The pericapsular nerve group (PENG) block versus placebo for postoperative analgesia in elective total hip arthroplasty: Study protocol for a multicenter blinded randomized controlled trial

Abstract

Background

The pericapsular nerve group (PENG) block is a novel motor-sparing regional technique for hip analgesia. We hypothesized that in patients undergoing hip arthroplasty, the PENG block is more effective in reducing postoperative pain than placebo.

Methods

In this multicenter, double-blind, randomized controlled trial, patients undergoing total hip arthroplasty received spinal anesthesia and local infiltration analgesia, along with either a PENG block or a sham block. The primary outcome was dynamic pain score (numeric rating scale 0–10) measured 3 h postoperatively on day 0. Secondary outcomes included quadriceps strength, pain scores on postoperative day 1, opioid consumption, complications, length of hospital stay, and patient-reported outcome measures.

Discussion

This is the protocol of our trial in which recruitment and data collection were conducted between 28 June 2021 and 8 November 2021. The results can be found in our published work.

Trial registration: Ethics approval was obtained from the Southern Area Local Health Network before recruiting the first patient. This trial was prospectively registered prior to initiation on 5 December 2020; URL: https://www.trialregister.nl/trial/9147. The study adhered to the Consolidated Standards of Reporting Trials guidelines and its extension for reporting patient-reported outcomes.

Background

Total hip arthroplasty (THA) remains a highly cost-effective intervention for managing advanced osteoarthritis, significantly reducing pain and enhancing patients’ quality of life. ¹ Its use is growing, particularly among older adults. In Australia alone, 32,929 procedures were performed during the period 2017–2018, equating to a national rate of 133 per 100,000 people ¹ Despite its benefits, THA is associated with substantial postoperative pain, often necessitating the use of strong pain medications, including opioids in approximately 90% of cases.^2–4

Optimizing pain control after surgery is critical as it not only improves comfort but also supports early mobilization and reduces complication risks.^5,6 A multimodal analgesic approach is commonly recommended to limit opioid exposure and related adverse effects.^2,7 Regional anesthesia plays a central role in this strategy, with techniques such as femoral nerve block, fascia iliaca block, and lumbar plexus block routinely employed. However, these methods frequently produce incomplete analgesia and impair motor function, which can delay rehabilitation efforts.^8,9

In response to these limitations, Girón-Arango et al. proposed the pericapsular nerve group (PENG) block in 2018 as a targeted approach to hip joint analgesia. ¹⁰ Administered under ultrasound guidance near the anterior inferior iliac spine, the PENG block is designed to anaesthetize the sensory articular branches of the femoral, obturator, and accessory obturator nerves. ¹¹ Preliminary clinical trials have demonstrated its potential to deliver effective pain relief while preserving quadriceps strength, thereby facilitating earlier ambulation and better recovery outcomes.^12–14

The combination of spinal anesthesia and local infiltration analgesia (LIA) is a widely used anesthetic and analgesic technique in THA. ¹⁵ Few studies have explored whether the addition of a PENG block can enhance pain control in patients already receiving LIA during THA. ¹⁶

This randomized, double-blind, controlled trial was therefore designed to evaluate the analgesic benefit of supplementing spinal anesthesia and LIA with a PENG block, using a sham procedure as the control.

The primary outcome was the pain score (numeric rating scale, 0–10) recorded 3 h after the surgery. Secondary outcomes included pain scores on postoperative day 1, quadriceps motor strength on days 0 and 1, opioid requirements, adverse events, length of hospital stay, patient satisfaction, and validated patient-reported outcome measures (PROMs). Table 1 summarizes the published literature related to the PENG block at the time of protocol formation in 2020.^{10,13,14,16,17} This is provided in Appendix 1 as part of this protocol.

Table 1.

Summary of key literature at the time of protocol formulation in 2020.

