Comprehensive Review

Postoperative pain treatment after total hip arthroplasty: a systematic review Anders Peder Højer Karlsena,*, Anja Geislerb, Pernille Lykke Petersenb, Ole Mathiesenb, Jørgen B. Dahla

Abstract Treatment of postoperative pain should rely on results from randomized controlled trials and meta-analyses of high scientific quality. The efficacy of a particular intervention may depend on the type of surgical procedure, which supports the reporting of “procedurespecific” interventions. The aim of this systematic review was to document the procedure-specific evidence for analgesic interventions after total hip arthroplasty (THA). This PRISMA-compliant and PROSPERO-registered review includes randomized placebo-controlled trials (RCTs) of medication-based analgesic interventions after THA. Endpoints were postoperative opioid consumption, pain scores (rest and during mobilization), adverse events, and length of hospital stay. Fifty-eight trials with 19 different interventions were retrieved. High risk of bias, substantial differences in assessment-tools and criteria for pain, irregular reporting of adverse events, considerable differences in supplemental analgesic consumption, and basic analgesic regimens generally characterized trials. Meta-analyses of non-steroidal anti-inflammatory drugs, local infiltration analgesia, intrathecal opioids, and lumbar plexus block provided a 24-hour intravenous morphine-sparing effect of 14.1 (95 % confidence interval: 8.0-20.2) mg, 7.5 (3.7-11.3) mg, 19.8 (14.9-24.7) mg, and 11.9 (6.4-17.3) mg, respectively. Non-steroidal anti-inflammatory drugs and lumbar plexus block were demonstrated to provide reductions in postoperative pain scores. Intrathecal opioids increased pruritus, and lumbar plexus block reduced nausea and pruritus. The GRADE-rated quality of evidence ranged from low to very low throughout the analyses. This review demonstrated, that some analgesic interventions may have the capacity to reduce mean opioid requirements and/or mean pain intensity compared with controls, but the available randomized placebo-controlled trials does not allow a designation of a “best proven intervention” for THA. Keywords: Postoperative pain management, Systematic review, Total hip arthroplasty, Non-steroidal anti-inflammatory drugs,

local infiltration analgesia, Lumbar plexus block, Intrathecal morphine

1. Introduction It is well documented that treatment of postoperative pain often remains insufficient, and there is no international consensus about the optimal analgesic intervention after most surgical procedures, including total hip arthroplasty (THA).4,5,15,27,60 The primary goal of contemporary postoperative pain treatment is to reduce pain during rest and mobilization, and, if relevant, to reduce opioid consumption and thereby opioid-related adverse effects. It is further conceived that optimal pain management may facilitate early mobilization, improve postoperative outcome, and reduce the length of hospital stay (LOS).16,44,45

There is general agreement that medical interventions must be “evidence-based,” that is, rely on results from well-conducted randomized controlled trials (RCTs) and meta-analyses of the highest up-to-date scientific quality. It has also been suggested that postoperative pain treatment should be “procedure-specific,” because the efficacy of a particular intervention may vary depending on the type of surgical procedure.41 The aim of this systematic review was to investigate the evidence for analgesic effects of procedure-specific medication-based interventions after THA.

2. Methods Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. a

Department of Anaesthesia 4231, Center of Head and Orthopaedics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, b Section of Acute Pain Management, Department of Anaesthesia 4231, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark *Corresponding author. Address: Department of Anaesthesia 4231, Center of Head and Orthopaedics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Tel.: 14550732058; fax: 14535452950. E-mail address: [email protected] gmail.com (A. P. Højer Karlsen). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.painjournalonline.com). PAIN 156 (2015) 8–30 © 2014 International Association for the Study of Pain http://dx.doi.org/10.1016/j.pain.0000000000000003

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This review is structured according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses-statement.64 The review was registered in the PROSPERO international prospective register of systematic reviews on April 23, 2014 (registration number: CRD42014009382), with amendments added on September 22, 2014.

2.1. Literature search Trials were sought in PubMed, Embase, and The Cochrane Library according to Appendix 1 (available online as Supplemental Digital Content at http://links.lww.com/PAIN/A2). The last search date was August 22, 2014. Furthermore, the PROSPECT database12 and reference lists of relevant reviews were screened for eligible clinical trials. PAIN®

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2.2. Inclusion criteria Inclusion criteria were randomized controlled trials of unilateral THA, comparing the postoperative effect of a perioperative analgesic intervention against placebo in a control group that had to receive the same baseline treatment as the intervention group. The analgesic intervention had to be initiated in the immediate perioperative period and trials had to report at least 1 of the endpoints: Opioid-sparing effect, pain at rest, and pain during mobilization, or were otherwise excluded. We excluded trials concerning hip fractures, trials including patients less than 18 years, and data published in summary clinical trials, editorials, letters, and comments. 2.3. Endpoints The primary endpoint was opioid-sparing effect of the active interventions within 24 hours postoperatively. Secondary endpoints were pain at rest and during mobilization at 6 and 24 hours postoperatively, opioid-related adverse effects, interventionassociated adverse effects as reported, and differences in LOS.

