- Questions: Does local infiltration analgesia (LIA) when compared with placebo improve quality of recovery after anterior total hip arthroplasty (THA)?
- Findings: There were no differences in quality of recovery, pain score, opioid consumption, mobilization, or length of hospital stay between patients randomized to receive LIA with 2.5 mL/kg of 0.2% ropivacaine compared with 0.9% saline as placebo.
- Meaning: LIA did not improve quality of recovery 1 day after anterior THA.
The number of total hip arthroplasties (THAs) performed each year is projected to increase from 1.8 million in 2015 to 2.8 million in 2050,1 yet there is no consensus on the optimal analgesic regimen for this frequently performed procedure. Local infiltration analgesia (LIA) is widely used because it is simple to perform with few side effects; however, evidence of its efficacy is not convincing. Recent systematic reviews and meta-analyses reach different conclusions2–5; a 2019 review conducted for the US Agency for Healthcare Research and Quality recommends the use of LIA as part of a multimodal approach to analgesia.6
Notably, all the trials included in these systematic reviews have been in the setting of a lateral or posterior surgical approach to THA. An anterior approach, in which muscles are separated rather than cut and reattached, is being increasingly used for, among other reasons, its potential advantages in postoperative pain.7,8 Only one blinded randomized controlled trial (RCT) has investigated the effect of LIA in anterior THA, finding no significant difference in the mean numerical rating score (NRS) for pain 4 hours after surgery.9 However, this study was powered to detect a reduction in NRS of 3 and was unlikely to find a difference between groups because the measured pain scores were low.
Regardless of surgical approach, all studies of LIA in THA have used pain scores or opioid consumption as primary end points. A low pain score or opioid consumption is desirable; however, both of these may be achieved at the expense of other desirable outcomes. For example, a satisfactorily low pain score may be achieved with high-dose opioids, resulting in reduced alertness, poor mobility, and nausea. Although there are valid reasons to reduce prescription opioid use, the importance of isolated low opioid consumption as an outcome measure is unclear, in the absence of clinical or patient-reported outcomes. For these reasons, a valid, responsive, multidimensional patient-reported quality of recovery scale is preferable to comprehensively measure the clinical impact of an intervention.
We thus tested the hypothesis that LIA with 0.2% ropivacaine when compared with 0.9% saline as placebo would improve patient-reported quality of recovery measured by the Quality of Recovery-15 (QoR-15) score 1 day after anterior THA.
This was a single-center, parallel-group, randomized (1:1 allocation ratio), triple-blind, placebo-controlled trial. Ethical approval was granted by the Epworth HealthCare Human Research Ethics Committee. Written informed consent was obtained from all patients. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000844549, registered by principal investigator (N.L.T.), August 14, 2015). This manuscript adheres to the applicable Consolidated Standards of Reporting Trials (CONSORT) guidelines.10,11
The study was conducted at Epworth HealthCare, Richmond, a university-affiliated tertiary private hospital in metropolitan Melbourne, Australia. Eligible patients were 18–85 years of age undergoing primary unilateral anterior THA for osteoarthritis with a single surgeon. Patients were not eligible if they took opioids (except for codeine), tramadol, tapentadol, or gabapentinoids in the week before surgery, had an allergy or contraindication to the proposed analgesic or anesthetic technique, were American Society of Anesthesiologists physical status classification greater than III, had a body mass index >40, were pregnant, had undergone lower limb joint replacement in the preceding 6 months, were scheduled for further surgery within 90 days, or were previously enrolled in this study.
LIA Protocol and Standardized Anesthesia
Patients were randomly assigned to receive intraoperative periarticular infiltration of 0.2% ropivacaine or 0.9% saline placebo. The remainder of perioperative care (LIA and anesthetic techniques, multimodal analgesia) was identical and standardized. The LIA injectate, 2.5 mL/kg capped at 200 mL, was injected using multiple passes at each level. With the prostheses implanted and with the deep retractor deployed, half the study solution was injected into the muscles in the subfascial plane (the tensor fascia lata, anterior border of the gluteus medius, upper anterior border of vastus lateralis, and then medially into the adductors along the medial margin of the acetabulum, and finally into the rectus femoris musculature). The remaining half was infiltrated with multiple passes into the subcutaneous tissues once the deep fascia was closed.