Author	Year	Type of article	NHMRC grading	Intervention	Outcome
Giron-Arango et al 10	2018	Case series, no controls	4	PENG block for hip fracture surgery including:• dynamic hip screw• hemiarthroplasty• total hip arthroplasty	Initial description of the PENG block. Case series of 5 participants with pre/post-procedure pain scores and evaluation of motor function.Results:• no motor block• median reduction dynamic pain score 7/10
Orozco et al 13	2020	Case series, no controls	4	PENG block + FN block for hip arthroscopy	Case series of 5 adult participants undergoing hip arthroscopyFollow up 48–72 hours with no post-operative opioids required and maximal pain score 1/10 on VAS
Mistry et al 14	2019	Case series, no controls	4	PENG block for hip fracture	Case series if 5 participants with hip fractures.Follow up at 15 minutes “significant pain reduction” without quadriceps weakness
Yu et al 16	2019	Case series, no controls	4	PENG Block for hip surgery	>100 performed with “significant post-operative pain control” 2 cases of quadriceps weakness following PENG block attributed to femoral nerve block due to misplaced local anaesthetic
Roy et al 17	2019	Case series, no controls	4	Hip surgeries including hip arthroplasty, dynamic hip screw and proximal femoral surgeries:• first five participants PENG block alone• second five participant PENG + LFCN block	Pain in LFCN distribution in first five participants.Improved post-operative pain management in the second five participants with no need for opiod analgesia and lower pain scoresPain scores not reported, opined consumption not reported, type of surgery not specified

PENG: pericapsular nerve group; LFCN: lateral femoral cutaneous nerve block; VAS: visual analog scale; FN: femoral nerve; NHMRC: National Health and Medical Research Council.

Methods

This prospective double-blind, multicenter randomized controlled trial was carried out at two tertiary academic teaching hospitals in Adelaide, South Australia, Flinders Medical Centre (FMC) and Noarlunga Health Services (NHS). Ethics approval was granted by the institutional review board (SALHN/HREC/292.20), and all participants provided written informed consent. The trial was prospectively registered (Netherlands Trial Register NL9147; Principal Investigator: D-Y. L; Registration Date: 25 December 2020; URL: https://www.trialregister.nl/trial/9147). The study adhered to the standard protocol items, including the Recommendations for Interventional Trials (SPIRIT) – Consolidated Standards of Reporting Trials (CONSORT) guidelines and its extension for reporting patient-reported outcomes. ¹⁸ Recruitment and data collection were conducted between 28 June 2021 and 8 November 2021. The study was conducted in accordance with the Helsinki Declaration of 1975 as revised in 2024. ¹⁹

We designed this study to investigate the effect of the PENG block compared with that of a sham (placebo) block in a randomized controlled trial format. We aimed to achieve this by randomizing participants into a two-arm, prospective, multicenter cohort study, to receive placebo or our study intervention (PENG block), along with standard care.

The participant, anesthesiologist, and surgeon will be blinded to the study medication administered. The postoperative pain team, known as the Acute Pain Service (APS), that routinely follows up all patients who have undergone THA surgery at FMC and NHS, will also be blinded. The team members will know that the participant has received a regional technique, but not whether with ropivacaine or placebo.

This study shall not influence the anesthetic or surgical technique, which is left entirely to the treating surgeon and anesthesiologist. Additional local anesthetic use will be limited and standardized to 100 mL of 0.1% ropivacaine with 1 mg of adrenaline, which is the standard practice at both institutions.

The study investigators shall not recruit or treat their own patients to prevent any possible coercion. If necessary, the anesthesiologists involved in the study shall exchange places with each other to prevent this.

The sham and PENG blocks shall use the same equipment (ultrasound, chlorhexidine skin disinfectant, and Sonoplex needle). Randomization shall occur following consent taking and participant enrolment.

On the date of commencement, no complications have been reported resulting from PENG blocks. One editorial case report describes a case of temporary quadriceps weakness following the block; ¹⁵ however, this is not considered a complication, and occurs invariably with the use of femoral nerve block, another commonly performed regional technique. Additionally, we have been performing the PENG block for hip surgeries within our department for hip fracture surgery patients for some time and have not noted any complications.