3. Data extraction Data extraction consisted of the number of enrolled patients; nature of active intervention; basic analgesic regimen (ie, the underlying analgesic treatment if any, administered similarly in the intervention and control group); type of the supplemental rescue analgesic and 24-hour cumulated dose; pain score at rest and during movement at 6 6 2 hours and 24 6 4 hours postoperatively; incidence of opioid-related adverse events (postoperative nausea and vomiting [PONV], pruritus, urinary retention, respiratory depression, constipation, sedation, and dizziness); intervention-associated adverse events as reported; documented and predefined discharge criteria; and LOS. Mean values for pain score and opioid consumption in control groups were registered and “assay sensitivity” (a trial’s ability to detect a difference between groups if there is one) was deemed low if visual analog scale (VAS) 0 to 100 mm pain was ,30 mm and/or 24-hour intravenous (i.v.) morphine consumption was ,15 mg/24 h, respectively. Two authors independently extracted data into Excel and assessed the risk of bias for each eligible article. Disagreements were solved during meetings with all authors. 3.1. Missing data Authors were contacted by e-mail in the occurrence of unclear bias domains (see bias assessment) or missing information in primary outcomes mentioned in the RCTs “Methods” section. In the case of unclear bias domains due to inadequate descriptions, corresponding authors were asked to elaborate on the parameters performed to secure low risk of bias. To prevent false confirmation of suggested measures, we used open questions such as “Please describe what measures were taken to secure allocation concealment.” 3.2. Bias assessment Bias assessment was performed using the 7-piece Cochrane bias assessment tool,36 including random sequence allocation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, incomplete outcome data, selective outcome reporting, and other potential threats to validity (including conflict of interest). Each domain was rated as low,

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high, or unclear, and the summarized risk of bias was considered low when all domains were rated as low; high when at least 1 domain was rated as high; and unclear when at least 1 domain was rated as unclear. In addition, we evaluated trial sample size as an independent contributor to bias. Based on Dechartres et al.,19 we defined a cumulated trial sample size of ,50 patients as high risk of bias, 50 to 199 as moderate risk of bias, 200 to 499 as lower risk of bias, and .499 as low risk of bias. 3.3. Data analysis 3.3.1. Handling of continuous data Continuous data for pain and opioid consumption for subgroups of 3 or more trials were analyzed using Review Manager 5.39 Any opioid consumption was converted to the equivalent dose of i.v. morphine according to Appendix 2 (http://links.lww.com/PAIN/A2). Pain scores, eg, VAS 0 to 10 and verbal numerical rating scale 0 to 10, were converted to a 0 to 100 scale. Results expressed as median, and interquartile range (IQR) or range were converted to mean and SD according to The Cochrane Handbook 7.7.3.535 or37 as appropriate. When results were presented without SD or IQR, SDs were calculated from the P value according to The Cochrane Handbook 7.7.3.335; if the P value was expressed as P , 0.05, the conservative approach P 5 0.05 was used. In trials comprising more intervention groups, these were either merged if comparable, or the control group was split if the tested interventions were different, according to The Cochrane Handbook 7.7.a.35 Depending on heterogeneity, a random or fixed-effects model forest plot was performed for continuous data in the presence of 3 or more trials considering comparable interventions, with a 95% confidence interval (CI) mean difference. Risk ratio (RR) was calculated for dichotomous data in the presence of interventions of 3 or more trials, with a 95% CI. In both dichotomous and continuous data, P values of less than 0.05 were considered statistically significant. 3.3.2. Heterogeneity Heterogeneity for morphine consumption and pain score at rest was illustrated in L’Abbe´ plots for each group of intervention.78 Furthermore, heterogeneity was tested using x2 test with significance level set at a P value of 0.10, and the heterogeneity was assessed by I2, which quantifies inconsistencies, and D2 for information size adjustments. Fixed-effect or random-effect was used according to the calculated I2. 3.3.3. Strength of evidence The risk of false-positive (type I error) and false-negative results (type II error) can derive from low information size (sum of included patients) and repeated significance testing in metaanalyses. However, conducting a trial sequential analysis (TSA) can reduce this risk.86 Trial sequential analysis integrates the heterogeneity and the number of theoretically conducted interim analyses in the calculation of threshold for statistical significance and of a priori estimated information size (APIS). For standard significance testing, the Z-score is stationary at 1.96 for P 5 0.05. In TSA, a low information size is penalized by increasing the Z-score that is, more prominent results are required to qualify as significant. A priori estimated information size is the information size that is required to consider a Z-score of 1.96 statistical significant. The difference between APIS and the current information size is the number of patients who need to be included in further trials before

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A.P. Højer Karlsen et al. 156 (2015) 8–30

definitive confirmation or disproval of the intervention effect can be made. We performed TSA for opioid consumption and pain score for each intervention that demonstrated a statistically significant difference and consisted of at least 3 RCTs. We used TSA Viewer 0.9 Beta The Copenhagen Trial Unit and followed guidelines made by The Copenhagen Trial Unit (an alpha value of 0.05 and a beta value of 0.9).83 Sensitivity to detect a mean difference was set to 10 mg morphine i.v. equivalents per 24 hours for opioid consumption and 15 mm on a VAS 0 to 100 mm scale for pain scores.46,84 3.3.4. Summary of findings To assess the quality of evidence, we used The Grading of Recommendations Assessment, Development, and Evaluation (GRADE). For each outcome, 5 separate factors were rated for quality: study limitations, inconsistent results, indirectness of evidence, imprecision, and publication bias.34 Outcome results and quality of evidence were summarized for comparison according to GRADE using GRADEpro 3.6.

4. Results 4.1. Retrieved trials Search on PubMed, Embase, and The Cochrane Library identified 3886, 4497, and 2012 citations, respectively. An initial screening by the first author removed 2066 duplicates, and further 4768 citations that clearly had no relation to the present review (eg, thrombosis prophylaxis, cemented vs cementless procedures, and ossification risk). The remaining 3561 citations were assessed on title and abstract by 2 authors individually. Two hundred forty-two trials were included for fulltext download, with 24 of these being in a language other than English. Two hundred twenty-two trials were successfully

acquired, and 164 were subsequently excluded (Appendix 3, http://links.lww.com/PAIN/A2). Thus, 58 RCTs concerning medication-based postoperative pain management after THA were included for final analysis (Fig. 1). We managed to comprise the included trials into 19 subgroups of different treatment interventions. The most frequently investigated interventions were various non-steroidal anti-inflammatory drugs (including COX2 inhibitors) (10 trials), local infiltration analgesia (LIA) (11 trials), intrathecal administration of various opioids (7 trials), and lumbar plexus block (4 trials). Eighteen trials had 2 separate interventions and 2 trials had 3 separate interventions. Baseline variables from the included trials are summarized in Table 1.