Intravenous (IV) paracetamol (1 g) and parecoxib (40 mg) were administered intraoperatively. Immediate-release oxycodone (10 mg orally) was administered in the postanesthesia care unit. Regular postoperative analgesia was 1330 mg of oral paracetamol (modified-release) every 8 hours, 15 mg of meloxicam daily, and 10/5 mg of oxycodone/naloxone (modified release) every 12 hours (reduced to 5/2.5 mg if the patient weighed <50 kg, or increased to 20/10 mg if the patient weighed >85 kg). Immediate-release oxycodone (5–10 mg) was administered every 4 hours if the pain NRS was >2. Patients with pain NRS >7 were administered 25-µg boluses of fentanyl via IV patient-controlled analgesia.
Anesthesia comprised spinal anesthesia (12.5–15 mg of intrathecal bupivacaine and 15 µg of fentanyl) and sedation (IV midazolam and propofol titrated to participant comfort). Dexamethasone (4 mg IV) was administered intraoperatively for its anti-inflammatory and analgesic properties. Ondansetron (8 mg IV) was commenced intraoperatively and used for routine antiemetic prophylaxis given every 8 hours for 24 hours. An anterior surgical approach was used, with no wound drains or urinary catheters (unless required for urinary incontinence). IV tranexamic acid (1 g) and cefazolin (2 g) were administered intraoperatively. Patients received IV antibiotic prophylaxis for 48 hours and daily thromboprophylaxis with low molecular weight heparin (enoxaparin) for 4 weeks postoperatively. IV fluid was ceased the day after surgery if oral fluid intake had commenced and the patient was hemodynamically stable. A standardized mobilization plan and discharge criteria were in place.12
The primary outcome measure was QoR-15 score on postoperative day (POD) 1 as close to 24 hours postoperatively as feasible, with a range of 20–26 hours. QoR-15 is a valid, reliable, and responsive multidimensional patient-reported quality of recovery scale.13 Scores from 15 items that assess the domains of pain, physical comfort, physical independence, emotions, and psychological support are summed to form a composite score that ranges from 0 (extremely poor recovery) to 150 (excellent recovery). QoR-15 has undergone extensive psychometric testing and is recommended for use in trials assessing postoperative patient comfort.14
Secondary outcomes were pain, as measured by worst pain NRS (0: no pain, 10: worst imaginable) at rest and on movement in the past 24 hours on POD 1, and Brief Pain Inventory (BPI severity and interference components; 0–10, 0: no pain or interference, 10: worst imaginable pain or interference) on POD 90. BPI is a patient-reported measure that assesses pain and its interference with physical and emotional functioning, recommended for use in trials assessing chronic pain.15 Opioid consumption was measured by total oral morphine equivalent (OME, mg/d; total dose of opioid medication in the past 24 hours) on PODs 1 and 2, calculated by the Australian and New Zealand College of Anaesthetists Faculty of Pain Medicine opioid equianalgesic calculator.16 Mobilization was measured by the 10-meter walk test (10MWT; time taken for the patient to walk 10 m) on POD 1. Length of hospital stay was measured from commencement of anesthesia to time of discharge.
Randomization and Blinding
A statistician prepared a computer-generated randomization schedule using random permuted blocks. Patients were allocated to receive either 0.2% ropivacaine or 0.9% saline in a 1:1 ratio, stratified by sex (1:1.5 male-to-female ratio, in accordance with the surgeon’s usual patient sex distribution). Opaque, sealed, stapled envelopes containing the written letter “R” for 0.2% ropivacaine or “S” for 0.9% saline were placed in sequential order according to the stratified randomization schedule by a hospital pharmacist and stored in a secure office in the pharmacy department.