Postoperatively, each participant will be visited in the ward by the APS, which is a routine part of their care. During this ward consultation they will discuss the patient’s pain levels, pain medication use, and ability to mobilize postoperatively as part of the standard questions asked by this team. As part of this study, a study investigator shall administer a series of questionnaires postoperatively, including one or more assessing anxiety, depression, and delirium. We shall conduct a timed up and go (TUG) test. This is the time it takes for a patient stand up from a standard height armchair, walk 3 m, walk back to the chair, and sit back down.

We hypothesize that the PENG regional block is statistically significantly more effective in reducing pain and decreasing opiate consumption than placebo. Furthermore, we expect the PENG block to demonstrate further advantages, including sparing of the quadriceps muscles with no motor weakness postoperatively, thereby allowing participants to begin mobilization exercises with the physiotherapist on schedule, and achieve better pain relief than with placebo. We base these hypotheses on the limited literature published from other centers as well our own clinical experience with this regional technique, which justifies its increasing popularity.

Patient population

All adult patients aged ≥18 years presenting at these two large tertiary academic hospitals for primary elective THA under spinal anesthesia will be invited to participate in this study. To be eligible for study participation, individuals should be able to provide informed consent and reliably report symptoms to the research team.

Inclusion criteria

The inclusion criteria were as follows:

Hip arthroplasty surgery at FMC or Noarlunga Hospital;

Aged ≥18 years;

No contraindication to regional anesthesia;

Ability to give first-person consent and provide reliable feedback on symptoms, including pain scores;

Scheduled operative finishing time during standard hours, considering the availability of allied health staff, in particular physiotherapy staff who shall mobilize the patient initially;

Primary joint arthroplasty, i.e. not a revision of previously performed surgery.

Exclusion criteria

The exclusion criteria were as follows:

Aged <18 years;

Inability to give first-person consent;

Inability to give consent or participate in postoperative assessments due to dementia, cognitive impairment, and/or language barrier;

Allergy to chlorhexidine or local anesthetic;

Lack of consent from the participant for the use of regional anesthetic technique;

Contraindication to regional anesthesia or spinal anesthesia;

Revision hip arthroplasty surgery. We do not plan to include revision hip arthroplasties as these operations are typically more painful and complicated than primary hip surgeries.

We included the inability to provide first-person consent as an exclusion criterion after careful consideration. We believe that this will make our subjective pain scores and delirium, anxiety, and depression assessment outcomes optimally reliable.

Randomization and blinding

Participants will be allocated to receive either the active study intervention (PENG block) or undergo a placebo procedure (sham block) using a 1:1 randomization schedule generated via an online tool (www.sealedenvelope.com). Randomization will be performed exclusively by the principal investigator. Blinding will be maintained throughout the study: patients, perioperative nursing staff, the APS team, and surgical team will be blinded to group assignments. To preserve blinding integrity, the anesthesiologist who will perform the preoperative nerve block will not be involved in the patient’s intraoperative care or postoperative evaluation.

Nerve block procedures

Blocks will be administered after the administration of spinal anesthesia using ultrasound guidance with a 2.5–5 MHz curvilinear transducer.

PENG block (active group)

For those in the PENG block group, 20 mL of 0.5% ropivacaine (total dose: 100 mg), prepared by the performing anesthesiologist, will be used. After aseptic preparation and draping, the ultrasound probe will be positioned transversely just medial to the anterior inferior iliac spine. The medial portion of the probe will be rotated caudally to visualize the superior pubic ramus. A 100-mm Sonoplex needle will be advanced in-plane under real-time ultrasound visualization. The local anesthetic will be deposited into the fascial plane between the psoas tendon and superior pubic ramus.