4.2. Risk of bias in included trials Bias assessment demonstrated that 45 trials contained at least 1 unclear domain (a total of 116 unclear domains), and we attempted to contact the corresponding authors by e-mail. In 3 trials, e-mail addresses were not retrievable and in 8, e-mail addresses were out of use or full. Fifteen authors answered regarding 29 unclear domains, of which 17 were resolved (2 high and 15 low). The summarized risk of bias was low in 10 trials, unclear in 11, and high in 37 (Fig. 2). Furthermore, the trial sample size implicated a high risk of bias in 17 trials, moderate in 40, and lower in 1. 4.3. Supplemental and basic analgesics The majority (37 trials) administered patient-controlled analgesia with i.v. morphine to supplement the active intervention and placebo under investigation, and reported a cumulated 24-hour consumption, whereas the remaining 22 trials used i.v. fentanyl, oxycodone, hydromorphone, meperidine, piritramide, ketobemidone, or epidural fentanyl, ropivacaine, or mepivacaine. Fifty-seven trials reported a cumulated opioid consumption over a time interval from 4 to 48

Figure 1. Flowchart of trial selection.

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Author

36/36

72 (moderate)

Erol et al.25

20/20

40 (high)

Martinez et al.58

Treatment intervention in control group



Epidural bupivacaine 0.25% 20 mL





Epidural bupivacaine 75 mg and fentanyl 100 mg



Placebo Group 2: oral pregabalin 150 mg; group 3: i.v. ketamine 0.5 mg/kg bolus, 3 mg/kg per hour until closure 1 oral pregabalin 150 mg – 80 mL saline

120 (moderate)

Zoric et al.88

29/29

58 (moderate)

LIA with 160 mg ropivacaine

Chen et al.11

48/48

96 (moderate)

Intraarticular bupivacaine 300 mg



Intraarticular saline

Lunn et al.51

24/24

48 (high)

i.v. methylprednisolone 125 mg



Saline

62 (moderate)

LIA with 100 mL mixture of ropivacaine, morphine, corticosteroids, epinephrine, cefuroxime, clonidine, unknown dose

20/21/21

Epidural None ropivacaine 0.2% 8 mg/h

Acetaminophen p.o. when VAS . 4. i.v. meperidine when persisting VAS .4 PCA morphine i.v.

Assessment Assessment of 6-hour pain of 24-hour score at rest pain score at rest

Assessment of 6-hour pain score at movement

Assessment of 24-hour pain score at movement

Length of stay, registration (significance)

Yes

Yes



















PCA morphine i.v.



Yes



Yes



i.v. acetaminophen 1 g 34, i.v. nefopam 60-120 mg/24 h i.v. parecoxib 40 mg 32, p.o. acetaminophen 0.5 g 34 Acetaminophen 2 g slow release 32, celecoxib 200 mg 32, gabapentin 300 1 600 mg Lornoxicam 8 mg 32 i.v., acetaminophen 0.5 g 34 p.o.

PCA morphine i.v.

Yes

Yes







PCA meperidine i.m.

Yes

Yes





Yes (NS)

Sufentanil 5-10 mg i.v. and oral morphine 10 mg

Yes

Yes

Yes

Yes

Yes (NS)

PCA morphine i.v.

Yes

Yes

Yes

Yes



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Pandazi et al.70

Basic analgesic Type of regimen all supplemental groups analgesic

Number 1

Epidural bupivacaine 0.25% 20 mL and dexamethasone 8 mg Epidural bupivacaine 75 mg, fentanyl 100 mg, and ketamine 30 mg i.v. ketamine 0.5 mg/kg bolus, 3 mg/ kg per hour until closure

El Gendy and Elsharnouby24

Treatment intervention in group 2

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Treatment intervention in group 1

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Number of patients intervention/ control group

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Table 1

Baseline variables.

Trial sample size (risk of bias*)

Treatment intervention in group 1 Intrathecal fentanyl 25 mg, bupivacaine 12-15 mg, and magnesium sulfate 50 mg

25/25/25

75 (moderate)

Solovyova et al.77

35/35/35

105 (moderate)

Dobie et al.20

46/46

92 (moderate)

Garg et al.31

30/30

60 (moderate)

Murphy et al.69

45/46

92 (moderate)

Anis et al.3

20/20/20

60 (moderate)

Lumbar plexus block with 15 mL bupivacaine 0.5% 1 saline

Liu et al.50

41/41

81 (moderate)

Lunn et al.52

60/60

120 (moderate)

LIA with 5 mg morphine 30 mg bupivacaine 1 mL betamethasone 0.5 mL 1:1000 epinephrine LIA with ropivacaine 0.2%, epinephrine 1.5 mg

Intrathecal fentanyl 25 mg and bupivacaine 12-15 mg and i. v. magnesium sulfate 40 mg/kg LIA with ropivacaine LIA with 0.2% 50 mL, ropivacaine 0.2% ketorolac 15 mg, 50 mL, ketorolac adrenaline 0.5 mg 15 mg, 1 saline infusion adrenaline 0.5 mg 1 infusion of ropivacaine 0.2% 5 mL/h 48 h LIA with 160 mL – 0.125% levobupivacaine Epidural fentanyl 1 – mg/kg and magnesium 75 mg LIA with 150 mg – levobupivacaine in 60 mL saline

