Quality.Te GRADE profler software was used to evaluate the quality of the evidence for the results of the combined analysis, and a high-, medium-, low-, or very low-quality evidence rating was made for each outcome, which was used to evaluate the quality of the evidence and the strength of the recommendations, as shown in Table 2.

Characteristics of Included
Studies.Among all the included literature, there were ffteen articles in the intervention group in which the PENG block was performed, including eleven articles in which the PENG block was performed before spinal anesthesia and four articles in which the PENG block was performed after spinal anesthesia; a total of ffteen articles were included in the control group, in which no PENG block was performed, including seven articles in which the fascia iliaca compartment block (FICB) was performed (fve in which FICB was performed before spinal anesthesia and two in which FICB was performed after spinal anesthesia) and eight in which no neural block was performed.Outcome metrics were reported in eight papers that reported time to frst postoperative remedial analgesia, three papers that reported time to frst postoperative ambulation, two papers that reported time to spinal anesthesia manipulation, a total of six papers that reported on the occurrence of postoperative hypokinesia, and eight papers that reported on the incidence of PONV.Four literature results were reported as the median and interquartile range (IQ range), which were converted according to the appropriate formulas.Tere was one literature with results reported in a graphical form.Te essential characteristics of the included studies are tabulated in Table 1.

Methodological Quality Assessment.
According to the Cochrane Risk of Bias Assessment System, among the literature we included, there were eight high-quality papers 2 International Journal of Clinical Practice [5,15,17,[19][20][21][22]25], three low-quality papers [2,14,24], and four papers with unclear literature quality [16,18,23,26].Te results are shown in Figure 2.  3).Pain scores were reduced in the PENG block group compared with the control group, and the diference was statistically signifcant (P < 0.05).After sensitivity analysis, excluding any of the studies did not change the direction of the results, indicating stable results.According to the subgroup analysis through the control group of diferent essential analgesia before spinal anesthesia (FICB subgroup before spinal anesthesia, no nerve block subgroup), the results are shown in Table 3.Compared with the FICB group before spinal anesthesia, the diference in pain scores between the PENG block group was not statistically signifcant; compared with the no nerve block group before spinal anesthesia, the pain scores of the PENG block group were reduced, and the diference was statistically signifcant (P < 0.05).

Efects of Interventions
(2) Postoperative Pain Scores (VAS).We extracted postoperative pain scores at 6 h, 12 h, 24 h, and 48 h.A total of 3-5 papers were included in this outcome metric, which was as follows: at 6 h postoperatively (SMD � −0.08; 95% CI [−0.33, 0.17]; P � 0.53; I 2 � 0%, Figure 3); at 12 h postoperatively (SMD � −0.70; 95% CI [−1.43, 0.03]; P � 0.06; I 2 � 88%, Figure 3); at 24 h postoperatively (SMD � −0.25; 95% CI [−1.29, 0.80]; P � 0.64; I 2 � 93%, Figure 3); and at 48 h postoperatively (SMD � −0.35; 95% CI [−0.67, −0.02]; P � 0.04; I 2 � 0%, Figure 3).Compared with the control group, the pain score was reduced in the PENG block group at 48 h postoperatively, and the diference was statistically signifcant (P < 0.05); the diference was not statistically signifcant at 6 h, 12 h, and 24 h postoperatively.Te above was analyzed by sensitivity analysis, and excluding any of the studies did not change the direction of the results, indicating that the results were stable.According to the subgroup analysis through the control group of diferent primary analgesic modalities (FICB subgroup, not nerve block subgroup), the results are shown in Table 3.Compared with the FICB subgroup, the PENG block group postoperative International Journal of Clinical Practice (3) Te Incidence of Postoperative Hypokinesia.Te incidence of postoperative hypokinesia was defned as postoperative knee or hip dyskinesia.A total of fve papers were included for this outcome index, and the results were as follows: (RR � 0.11; 95% CI [0.01, 0.86]; P � 0.04; I 2 � 0.00%, Figure 4).Te incidence of postoperative hypokinesia was reduced in the PENG block group compared with the control group, and the diference was statistically signifcant (P < 0.05).Subgroup analysis was performed according to the diferent primary analgesia modalities in the control group (FICB subgroup, no nerve block subgroup), and the results are shown in Table 4. Compared with the FICB subgroup, the PENG block reduced the incidence of postoperative hypokinesia, with a statistically signifcant diference (P < 0.05); compared with the no nerve block group subgroup, there was no statistically signifcant difference between the diferences in the incidence of postoperative hypokinesia in the PENG block group.(3) Te Time to First Postoperative Remedial Analgesia.Te time to frst postoperative remedial analgesia, defned as the time from the end of the operation to the patient's frst request for analgesic medication, was included in this result in eight papers.Te time to frst postoperative remedial analgesia (SMD � 1.38; 95% CI [0.41, 2.34]; P � 0.005; I 2 � 95%) was delayed in the PENG block group when compared to the control group, with a diference of statistical signifcance (P < 0.05).After sensitivity analysis, the exclusion of any of the studies did not change the direction of the results, indicating stable results.Subgroup analyses were performed by diferent primary analgesic modalities in the control group (FICB subgroup, unnerve block subgroup), and the results are shown in Table 6.Compared with the FICB subgroup, the PENG block group could not delay the time of the frst postoperative remedial analgesia.Te difference was not statistically signifcant, and compared with the unnerve block group subgroup, the PENG block group could delay the time of the frst postoperative remedial analgesia.Te diference was statistically signifcant (P < 0.05).