Sham block (control group)

The placebo procedure will mimic the PENG block in appearance and duration. The same surface preparation, ultrasound scanning, and positioning will be applied. A blunt needle attached to a 20-mL syringe containing saline will be placed against the skin, and the operator will pause for a period that would approximate an actual block. No injection will be administered. To further preserve blinding, a small cross will be drawn using a surgical marker at the intended puncture site, regardless of whether an actual injection was administered.

Standardized anesthesia and analgesia protocol

To mirror routine clinical care and enhance external validity, all patients will be administered spinal anesthesia using isobaric 0.5% bupivacaine (dose range 10–14 mg), without the addition of intrathecal opioids. An intravenous dose of 8 mg dexamethasone will be given at the time of the nerve block.

The decision regarding surgical technique will be at the discretion of the treating orthopedic surgeon; however, LIA will be consistently used. All patients will receive 100 mL of 0.1% ropivacaine combined with 1 mg epinephrine as part of the LIA protocol.

Postoperatively, analgesia will be standardized. All patients will receive scheduled paracetamol and nonsteroidal anti-inflammatory drugs unless contraindicated. Opioids such as tramadol, oxycodone, and fentanyl will be available on an as-needed basis and will be administered by the nursing staff.

The choice of isobaric bupivacaine aligns with institutional practice, given its longer duration of action, which is suitable for the expected length of hip arthroplasty procedures.

This pragmatic study was designed with a focus on high external generalizability. All relevant concomitant care deemed necessary by the treating physicians will be permitted and recorded. Participant retention is by nature high in this randomized controlled trial (RCT) as it is limited to the short-term perioperative period.

Sample size calculation and statistical analyses

Prior to recruitment, a power analysis was conducted using Power Analysis and Sample Size (PASS) software (version 14, Kaysville, Utah, USA), using pain score data from both a preliminary pilot study and a previously published RCT involving the PENG block. In patients undergoing THA without a PENG block, average day 0 pain scores are reported as 4 out of 10. In contrast, those receiving a PENG block experience reduced pain scores, averaging 2 out of 10, with a standard deviation of 2.^12,13

Using a two-sided independent-samples t-test to detect a difference between these unpaired means, with a significance level of 0.05 and a power of 80%, the calculated sample size was 18 participants per group (36 in total). To account for the high dropout rate observed in the pilot phase, a 40% attrition buffer was included, increasing the required number to 26 per group. This was subsequently rounded up to 30 participants in each arm.

All data will be collected and analyzed with blinding maintained throughout. Statistical analyses will be conducted on an intention-to-treat basis using Statistical Package for Social Sciences (SPSS) software (version 27, IBM Corp., Armonk, NY, USA) and GraphPad Prism version 9 (GraphPad Software, La Jolla, CA, USA). Normality of continuous variables will be assessed using the Shapiro–Wilk test with graphs generated as part of this testing. Results will be reported as mean (standard deviation) for normally distributed data and as median (range) for non-normally distributed variables.

For between-group comparisons, categorical variables will be analyzed using either the chi-square test or Fisher’s exact test (for expected cell counts <10). Continuous data will be analyzed using the Mann–Whitney U test for nonparametric distributions and Student’s t-test for parametric distributions. A p-value <0.05 will be considered to indicate statistical significance. Data will be managed and secured using Research Electronic Data Capture (REDcap).

Discussion

Surgery booking and preoperative assessment

The following list outlines the step-by-step patient journey during this phase of the operative course as part of this study.

Participants who may require to undergo THA will be referred to the Department of Orthopedic Surgery.

The surgeons shall evaluate whether a participant needs to undergo THA. Informed consent will be obtained by the surgeons for the surgical procedure. The patient will be referred to the Department of Anesthesia for preoperative assessment and anesthetic consent.

Medical history will be noted by an anesthesiologist and documented as part of routine standard of care. If the participant meets the inclusion criteria, we shall discuss the trial with them and provide them with a copy of the participant information sheet (PIS). Participants who do not meet the inclusion criteria shall not be invited to participate in this study. We shall explain the study and the consent form to participants meeting the inclusion criteria and emphasize that participation is completely voluntary and will have no influence on their surgical care, adequacy or attention to detail paid during their anesthetic management, or the quality of their postoperative pain relief. Participants who choose to participate will be randomized on the day of their surgery by the principal investigator into either the control group or PENG block group using a computer-generated randomizer. The participant shall be blinded as to their allocation. They will be given the opportunity to consider and provide consent for study participation until the day of their surgery, which would be a period of 1–3 weeks on an average.