Treatment intervention in control group

Basic analgesic Type of regimen all supplemental groups analgesic

Intrathecal fentanyl 25 mg and bupivacaine 12-15 mg

i.v. ketorolac 30 Meperidine i.m. mg 34, i.v. acetaminophen 1 g 34

Yes

Saline

Celecoxib 200 PCA mg 32, hydromorphone pregabalin 50 mg i.v. 32, acetaminophen 975 mg 34

No infiltration

Acetaminophen 1 Morphine i.v. g i.v. 34

Epidural fentanyl 1 mg/kg 60 mL saline

Lumbar plexus No block block with 15 mL bupivacaine 0.5% 1 clonidine 75 mg – Saline



Saline



Tramadol 50 mg i.v. when VAS . 4 Oral PCA morphine acetaminophen 1 i.v. g 34 and oral diclofenac 75 mg 32 – Morphine i.m.

Assessment Assessment of 6-hour pain of 24-hour score at rest pain score at rest

Assessment of 6-hour pain score at movement

Assessment of 24-hour pain score at movement

Length of stay, registration (significance)

Yes







Yes















Yes (NS)

Yes

Yes







Yes

Yes







Yes

Yes







-

Oral celecoxib 200 mg 32

PCA morphine i.v.

Yes

Yes



Yes



Acetaminophen retard 2 g, celecoxib 400 mg, gabapentin 600 mg

Sufentanil iv and oral oxycodone

Yes



Yes



Yes (NS)

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Samir et al.73

Treatment intervention in group 2

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Number of patients intervention/ control group

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Table 1 (continued) Author

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Trial sample size (risk of bias*)

Treatment intervention in group 1

Treatment intervention in group 2

PCA oxycodone Oral acetaminophen 1 g 34, oral ibuprofen 400 mg 34, LIA with ropivacaine, ketorolac, and adrenaline – PCA fentanyl i.v.

28/26

54 (moderate)

LIA catheter infusion with ropivacaine 100 mg, ketorolac 15 mg, adrenaline 1 mg at 10 and 22 h postoperatively



Saline

Wu et al.87

20/20

40 (high)



Placebo

Busch et al7

32/32

64 (moderate)



No infiltration

Acetaminophen unclear dose

Chen et al.10

45/45

91 (moderate)

i.v. dexmedetomidine 0.2 mg/kg per hour for 24 h LIA with ropivacaine 400 mg, 0.6 mL 1: 1000 epinephrine, 5 mg morphine (100 mL), 30 mg ketorolac LIA with 0.5% bupivacaine 2 mL/h



Saline

Hwang et al.38

20/20

40 (high)

Oral Meperidine i.m. acetaminophen 500 mg 34 Ketorolac, PCA morphine intervention 28.5 i.v. mg, Control 51 mg

Clarke et al.13

38/38/38

114 (moderate)

Marino et al.55

75/75/75

225 (lower) Femoral plexus block with ropivacaine bolus 0.5% 0.6 mL/kg, infuse 0.2% 0.15 mL/kg per hour 154 i.v. ketamine bolus (moderate) 0.5 mg/kg followed by 2 mg/kg per minute

79/75

Saline

Placebo

Lumbar plexus None block with ropivacaine bolus 0.5% 0.6 mL/kg, infuse 0.2% 0.15 mL/kg per hour – Saline

Preoperative 1 g acetaminophen oral, 400 mg celecoxib oral and 8 mg dexamethasone i.v. i.m. ketorolac 30 mg at 0 and 6 h

Assessment of 24-hour pain score at movement

Length of stay, registration (significance)



Yes





Yes (NS)

Yes

Yes







Yes

Yes





Yes (NS)









Yes (NS)

Yes

Yes







PCA morphine i.v.



Yes



Yes



PCA hydromorphone i.v.



Yes



Yes





Yes





Yes (NS)

PCA morphine/ oxycodone/ codeine calculated as equivalents

i.v. PCA morphine acetaminophen 1 i.v. g 34, i.v. ketoprofen 50 mg 34

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Remerand ´ et al.72

i.v. magnesium – sulfate 50 mg/kg bolus followed by 15 mg/kg per hour until end surgery Oral gabapentin 600 Oral gabapentin mg preoperative 600 mg postoperatively

Assessment of 6-hour pain score at movement

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Specht et al.79

Assessment Assessment of 6-hour pain of 24-hour score at rest pain score at rest

Number 1

Basic analgesic Type of regimen all supplemental groups analgesic

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Number of patients intervention/ control group

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Table 1 (continued) Author

Treatment intervention in group 1

Treatment intervention in group 2

Treatment intervention in control group

15/15/15

45 (moderate)

Epidural 0.25% bupivacaine 2 mL

None

Kardash et al.43

25/25

50 (moderate)

i.v. dexamethasone 40 mg

Lumbar block 0.25% 0.4 mL/ kg –

Martin et al.56

28/30

58 (moderate)

Mathiesen et al.59

40/42/38

120 (moderate)

Andersen et al.2

19/18

47 (high)

Bilir et al.6

25/25

50 (moderate)

Martinez et al.57

22/19/21

62 (moderate)

Stevens et al.81

22/22

i.v. lidocaine 1.5 – mg/kg bolus 30 min before surgery 1 infusion 1.5 mg/kg per hour until 1 h before closure Oral pregabalin 300 Oral pregabalin mg 300 mg and dexamethasone 8 mg LIA with ropivacaine – 300 mg, ketorolac 30 mg, adrenaline 0.5 mg Epidural – magnesium sulfate 50 mg bolus followed by 100 mg/ d continuous infusion i.v. parecoxib 40 mg Placebo at at induction, induction and i.v. placebo at closure, parecoxib 40 mg parecoxib 40 mg 12 at closure and 12 h postoperatively h postoperatively Fascia iliaca block – with bupivacaine 0.5% 30 mL, 1: 200,000 adrenaline, 150 mg clonidine Oral morphine 10 Oral morphine 20 mg/4 h mg/4 h

20/20/20

60 (moderate)

Assessment of 24-hour pain score at movement

Length of stay, registration (significance)



Yes

Yes



Oral PCA morphine acetaminophen i.v. 650 mg 34, oral ibuprofen 400 mg 34 – PCA morphine i.v.