Secondary Outcome
(4) Te Time of the spinal anesthesia operation.Te time of the spinal anesthesia operation was included in 2 papers, and the control group was without a nerve block.Te results were as follows: (SMD � −1.29; 95% CI [−2.54, −0.03]; P � 0.04; I 2 � 84%), and the spinal anesthesia operation time was shortened in the PENG block group compared with the control group, with a statistically signifcant diference (P < 0.05).After sensitivity analysis, excluding any of the studies did not change the direction of the results, indicating that the results were stable.
(5) Te Time to First Walking.Te time to frst walking, defned as the time to frst get out of bed after the end of the operation, was included in a total of three papers.Te results were as follows: (SMD � −0.90; 95% CI [−1.17, −0.63]; P < 0.00001; I 2 � 0%, Figure 5), the time to frst walking was advanced in the PENG block group compared with the control group, and the diference was statistically signifcant (P < 0.05).
(6) Te Incidence of Postoperative PONV.A total of eight papers were included, and the results were as follows: (RR = 0.67; 95% CI [0.34, 1.32]; P � 0.25; I 2 = 0.00%), there was no diference of the incidence of postoperative nausea and vomiting between PENG blockade and control group, the diference was not statistically signifcant.Te quality of evidence for each indicator was evaluated using the GRADE profler software.Te results showed that there was no highintensity evidence.Moderate-intensity evidence supports that the PENG block reduces postoperative 48 h pain, decreases the incidence of postoperative muscle strength reduction, and advances the time to frst ambulation but does not reduce postoperative 6 h pain or the incidence of PONV.Low-equal-strength evidence supports that the PENG blockade does not reduce 48 h postoperative opioid consumption.Very low equal-intensity evidence supports that the PENG blockade reduces pain at the time of spinal anesthesia placement position at 12 h and 24 h postoperatively, reduces opioid consumption at 24 h postoperatively, delays the time to frst remedial analgesia, and reduces the time to spinal anesthesia manipulation.Te overall quality of the evidence was low, and there is a need to look for higherquality evidence to demonstrate these points in upcoming studies.

Summary of Main Results.
A total of ffteen studies were included in this meta-analysis to analyze the efects of the PENG block in spinal anesthesia for hip fracture surgery on spinal anesthesia operation, postoperative analgesic efect, postoperative muscle strength recovery, and early activity with postoperative nausea and vomiting.Musculoskeletal disease remains the disturbing issues for people worldwide [27][28][29][30].It has been found that the PENG block can reduce patients' pain during spinal positioning, and the PENG block can reduce the efect on the quadriceps muscle strength so that the patients can get out of bed early.Although heterogeneity was high, sensitivity analyses showed that the results were stable and would not be altered by excluding a particular study.Te sensory-motor dissociative efect of the PENG block was signifcantly better than that of FICB.Te efectiveness of the PENG block for analgesia was demonstrated from the results of postoperative pain scores and patients' postoperative opioid consumption, which reduced opioid application due to the inhibition of nociceptive sensitization by better suppression of pain signal conduction from the periphery to the spinal cord at an early stage, based on whether or not the nerve block was used in the control group, and the results of our subgroup analyses showed that the PENG block group was comparable to FICB in reducing patients' postoperative pain.Te lack of efect of the PENG block on the incidence of PONV may be due to the importance of PONV prevention and treatment through multimodal programs.It cannot be determined solely by the PENG block alone.