On request, a pharmacist opened the next envelope in the stratified group, then prepared and delivered the allocated study drug in identical sterile containers labeled with the patient’s details and “0.2% ropivacaine or 0.9% saline.” Allocation was concealed until after completion of statistical analysis. When the sample size was increased, the randomization schedule was extended in an identical manner by the randomization statistician.
All patients, clinical staff (surgeon, anesthetist, other theater and ward doctors, nurses, and physiotherapists), and research personnel (enrolling nurse and statisticians) were blinded to treatment allocation. Both 0.2% ropivacaine and 0.9% saline are clear, colorless, nonviscous, odorless solutions, and are identical in appearance.
Forty-nine patients per group were required for an expected difference in QoR-15 of 10 points, expected standard deviation (SD) of 15 points, statistical power of 0.90, and a 2-tailed α of .05. After commencement of recruitment, the developers of the QoR-15 score estimated the minimal clinical important difference to be 8 points.17 The recalculated sample size was 75 patients per group. To allow for loss to follow-up and protocol deviations, we recruited 160 patients. No interim analysis was performed, and all patients, hospital staff, and research personnel remained blinded to the allocated intervention.
All outcomes were analyzed on an intention-to-treat basis. We also report a secondary per protocol sensitivity analysis. We compared the distributions of all continuous and discrete outcome measures using the Wilcoxon rank sum test and reported the Hodges–Lehmann median difference and robust 95% confidence intervals (CIs).18 The Hodges–Lehmann estimator is the median of all pairwise differences between groups and is not necessarily equal to the difference in group medians. We compared categorical outcomes using Fisher exact test and reported frequencies and proportions. For all tests, a P value of <.05 was considered significant. Continuous or discrete baseline characteristics were described using median and interquartile range (IQR) or mean and SD as appropriate. Categorical data were summarized with frequencies and proportions. Differences between baseline characteristics were assessed by standardized differences. The standardized difference is the difference in group means or proportions scaled by the pooled SD.19 Differences <0.1 in prognostic baseline covariates were considered insignificant, and differences <0.2 were considered small. All calculations were performed in Stata Version 14 (StataCorp, College Station, TX).20
One hundred sixty patients were randomized between April 20, 2016, and August 28, 2018. Six patients were withdrawn, and complete outcome data were not available for 2 patients, resulting in the primary outcome data being analyzed in 152 patients (Figure 1). The groups were similar in baseline patient and procedural characteristics (Table 1).
The median (IQR) QoR-15 score on POD 1 of the ropivacaine group was 119.5 (102–124) compared with the placebo group, which had a median (IQR) of 115 (98–126) (Figure 2). The median difference of 2 (95% CI, −4 to 7; P = .56) was not statistically or clinically significant. Median differences of each domain of QoR-15 were not different (Table 2).
A secondary as-per-protocol sensitivity analysis included 146 patients who received spinal anesthesia without general anesthesia and the allocated intervention (2 patients were excluded in the ropivacaine group, and 4 patients were excluded in the placebo group). The results were similar. Median (IQR) QoR-15 score on POD 1 of the ropivacaine group was 119.5 (102–124.5) compared with the placebo group, which had a median (IQR) of 114.5 (98–126). The median difference of 2 (95% CI, −3 to 8; P = .48) was not statistically or clinically significant.
Worst pain NRS at rest and on movement on POD 1 (Figure 3), OMEs on PODs 1 and 2, 10MWT on POD 1, BPI interference on POD 90, and length of stay were not different (Table 2). The median (IQR) BPI severity at POD 90 in the ropivacaine group was 0.25 (0–1), compared with 0 (0–0.25) in the placebo group. This median difference (0 [0–0.25]) was statistically significant (P = .03); however, the difference was not clinically significant. The number (proportion) of patients using any opioid analgesia in the ropivacaine and placebo groups were 11 (15%) and 14 (18%) at POD 30, and 3 (4%) and 2 (3%) at POD 90. The respective risk ratios were 0.83 (95% CI, 0.40–1.7; P = .67) and 1.6 (95% CI, 0.27–9.2; P = .61).