Yes

Yes



Yes





Yes



Yes

Yes (NS)

Placebo

Oral PCA morphine acetaminophen 1 i.v. g 34

Yes

Yes

Yes

Yes

Yes (NS)

Placebo

Oral Oral oxycodone acetaminophen 1 g 34

Yes



Yes



Yes (NS)

Saline

PCA morphine i.v.

Assessment of 6-hour pain score at movement



Saline



Assessment Assessment of 6-hour pain of 24-hour score at rest pain score at rest

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Manoir et al.54

44 (high)

Basic analgesic Type of regimen all supplemental groups analgesic

A.P. Højer Karlsen et al. 156 (2015) 8–30

Trial sample size (risk of bias*)

Utebey et al.85

Number of patients intervention/ control group

14

Table 1 (continued) Author

Saline



PCEA-fentanyl epidural

Yes

Yes







Placebo



PCA morphine i.v.

Yes

Yes

Yes

Yes



Saline



PCA morphine i.v.

Yes

Yes







Saline



PCA morphine i.v.

Yes

Yes







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Malan et al.53

61/55/65

Manoir et al.22

93/90

Murphy et al.68

15/15/15/15

Epidural clonidine, 40 mg/h postoperatively

42 (high)

181 (moderate) 183 (moderate) 60 (moderate)

20/20/20

60 (moderate)

Camu et al.8

65/69/61

195 (moderate)

Iohom et al.40

15/14

29 (high)

Kostamovaara et al.48

19/20

39 (high)

FernandezLiesa et al.26

14/15

29 (high)

Milligan et al.62

30/27

57 (moderate)

Basic analgesic Type of regimen all supplemental groups analgesic

No clonidine

Oral PCA morphine acetaminophen 1 i.v. g 34, epidural ropivacaine 4 mg/h – PCA epidural ropivacaine and piritramide i.v.

Saline

Placebo Placebo No intrathecal morphine

i.m. saline before and during surgery placebo

placebo PCA epidural fentanyl 10 mg/ mL Intrathecal bupivacaine 5% 15 mg 1 Placebo Epidural levobupivacaine 0.125% 6 mL/h for 24 h



PCA morphine i.v. – PCA morphine i.v. Rectal diclofenac PCA morphine sodium 100 mg i.m.

Assessment Assessment of 6-hour pain of 24-hour score at rest pain score at rest

Assessment of 6-hour pain score at movement

Assessment of 24-hour pain score at movement

Length of stay, registration (significance)

Yes

Yes

Yes

Yes



Yes

Yes

















Yes

Yes







Yes

Yes









PCA morphine i.v.

Yes

Yes









PCA morphine i.v.

Yes

Yes







Spinal morphine 0.6 mg –

PCA morphine i.v. PCA epidural

Yes

Yes







Yes

Yes

Yes

Yes





PCA morphine i.v.

Yes

Yes









PCA morphine i.v.





Yes

Yes



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Akin et al1

Epidural clonidine 15 mg intraoperative 1 40 mg/h postoperatively Epidural ropivacaine – 0.2% 5 mL/h as preemptive analgesia 12 h before surgery i.v. parecoxib 20 mg i.v. parecoxib 40 32 mg 32 i.v. nefopam 20 mg – 36 Intrathecal Group 2: morphine 50 mg Intrathecal morphine 100 mg; group 3: intrathecal morphine 200 mg i.m. piroxicam 20 i.m. piroxicam 20 mg 1 h before mg during surgery surgery Oral valdecoxib 20 Oral valdecoxib mg: 2 h, 12 h, 24 h, 40 mg: 2 h, 12 h, and 36 h 24 h, 36 h Oral dexketoprofen – 25 mg PCA epidural – fentanyl 10 mg/mL 1 ropivacaine 1 mg/mL, 3 mL/h Intrathecal – bupivacaine 5% 15 mg 1 methadone 4 mg Epidural – levobupivacaine 0.125% and clonidine 8.3 mg/ mL, 6 mL/h for 24 h

Treatment intervention in control group

Number 1

21/21

60 (moderate)

Treatment intervention in group 2

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Klasen et al.47

Treatment intervention in group 1

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Trial sample size (risk of bias*)

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Dobrydnjov et al.21

Number of patients intervention/ control group

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Table 1 (continued) Author

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Treatment intervention in group 1 Lumbar plexus block with bupivacaine 0.5% 0.4 mL/kg, epinephrine 1: 200,000 Epidural infusion of ropivacaine 0.1% and 1 mg/mL sufentanil at a rate of (height in cm 2 100) 30.1 Intrathecal bupivacaine 0.5% and morphine 0.1 mg Femoral plexus block bupivacaine 0.5% 40 mL 1 epinephrine 1: 200,000 i.v. propacetamol 2 g 34 Oral ibuprofen 800 mg

Stevens et al.82

28/29

47 (high)

Kampe et al.42

15/15

30 (high)

Mendieta Sanchez et al.61

15/15

30 (high)

Fournier et al.30

20/20

40 (high)

Peduto et al.71

42/47

89 (moderate) 121 (moderate)

Dahl et al.18

48/48/25

Fletcher et al.28

20/20/20

60 (moderate)

Grace et al.33

30/30/30

90 (moderate)

Grace et al.32

30/30

60 (moderate)

Fogarty et al.29

30/30/30

90 (moderate)

Treatment intervention in group 2

Treatment intervention in control group

Basic analgesic Type of regimen all supplemental groups analgesic



Skin perforation, no placebo

i.v. propacetamol PCA morphine 2 g 33, oral i.v. ibuprofen 400 mg 33



Epidural infusion of ropivacaine 0.1% at a rate of (height in cm 2 100) 30.1





Intrathecal bupivacaine 0.5% and saline





Sham block



Placebo



Placebo

Assessment of 6-hour pain score at movement

Assessment of 24-hour pain score at movement

Length of stay, registration (significance)

Yes

Yes







PCA piritramide i.v.