In the event of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related personnel restrictions, we shall provide an electronic copy of the PIS and conduct the baseline and follow-up questionnaires telephonically to minimize face-to-face contact. Adequate time will be given for participant consideration of participation, and discussion with family members or other parties will be encouraged.

A study investigator will administer some baseline questionnaires (listed above) and obtain a baseline pain score. A baseline TUG test will be conducted. This TUG test shall be performed by a physiotherapist in the event of coronavirus disease 2019 (COVID-19)-related personnel restrictions since physiotherapy service is part of routine standard of care, even during lockdown regulations.

The participant will be registered onto the theatre operating system (ORMIS) by the Department of Orthopedics.

To prevent potential conflicts of interest, Drs. Lin, Brown, and Morrison shall exchange places with each other to ensure that they are not the treating anesthetist for the participants from whom they have obtained consent.

Baseline measurements shall be noted, including the use of pain medications, chronic pain, and PROMs administered to the patients.

Psychosocial status will be assessed using one or more of the following: Center for Epidemiologic Studies Depression (CES-D) scale for assessing depression, Pain Anxiety Symptom Scale (PASS-20), and Pain Catastrophizing Scale (PCS).

Patient-reported outcomes will be assessed using the PROMIS instruments: 2-item Pain Self-efficacy Questionnaire (PSE-Q 2), PROMIS Depression, and PROMIS Pain Interference (PI).

Recovery assessments will be performed using the multidimensional 24-h Quality of Recovery-15 (QoR-15) questionnaire or the Brief Pain Inventory (BPI).

Figure 1 provides a timeline of the study, from the time at which surgery is scheduled through to hospital discharge (end of study).

Figure 1.

Timeline of the study.

Day 0: on the day of the surgery

The following list outlines the step-by-step patient journey during this phase of the operative course as part of this study.

If not already completed, a study investigator will administer some baseline questionnaires (listed above) and obtain a baseline pain score. A baseline TUG test will also be conducted.

A spinal anesthetic will be administered.

The patient will be randomized by the primary investigator using the online tool sealedenvelope.com, and the study team member in the operating theatre will be notified over the telephone or in person of the allocation.

The allocated block shall be performed in the operating theatre immediately before the start of the operation by a senior anesthetist who is experienced in regional techniques, has regularly conducted PENG blocks in the past, and is comfortable and familiar with the technique.

The two study interventions will be identical in terms of equipment, set-up, and personnel. In the case of the sham block, surgical drapes will be erected to obstruct the view from blinded staff and patient, the skin will be disinfected, and an ultrasound view of the PENG placement anatomy will be obtained. No invasive needle placement will be performed; instead, a cross with a standard surgical marker will be placed over the area where the block would be placed. A blunt needle with no skin penetration will be used to simulate the pressure sensation on the skin. Time to injection will be simulated with a pause.

In the case of the active intervention, draping, skin preparation, and ultrasound technique will be the same as those for the sham block. A cross will be drawn, and within the skin marking, a fine bore Sonoplex needle will be inserted before the regional block is placed.

The anesthesiologist shall place a sticker in the participant anesthetic chart, stating that the participant is part of this RCT and has received a “study block,” which could be either a placebo nerve block or PENG block with 20 mL of 0.5% ropivacaine.

Surgery will be conducted according to the discretion of the orthopedic surgeon. LIA is standardized at 100 mL of 0.1% ropivacaine with 1 mg of adrenaline. This is already standard practice across all surgeons at our institutions.