There were no local anesthetic toxicity complications. Three patients in the ropivacaine group had superficial wound infections requiring antibiotic treatment. One patient in each group had a prosthesis infection requiring antibiotic treatment and joint washout.
There was no significant difference in the primary outcome measure, QoR-15 score on POD 1, in patients receiving 0.2% ropivacaine LIA compared with 0.9% saline as placebo. Similarly, there were no clinically significant differences between groups for secondary outcome measures of worst pain NRS at rest or with movement, opioid consumption, early mobilization, pain severity or interference on POD 90, or length of hospital stay. Our findings are consistent with the other single trial of LIA in anterior THA,9 which showed no benefit of LIA compared with placebo in pain scores at 4 hours postoperatively, or opioid consumption up to 2 days postoperatively.
Uniquely, we used a multidimensional patient-reported outcome measure of recovery for the primary end point of the study. This allowed an overall assessment of pain, physical comfort, and physical independence, rather than mandating a primary outcome of one desirable attribute over another. In a recent systematic review, QoR-15 fulfilled all criteria for measurement properties of a patient-reported outcome measure,21 that is internal consistency, reliability, measurement error, content validity (including face validity), construct validity (including structural validity, hypotheses testing, and cross-cultural validity), criterion validity, and responsiveness. It has undergone extensive validation and psychometric testing in 4 languages13,17,22–24 and orthopedic surgery,25 has been used as a primary and secondary end point in randomized26–32 and observational33,34 studies, and is recommended for use as a measure of patient comfort by the Standardized Endpoints in Perioperative Medicine (StEP) group.14
LIA was rapidly introduced into clinical practice after publication of a large case series.35 The trials that followed compared LIA with alternative analgesic techniques such as epidural analgesia36 and intrathecal morphine37,38 and found that LIA provided comparable analgesic benefit. Comparisons of multidrug LIA and placebo have demonstrated a reduction in pain scores and opioid consumption39–42; however, the methodology was suboptimal because systemic analgesia in control groups did not include nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids, both of which are known to improve postoperative pain scores. Other studies did not use a placebo, and therefore were unblinded.40,43
Rigorously conducted blinded RCTs have found that LIA is not superior to placebo in reducing pain scores44,45 or analgesic consumption46,47 after nonanterior THA. Nevertheless, while evidence in recent metanalyses and reviews2–6 for the superiority of LIA compared with placebo after nonanterior THA may be unconvincing, this is the second trial which has failed to demonstrate that LIA is superior to placebo after anterior THA.
This may be because there is limited ability of an analgesic intervention to reduce pain scores in an inherently less painful procedure (anterior THA compared with posterior or lateral THA). Another possibility is that any potential effect of LIA was short lived and therefore not detected on POD 1. If it exists, such a short-lived effect has questionable benefit. We chose QoR-15 because we wished for a comprehensive measure of recovery. Our results show no significant difference between groups for the primary outcome measure, QoR-15, nor for each individual domain of QoR-15: pain, physical comfort, physical independence, emotions, or psychological support. In addition, there was no significant difference between groups for secondary outcomes of worst NRS at rest or on movement, or opioid consumption; the study outcomes are consistent. Finally, a type 2 error (incorrectly retaining the null hypothesis) cannot be ruled out in a negative superiority trial. Because the robust 95% CI of the Hodges–Lehmann median difference in our primary outcome (QoR-15) is −4 to 7, it is very unlikely that the true difference between groups is >8, the Minimal Clinically Important Difference used in our sample size calculation.
The single-surgeon design of this study may limit generalizability of the findings. However, this ensured consistent LIA technique, which was essential. As discussed above, the findings of our study may not generalize to nonanterior THA approaches with larger incisions and different dissection techniques, or to LIA injectates other than plain 0.2% ropivacaine. Our findings may also not be applicable in institutions outside Australia with different clinical pathways. Although standard in Australia48 and potentially comparable with the United Kingdom,49 our length of stay is longer compared with the United States.50 We cannot directly compare opioid use in our trial with the other trial of LIA in anterior THA.9 However, compared with studies of LIA in nonanterior THA, our study population’s opioid consumption in the first 24 hours postoperatively was greater than that of study populations that had a spinal anesthetic with sedation44 and lower than that of study populations that had a general anesthetic.46,47
In conclusion, LIA with 0.2% ropivacaine when compared with 0.9% saline as placebo did not improve quality of recovery 1 day after anterior THA. The results of our study strengthen the evidence that LIA is not beneficial after anterior THA.