Yes

Yes

Yes

Yes



PCA morphine i.v.

Yes

Yes







Morphine subcutaneously



Yes







PCA morphine i.v. Ketobemidone i.v.

Yes

Yes







Yes









Placebo



PCA morphine i.v.

Yes

Yes

Yes

Yes



Intrathecal bupivacaine 0.5% 13.75 mg



PCA morphine i.v.

Yes

Yes







Intrathecal bupivacaine 13.75 mg



PCA morphine i.v.

Yes









Placebo



PCA morphine i.v.

Yes

Yes







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Oral ibuprofen 800 mg 1 codeine 60 mg i.v. ketorolac 60 mg i.v. ketorolac preoperative 60 mg postoperatively Intrathecal Intrathecal bupivacaine 0.5% bupivacaine 13.75 mg, 0.5% 13.75 mg, morphine sulfate morphine sulfate 0.5 mg 0.5 mg, clonidine hydrochloride 75 mg Intrathecal – bupivacaine 13.75 mg and morphine 0.5 mg Intrathecal clonidine Intrathecal 75-100 mg (weight morphine 1 mg ., 75 kg)

i.m. diclofenac control 101 mg intervention 85 mg

Assessment Assessment of 6-hour pain of 24-hour score at rest pain score at rest

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Trial sample size (risk of bias*)

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Number of patients intervention/ control group

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Table 1 (continued) Author























hours postoperatively. In 8 trials, other types of opioid consumptions than morphine were successfully converted to equivalent i.v. morphine doses. Values ranged from 4.1 to 63 mg/24 h with a mean of 31 mg/24 h in the control groups, based on 45 studies. In 33 trials, supplemental opioid on request was the only analgesic administered in conjunction with the intervention/ control. In 5 trials, an NSAID was administered as basic analgesic regimen in addition to supplemental opioid. Likewise, 5 trials administered paracetamol, 7 trials a combination of NSAID and paracetamol, and 3 trials a combination of NSAID, paracetamol, and gabapentin as basic analgesia. Five trials administered other basic analgesic regimens (Table 1).

Yes PCA morphine i.v. or acetaminophen 1 g oral –



Yes PCA morphine i.v. –

Yes

Yes PCA fentanyl i.v. –

Yes

Placebo – 24 (high) 12/12 Serpell et al.75

Placebo 25/22

– 47 (high)

20/18

Laitinen et al.49 Segstro et al.74

Placebo 38 (high)

25/25 Carabine et al.9



Subarachnoidal bupivacaine 2.75 mL 0.5%, diamorphine 0.75-1 mg Epidural morphine 1 mg 1 clonidine 150 mg i.v. diclofenac 75 mg bolus 15 mg/h Rectal suppositories indomethacin 100 mg 33 Oral piroxicam 40 mg the evening before surgery 1 40 mg postoperatively 60 (moderate) 30/30 Milligan et al.63

50 (moderate)

Treatment intervention in group 1

* Risk of bias related to trial sample size with following limits: below 50: high, 50-199: moderate, 200-499: lower, above 499: low. i.v., intravenous; LIA, local infiltration analgesia; NS, not significant P.0.05; PCA, patient-controlled analgesia.

– PCA morphine i.v. Epidural morphine 1 mg





Yes Yes PCA morphine i.v. – Subarachnoidal bupivacaine 2.75 mL 0.5%

Twenty-four trials reported pain score as VAS 0 to 100; 20 trials as VAS 0 to 10; and 11 trials as numerical rating scale 0 to 10 (NRS 0-10), NRS 0 to 100, verbal numerical rating scale 0-10, boxscale 0 to 10, categorical scale 0 to 3, or visual scale 0 to 6 (Appendix 4, http://links.lww.com/PAIN/A2). When converted to VAS 0 to 100 mm equivalents (not categorical scale 0-3 or visual scale 0-6), values at rest and during mobilization ranged from 4 to 67 mm and 3 to 74 mm in the control groups, respectively. The mean postoperative pain scores in control groups at 6 and 24 hours rest were 31 mm and 23 mm, respectively. Pain at rest was reported in 42 trials at 6 hours and in 47 trials at 24 hours postoperatively (Appendix 4, http://links.lww.com/PAIN/A2). Only 12 and 16 trials reported pain during movement at 6 hours and 24 hours, respectively. Ten trials reported pain during movement at both 6 and 24 hours; thus, 18 trials reported pain during movement at any time (Appendix 4, http://links.lww.com/ PAIN/A2). Because of infrequent registration, meta-analyses were not feasible for pain during movement. 4.5. Other endpoints

Trial sample size (risk of bias*) Author

17

4.4. Pain scores



Treatment intervention in control group

Basic analgesic Type of regimen all supplemental groups analgesic

Assessment Assessment of 6-hour pain of 24-hour score at rest pain score at rest





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Number of patients intervention/ control group

Treatment intervention in group 2

Table 1 (continued)