Postoperatively, the participant will be transferred to the recovery ward for at least 3 h (in keeping with the existing hip arthroplasty standard of care). In the recovery ward, additional pain relief measures may be given as required by the participant, with doses documented and pain scores obtained.

At 3 h postoperatively, a blinded anesthetist shall visit the participant in the recovery ward to obtain a participant satisfaction score and assess the quadriceps strength using the Oxford Muscle Power Grading Scale.

Day 1: in the ward on postoperative day 1

The following list outlines the step-by-step patient journey during this phase of the operative course as part of this study.

The APS team will visit the participant as part of the FMC/NHS standard of care, which is followed for every patient who has undergone THA.

They shall obtain and document information about pain scores; opiate use; adverse effects; and the use of any additional medications such as paracetamol, nonsteroidal anti-inflammatories, and antinausea medications, as part of their routine care and documentation duties during ward visits.

A study investigator/physiotherapist/APS team member shall visit the participant in the ward, conduct an examination of quadriceps strength using the Oxford Muscle Power Grading Scale, perform a TUG test, and ask the participant to report the time at which the effects of the regional block wore off.

At this time, a study investigator shall also administer questionnaires validated for and designed to determine the presence of anxiety, depression, and/or delirium. The completion of these questionnaire surveys requires approximately 30 min, and these surveys will be fitted around the participant’s postoperative schedule of physiotherapy and nursing care.

Post-hospital discharge participant document review

The following list outlines the step-by-step patient journey during this phase of the operative course as part of this study.

Following participant discharge, data shall be collected and collated from the participant notes and online patient clinical information system, specifically relating to any complications, date of discharge (length of hospital stay), any factors which delayed discharge for nonmedical reasons such as lack of availability of a rehabilitation bed and mental status of the participant on discharge, i.e. if delirium was present.

Any data that were not collected at the time of care shall be retrieved from the participant’s documents by the study investigators and added to our electronic deidentified participant database.

Data collection

The following data were collected: Demographic information. (a) Date of birth and (b) sex. General information. (a) Preoperative residential status and living arrangements; (b) preoperative mobility status; (c) general health status, medication use, and osteoporosis status; (d) mental health status, including anxiety and depression scoring; (e) preoperative pain score; (f) type, approach, and side of hip replacement; (g) weight and height (self-reported); and (g) information obtained from the PROMs questionnaires. Perioperative period and hospital stay. (a) Type of hip arthroplasty (anterior or posterior approach); (b) time, date, and duration of surgery; (c) pain score during recovery; (d) pre-, intra-, and early postoperative complications; (e) postoperative mental status (delirium); (f) postoperative quadriceps strength (ability to extend knee); (g) duration of effect of anesthesia (administered using the regional technique); (h) weight bearing, pain score and mobility status on postoperative day 1; (i) TUG test result; (j) time to mobilization with physiotherapy; (k) postoperative complications; (l); opiate requirement and use of other pain and anesthetic medication perioperatively, during recovery, and during ward stay; and (m) participant satisfaction. Variables on discharge. (a) Mental status (dementia and/or delirium) on discharge; (b) weight bearing and mobility status on discharge; and (c) length of hospital stay, and any reasons for delayed discharge such as lack of availability of rehabilitation placement.

Potential benefits and risks of participation

Participation in this study may not offer direct benefits to individual participants. However, the PENG block may offer superior pain control with fewer side effects compared with standard approaches. As the effectiveness of the PENG block in this context has not yet been conclusively established, its benefits remain investigational.

Sharing and publication of study findings

The findings from this research are expected to be shared through academic publications and professional presentations, including peer-reviewed journals and medical conferences. All data will be reported in a nonidentifiable format to protect participant privacy.

Trial status

Protocol version and date: Version 1, 21 February 2021

Date of recruitment initiation: 28 June 2021

Date of recruitment completion: 8 November 2021

As stated, recruitment was completed prior to the submission of this protocol. The delay in submission was due to a lack of funding at the time. However, funding has been secured, enabling the complete submission of this study. The findings of this study can be found in our published work. ²⁰