The authors acknowledge Donna McCallum, EN (Research Development Unit, Epworth HealthCare, Melbourne, Victoria, Australia) for screening and enrolling the patients and for collecting the data, and Justin Hunt, MBBS, FRCS (Musculoskeletal Institute, Epworth HealthCare, Melbourne, Victoria, Australia) for performing the surgery and local infiltration analgesia (LIA).
Name: Nicole L. Tan, MBBS, FANZCA, MClinRes.
Contribution: This author helped prepare and approve the final manuscript, and design and conduct the study.
Name: Robert Gotmaker, MBBS, FANZCA, MBiostat.
Contribution: This author helped prepare and approve the final manuscript, and perform the statistical analysis.
Name: Michael J. Barrington, MBBS, FANZCA, PhD.
Contribution: This author helped prepare and approve the final manuscript, and design and conduct the study.
This manuscript was handled by: Richard Brull, MD, FRCPC.
1. Pabinger C, Lothaller H, Portner N, Geissler A. Projections of hip arthroplasty in OECD countries up to 2050. Hip Int. 2018;28:498–506.
2. Andersen LØ, Kehlet H. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty: a systematic review. Br J Anaesth. 2014;113:360–374.
3. Højer Karlsen AP, Geisler A, Petersen PL, Mathiesen O, Dahl JB. Postoperative pain treatment after total hip arthroplasty: a systematic review. Pain. 2015;156:8–30.
4. Jiménez-Almonte JH, Wyles CC, Wyles SP, et al. Is local infiltration analgesia superior to peripheral nerve blockade for pain management after THA: a network meta-analysis. Clin Orthop Relat Res. 2016;474:495–516.
5. Yin JB, Cui GB, Mi MS, et al. Local infiltration analgesia for postoperative pain after hip arthroplasty: a systematic review and meta-analysis. J Pain. 2014;15:781–799.
6. Soffin EM, Gibbons MM, Ko CY, et al. Evidence review conducted for the agency for healthcare research and quality safety program for improving surgical care and recovery: focus on anesthesiology for total hip arthroplasty. Anesth Analg. 2019;128:454–465.
7. Barrett WP, Turner SE, Leopold JP. Prospective randomized study of direct anterior vs postero-lateral approach for total hip arthroplasty. J Arthroplasty. 2013;28:1634–1638.
8. Miller LE, Gondusky JS, Bhattacharyya S, Kamath AF, Boettner F, Wright J. Does surgical approach affect outcomes in total hip arthroplasty through 90 days of follow-up? A systematic review with meta-analysis. J Arthroplasty. 2018;33:1296–1302.
9. den Hartog YM, Mathijssen NM, van Dasselaar NT, Langendijk PN, Vehmeijer SB. No effect of the infiltration of local anaesthetic for total hip arthroplasty using an anterior approach: a randomised placebo controlled trial. Bone Joint J. 2015;97-B:734–740.
10. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.
11. Calvert M, Blazeby J, Altman DG, Revicki DA, Moher D, Brundage MD; CONSORT PRO Group. Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA. 2013;309:814–822.
12. Tan NLT, Hunt JL, Gwini SM. Does implementation of an enhanced recovery after surgery program for hip replacement improve quality of recovery in an Australian private hospital: a quality improvement study. BMC Anesthesiol. 2018;18:64.
13. Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. 2013;118:1332–1340.
14. Myles PS, Boney O, Botti M, et al.; StEP–COMPAC Group. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort. Br J Anaesth. 2018;120:705–711.