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Forty-two trials reported vomiting, nausea, or both, 14 reported sedation, 5 reported dizziness, and 11 reported pruritus (Appendix 4, http://links.lww.com/PAIN/A2). Eleven trials reported LOS, and of these, 7 had clearly predefined discharge criteria. No trial before 2007 reported LOS, and no intervention demonstrated a statistically significant reduction in LOS. Twenty-one trials had low assay sensitivity for pain score (ie, no scores above 30 mm in control groups). Four trials had low assay sensitivity for morphine consumption (ie, morphine consumption below 15 mg i.v. morphine equivalents/24 h in control groups). 4.6. Results related to specific interventions 4.6.1. Non-steroidal anti-inflammatory drugs Ten trials tested an NSAID (including COX2 inhibitors) as an intervention.1,8,18,28,40,49,53,57,74,75 One trial tested the intervention in conjunction with a basic analgesic regimen.40 The risk of bias was low in 1 trial, unclear in 1, and high in 8 (Fig. 2), and the trial sample size implicated a high risk of bias in 4 trials and a moderate risk in 6. L’Abbe´ plots demonstrated a high degree of heterogeneity for morphine consumption and a lower degree for pain scores (Appendix 5-7, http://links.lww.com/PAIN/A2). Meta-analyses demonstrated a statistically significant morphinesparing effect of 14.1 mg/24 h (95% CI: 8.0-20.2 mg) and a statistically significant reduction in pain scores at rest of 14 (10-17) and 9 (2-16) mm at 6 and 24 hours postoperatively, respectively (Figs. 3-5).

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In TSA, reductions in both morphine consumption, and 6- and 24-hour pain scores at rest, were above the threshold for significance. A priori estimated information size was reached for 6-hour pain score indicating that enough patients have been included to draw conclusions about the early analgesic effect (Appendix 8, http://links.lww.com/PAIN/A2). Meta-analyses demonstrated no significant effect on opioid-related adverse events, or adverse events related to the interventions per se (Appendix 9, http://links.lww.com/PAIN/A2). Quality of evidence (GRADE) was low for the opioid-sparing effect and reduction in 6-hour pain score, and it was very low for 24-hour pain score. Results are summarized in Table 2. Trials were too heterogeneous (time of administration, specific drugs, oral/i.v. administration) to provide information about optimal drug and dose regimens. 4.6.2 Local infiltration analgesia Eleven trials tested administration of various local infiltration regimens2,7,10,11,20,50,51,69,70,77,88 (Appendix 4, http://links.lww. com/PAIN/A2). All 11 trials tested the intervention in conjunction with basic analgesic regimens (Table 1). Two, 6, and 3 trials were of low, unclear, or high risk of bias, respectively (Fig. 2), and trial sample sizes implicated a high risk of bias in 1 trial and a moderate risk in 10. L’Abbe´ plots demonstrated a high degree of heterogeneity for both morphine consumption and pain scores (Appendix 5-7, http://links.lww. com/PAIN/A2). Meta-analyses demonstrated a statistically significant morphine-sparing effect of 7.5 (3.7-11.3) mg/24 h, and insignificant reductions in pain scores at all time points (Figs. 3-5). In TSA, reduction in morphine consumption was above the threshold for significance, and pain scores were below the threshold. A priori estimated information size was reached for morphine consumption, indicating that enough patients have been included to draw conclusions about the opioid-sparing effect. A priori estimated information size was reached for the absent effect on 24-hour pain score indicating that further testing of this endpoint is futile (Appendix 10, http://links.lww.com/PAIN/ A2). Reduced postoperative blood loss was demonstrated in one trial (P , 0.05)70; however, no differences in opioid-related adverse effects were demonstrated (Appendix 9, http://links.lww. com/PAIN/A2). Quality of evidence (GRADE) was low for the opioid-sparing and pain-relieving effects. Results are summarized in Table 2. It should be noted that different combinations of drugs were administered for LIA: in addition to local anesthetics, 2 trials included ketorolac,2,77 2 trials morphine and corticosteroids,50,70 and 1 trial morphine and ketorolac.7 None of these trials were controlled for the systemic analgesic effect that may have occurred after administration in the LIA combinations. Trials were too heterogeneous to provide information about optimal drug and dose regimens. 4.6.3 Intrathecal administration of opioids

Figure 2. Risk of bias in included studies. Green plus is low risk, yellow question mark is unclear risk, and red minus is high risk of bias.

Seven trials tested intrathecal administration of various opioids (morphine29,32,33,61,68; diamorphine63; methadone26). One trial tested the intervention in conjunction with a basic analgesic regimen (diclofenac68). One and 6 trials were of unclear and high risk of bias, respectively (Fig. 2), and the trial sample size implicated a high risk of bias in 3 trials and a moderate risk in 4. L’Abbe´ plots demonstrated a lower degree of heterogeneity for both morphine

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Figure 3. Forest plot displaying mean difference in 0- to 24-hour morphine consumption for each major intervention. Green squares with horizontal lines depict mean differences and 95% confidence intervals (CIs) for each trial. Black tiles depict the mean difference of each intervention.