Agreements and Disagreements with Other Studies or
Reviews.Te results of our meta-analysis showed that the PENG block reduces pain scores during spinal positioning placement and can reduce spinal anesthesia operation time; however, it has the same efect on the efect of pain during spinal positioning compared to FICB.Tis conclusion is consistent with Mosafa et al. [16] and controversial with Mao et al. [24].Te results of our meta-analysis are in agreement with the results of Samar Rafk Amin's metaanalysis [31], both of which believe that the PENG block can reduce pain scores during spinal positioning placement.However, this article has limitations.Hua et al. [20] and Jadon et al. [15] did not indicate that the placement time of spinal anesthesia was thirty minutes after the PENG block.
Te PENG block does not block the femoral neuromotor branch of the quadriceps muscle, which has a lesser impact on the muscle.Te results of our meta-analysis showed that the PENG block can reduce the probability of postoperative hypokinesia when compared with the FICB group, which is consistent with the fndings of Aliste et al. [5] and Hua et al. [20]; the PENG block has the same efect on muscle strength as that of the group without the nerve block.Our results concluded that the PENG block could advance the time of patients' frst time out of bed walking, further suggesting that the PENG block has less efect on the movement of the  10 International Journal of Clinical Practice quadriceps.Te results of our meta-analysis are in agreement with the results of Anwar U. Huda's meta-analysis [32], which concluded that the PENG block caused less risk of motor hindrance.However, they did not mention that patients could be active earlier after surgery.
A review showed that the use of the nerve block is not only better than general analgesia and reduces the risk of postoperative complications, but it also reduces the consumption of opioids [33], which provide adequate analgesia but can cause nausea, constipation, and delirium [34,35].Because of this, other analgesic techniques are recommended to reduce opioid consumption in the surgical management of hip fractures.Several RCTs have concluded that the postoperative PENG block reduces postoperative pain in patients, and the results of our meta-analysis showed that the PENG block reduces postoperative pain when compared to the group that did not undergo the block and that the PENG block has a comparable efect on postoperative pain in patients when compared to FICB, a fnding that is consistent with the results of a randomized controlled trial by Aliste et al. [5], while Natrajan et al. [17], Mosafa et al. [16], Senthil et al. [2], Jadon et al. [15], Hua et al. [20], and Mao et al. [24] concluded that postoperative analgesia after the PENG block was superior to FICB.Anwar U. Huda's meta-analysis [32], which included other nerve blocks, concluded that there was no signifcant diference between the PENG block and other nerve blocks.Ahmed Farag's meta-analysis [36] concluded that there was no signifcant diference in the pain scores of the PENG block relative to FICB at 6 h, 12 h, 24 h, and 48 h postoperatively; however, they concluded that the PENG block was unable to delay the time to frst postoperative remedial analgesia, a conclusion that difered signifcantly from our results.

Strength and Limitations
. Tis article has the following limitations.First of all, the small amount of literature included in some of the results may have led to imprecise results; the control group should have included some other nerve blocks to fully identify the advantages and disadvantages of the PENG block by comparing it with other nerve blocks.Tere are only a few articles on spinal anesthesia that reported pain scores during positioning, as well as studies on the operating time of spinal anesthesia, should be added.In addition, we did not explicitly limit the control group treatment in this article, and the diferent drugs given during anesthesia, the availability of other postoperative analgesia, and the use of diferent pain scales to record pain scores are all potential factors contributing to heterogeneity.

Implications for Practice.
Te PENG block can be operated in the supine position [4] and can reduce the pain during spinal positioning, thus increasing the degree of patient cooperation and facilitating the successful implementation of spinal anesthesia.Local analgesia for hip fracture surgery has traditionally used the myofascial block and femoral nerve block, but these blocks can lead to a decrease in postoperative muscle strength; the PENG block, while obtaining analgesic efects similar to those of FICB, has a negligible impact on quadriceps muscle strength because it only blocks sensory nerves such as the femoral nerve, the obturator nerve (ON), and the accessory obturator nerve (AON) [4], which is favorable for the patient's recovery of postoperative muscle strength and earlier mobility.Tis suggests that the PENG block can be used as a safe and efective regional block technique for patients undergoing hip fracture surgery.4.5.Implications for Research.In the future, the PENG block can be compared with other regional block modalities in detail to discover its advantages and disadvantages fully.To study whether the PENG block will afect the incidence of postoperative lower extremity venous thrombosis, the number of related literature is small, which can be used as the next research direction.

Figure 2 :
Figure 2: Risk of bias.(a) Risk of bias summary.Review authors' judgements about each risk of bias item for each included study.(b) Risk of bias graph.Review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3 :
Figure 3: Forest of standardized mean diferences in pain scores measured at diferent time points.Te green square represents the efect of individual studies, and the vertical lines show the corresponding 95% confdence intervals (CIs).Te black diamond refects the overall or summary efect.Te outer edges of the diamonds represent the CIs.

Figure 4 :
Figure 4: Forest of standardized mean diferences in the incidence of postoperative hypokinesia.Te blue square represents the efect of individual studies, and the vertical lines show the corresponding 95% confdence intervals (CIs).Te black diamond refects the overall or summary efect.Te outer edges of the diamonds represent the CIs.

Figure 5 :
Figure 5: Forest of standardized mean diferences in the time to frst walking.Te green square represents the efect of individual studies, and the vertical lines show the corresponding 95% confdence intervals (CIs).Te black diamond refects the overall or summary efect.Te outer edges of the diamonds represent the CIs.

Table 1 :
Characteristics of included studies.

Table 2 :
Assessment of evidence quality.
International Journal of Clinical Practice PENG block could reduce 24 h postoperative opioid consumption, and the diference was statistically significant (P < 0.05); compared with the subgroup of the no nerve block group, the PENG block could reduce 24 h postoperative opioid consumption, and the diference was statistically signifcant (P < 0.05).

Table 3 :
Subgroup analysis of pain score.

Table 4 :
Subgroup analysis of decreased muscle strength.

Table 5 :
Subgroup analysis of opioid consumption in 24 h after surgery.

Table 6 :
Subgroup analysis of frst rescue analgesia time after surgery.