15. Dworkin RH, Turk DC, Wyrwich KW, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9:105–121.
16. Opioid Calculator [computer program]. Version 1.0. 2015.Melbourne, VIC: Faculty of Pain Medicine, ANZCA
17. Myles PS, Myles DB, Galagher W, Chew C, MacDonald N, Dennis A. Minimal clinically important difference for three quality of recovery scales. Anesthesiology. 2016;125:39–45.
18. Newson R. Confidence intervals for rank statistics: percentile slopes, differences, and ratios. Stata Journal. 2006;6:497–520.
19. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28:3083–3107.
20. Stata Statistical Software: Release 14 [computer program]. 2015.College Station, TX: StataCorp LP
21. Kleif J, Waage J, Christensen KB, Gögenur I. Systematic review of the QoR-15 score, a patient- reported outcome measure measuring quality of recovery after surgery and anaesthesia. Br J Anaesth. 2018;120:28–36.
22. Bu XS, Zhang J, Zuo YX. Validation of the Chinese version of the quality of recovery-15 score and its comparison with the post-operative quality recovery scale. Patient. 2016;9:251–259.
23. Kleif J, Edwards HM, Sort R, Vilandt J, Gögenur I. Translation and validation of the Danish version of the postoperative quality of recovery score QoR-15. Acta Anaesthesiol Scand. 2015;59:912–920.
24. Lyckner S, Böregård IL, Zetterlund EL, Chew MS. Validation of the Swedish version of quality of recovery score -15: a multicentre, cohort study. Acta Anaesthesiol Scand. 2018;62:893–902.
25. Chazapis M, Walker EM, Rooms MA, Kamming D, Moonesinghe SR. Measuring quality of recovery-15 after day case surgery. Br J Anaesth. 2016;116:241–248.
26. Cho E, Kim DH, Shin S, Kim SH, Oh YJ, Choi YS. Efficacy of palonosetron-dexamethasone combination versus palonosetron alone for preventing nausea and vomiting related to opioid-based analgesia: a prospective, randomized, double-blind trial. Int J Med Sci. 2018;15:961–968.
27. Cooke FE, Samuels JD, Pomp A, et al. A randomized, double-blind, placebo-controlled trial of intravenous acetaminophen on hospital length of stay in obese individuals undergoing sleeve gastrectomy. Obes Surg. 2018;28:2998–3006.
28. Ivry M, Goitein D, Welly W, Berkenstadt H. Melatonin premedication improves quality of recovery following bariatric surgery - a double blind placebo controlled prospective study. Surg Obes Relat Dis. 2017;13:502–506.
29. Iwanoff C, Salamon C. Liposomal bupivacaine versus bupivacaine hydrochloride with lidocaine during midurethral sling placement: a randomized controlled trial. J Minim Invasive Gynecol. 2018. In press.
30. Kleif J, Kirkegaard A, Vilandt J, Gögenur I. Randomized clinical trial of preoperative dexamethasone on postoperative nausea and vomiting after laparoscopy for suspected appendicitis. Br J Surg. 2017;104:384–392.
31. Sargant SC, Lennon MJ, Khan RJ, Fick D, Robertson H, Haebich S. Extended duration regional analgesia for total knee arthroplasty: a randomised controlled trial comparing five days to three days of continuous adductor canal ropivacaine infusion. Anaesth Intensive Care. 2018;46:326–331.
32. Xin J, Zhang Y, Zhou L, et al. Effect of dexmedetomidine infusion for intravenous patient-controlled analgesia on the quality of recovery after laparotomy surgery. Oncotarget. 2017;8:100371–100383.
33. Boissard M, Crenn V, Noailles T, Campard S, Lespagnol F. Recovery after shoulder arthroscopy: inpatient versus outpatient management. Orthop Traumatol Surg Res. 2018;104:39–43.
34. Zaballos M, Reyes A, Etulain J, Monteserín C, Rodríguez M, Velasco E. Desflurane versus propofol in post-operative quality of recovery of patients undergoing day laparoscopic cholecystectomy. Prospective, comparative, non-inferiority study. Rev Esp Anestesiol Reanim. 2018;65:96–102.
35. Kerr DR, Kohan L. Local infiltration analgesia: a technique for the control of acute postoperative pain following knee and hip surgery: a case study of 325 patients. Acta Orthop. 2008;79:174–183.
36. Andersen KV, Pfeiffer-Jensen M, Haraldsted V, Søballe K. Reduced hospital stay and narcotic consumption, and improved mobilization with local and intraarticular infiltration after hip arthroplasty: a randomized clinical trial of an intraarticular technique versus epidural infusion in 80 patients. Acta Orthop. 2007;78:180–186.
37. Kuchálik J, Granath B, Ljunggren A, Magnuson A, Lundin A, Gupta A. Postoperative pain relief after total hip arthroplasty: a randomized, double-blind comparison between intrathecal morphine and local infiltration analgesia. Br J Anaesth. 2013;111:793–799.
38. Rikalainen-Salmi R, Förster JG, Mäkelä K, et al. Local infiltration analgesia with levobupivacaine compared with intrathecal morphine in total hip arthroplasty patients. Acta Anaesthesiol Scand. 2012;56:695–705.
39. Andersen LJ, Poulsen T, Krogh B, Nielsen T. Postoperative analgesia in total hip arthroplasty: a randomized double-blinded, placebo-controlled study on peroperative and postoperative ropivacaine, ketorolac, and adrenaline wound infiltration. Acta Orthop. 2007;78:187–192.
40. Busch CA, Whitehouse MR, Shore BJ, MacDonald SJ, McCalden RW, Bourne RB. The efficacy of periarticular multimodal drug infiltration in total hip arthroplasty. Clin Orthop Relat Res. 2010;468:2152–2159.
41. Liu W, Cong R, Li X, Wu Y, Wu H. Reduced opioid consumption and improved early rehabilitation with local and intraarticular cocktail analgesic injection in total hip arthroplasty: a randomized controlled clinical trial. Pain Med. 2011;12:387–393.
42. Parvataneni HK, Shah VP, Howard H, Cole N, Ranawat AS, Ranawat CS. Controlling pain after total hip and knee arthroplasty using a multimodal protocol with local periarticular injections: a prospective randomized study. J Arthroplasty. 2007;22:33–38.
43. Dobie I, Bennett D, Spence DJ, Murray JM, Beverland DE. Periarticular local anesthesia does not improve pain or mobility after THA. Clin Orthop Relat Res. 2012;470:1958–1965.
44. Hofstad JK, Winther SB, Rian T, Foss OA, Husby OS, Wik TS. Perioperative local infiltration anesthesia with ropivacaine has no effect on postoperative pain after total hip arthroplasty. Acta Orthop. 2015;86:654–658.
45. Lunn TH, Husted H, Solgaard S, et al. Intraoperative local infiltration analgesia for early analgesia after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain Med. 2011;36:424–429.
46. Zoric L, Cuvillon P, Alonso S, et al. Single-shot intraoperative local anaesthetic infiltration does not reduce morphine consumption after total hip arthroplasty: a double-blinded placebo-controlled randomized study. Br J Anaesth. 2014;112:722–728.
47. Solovyova O, Lewis CG, Abrams JH, et al. Local infiltration analgesia followed by continuous infusion of local anesthetic solution for total hip arthroplasty: a prospective, randomized, double-blind, placebo-controlled study. J Bone Joint Surg Am. 2013;95:1935–1941.
48. Christelis N, Wallace S, Sage CE, et al. An enhanced recovery after surgery program for hip and knee arthroplasty. Med J Aust. 2015;202:363–368.
49. Burn E, Edwards CJ, Murray DW, et al. Trends and determinants of length of stay and hospital reimbursement following knee and hip replacement: evidence from linked primary care and NHS hospital records from 1997 to 2014. BMJ Open. 2018;8:e019146.
50. Molloy IB, Martin BI, Moschetti WE, Jevsevar DS. Effects of the length of stay on the cost of total knee and total hip arthroplasty from 2002 to 2013. J Bone Joint Surg Am. 2017;99:402–407.