consumption and pain scores (Appendix 5-7, http://links.lww. com/PAIN/A2). Meta-analysis demonstrated a statistically significant morphine-sparing effect of 19.8 (14.9-24.7) mg/24 h and insignificant reductions in pain scores at all time points (Figs. 3-5). In TSA, reduction in morphine consumption was above the threshold for significance, and pain scores were below the threshold for significance (Appendix 11, http://links.lww.com/ PAIN/A2). A priori estimated information size was not reached for morphine consumption. An increase in RR of 6.6 (2.7-16.4) was demonstrated for pruritus (Appendix 9). Quality of evidence (GRADE) was very low for the opioidsparing effect and reduction in pain scores and was low for

increases in PONV and pruritus. Results are summarized in Table 2. Trials were too heterogeneous to provide information about optimal drug and dose regimens. 4.6.4. Lumbar plexus block Four trials tested lumbar plexus block as an intervention.3,55,82,85 Two trials tested the intervention in conjunction with basic analgesic regimens (ketorolac55; propacetamol 1 ibuprofen82). All 4 trials were of high risk of bias (Fig. 2), and the trial sample size implicated a high risk of bias in 1 trial, a moderate risk in 2, and a lower risk in one. L’Abbe´ plots demonstrated a high degree of heterogeneity for both morphine consumption and pain scores

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Figure 4. Forest plot displaying the mean difference in pain scores 6-hour postoperatively for each major intervention. Green squares with horizontal lines depict mean differences and 95% confidence intervals (CIs) for each trial. Black tiles depict the mean difference of each intervention.

(Appendix 5-7, http://links.lww.com/PAIN/A2). Meta-analyses demonstrated a statistically significant morphine-sparing effect of 11.9 (6.4-17.3) mg/24 h and a statistically significant 11 (3-19) mm reduction in pain score at rest at 24 hours postoperatively (Figs. 3-5). In TSA, reductions in morphine consumption and pain score at 24 hours were above the threshold for significance; however, APIS were not reached, indicating that inclusion of more patients is necessary to draw conclusions about the extent of the analgesic effect (Appendix 12, http://links.lww.com/PAIN/A2). A reduction in RR for PONV of 0.19 (0.1-0.35) and a reduction in pruritus of (RR 0.13 [0.02-0.98]) were demonstrated (Appendix 9, http://links.lww.com/PAIN/A2). One trial demonstrated a partial or moderate motor block in the majority of patients.55 Quality of evidence (GRADE) was very low for both the opioid-sparing and pain-relieving effects, and was low for PONV and pruritus. Results are summarized in Table 2. Too few trials were available to provide information about optimal drug and dose regimens.

4.6.5. Qualitative analyses Results from a number of other interventions have been published in the literature: oral morphine54; i.v. propacetamol71; i.v. or epidural corticosteroids24,43,51,59; i.v. lidocaine56; i.v. nefopam22; i.v. or epidural ketamine25,58,72; i.v. dexmedetomidine87; gabapentin13; pregabalin58,59; i.v., intrathecal, or epidural magnesium6,31,38,73; epidural bupivacaine,85 ropivacaine,70 or ropivacaine 1 opioid42,47,48; epidural or intrathecal clonidine9,21,29,62; femoral nerve block30,55; fascia iliaca block81; and wound catheter infusion subsidiary to LIA.79 Twelve interventions were tested in conjunction with a basic analgesic regimen (Appendix 4). Seven of the above trials had a low risk of bias, 3 had unclear risk of bias, and 16 had high risk of bias. All interventions except intrathecal clonidine, femoral nerve block, i.v. lidocaine, and gabapentin demonstrated some effect on supplemental analgesic consumption and/or pain scores. Three trials demonstrated an effect on opioid-related adverse events (reduction in nausea in patients treated with dexamethasone43 and

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Figure 5. Forest plot displaying mean difference in pain scores 24-hour postoperatively for each major intervention. Green squares with horizontal lines depict mean differences and 95% confidence intervals (CIs) for each trial. Black tiles depict the mean difference of each intervention.

reduced pruritus for both femoral nerve block and epidural ketamine [P , 0.05].25,55) Qualitative data are reported in Table 3.

5. Discussion We identified 4 major groups of procedure-specific analgesic interventions for pain treatment after THA: non-steroidal antiinflammatory drugs including COX2 inhibitors, LIA, intrathecal opioids, and lumbar plexus block. Furthermore, trials reporting 15 other interventions were retrieved. These 4 groups of most reported interventions, except LIA, all demonstrated a morphine-sparing effect of at least 10 mg in forest plots, and all were confirmed in TSA. To reach APIS, however, TSA suggest a need for further inclusion of 652, 209, and 194 patients in the NSAID, intrathecal opioid, and lumbar plexus block-intervention groups, respectively. LIA demonstrated a 7.5 mg reduction in morphine consumption that was confirmed

in TSA, and APIS was reached. This reduction may however be clinically questionable. Furthermore, significant reductions in pain scores were demonstrated in TSA with a sensitivity of 15 mm for NSAID at 6 and 24 hours postoperatively. The overall evidence is, however, flawed by a number of serious limitations. Thus, the summarized risk of bias was high in 37 trials, unclear in 11, and low in only 10 trials. A substantial number of trials included small sample sizes. The observed high or unclear summarized risk of bias, together with small sample sizes, may have overestimated intervention effects. The retrieved trials demonstrated substantial differences in tools and criteria for pain assessment, as well as pronounced heterogeneity in primary outcomes. Pain scores in control groups ranged from 3 to 74 mm on a 0 to 100 mm VAS-score, and 0- to 24-hour morphine consumption ranged from 5 to 63 mg. Even in control groups that received identical basic analgesic treatment, substantial heterogeneity was displayed for both opioid

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Table 2

Summarized outcomes in Grading of Recommendations Assessment, Development, and Evaluation (GRADE) (mean difference and 95% confidence interval are provided together with quality of evidence). Summary of findings NSAID compared with placebo for pain after THA Patient or population: pain after THA Settings Intervention: NSAID Comparison: placebo Outcomes

Anticipated absolute effects* (95% CI) Risk with placebo

Risk with NSAID

Morphine consumption: assessed within 0-24 h postoperatively Pain score 4-8 h postoperatively: assessed with VAS 0-100

The mean morphine consumption The mean morphine consumption in the control group was 42.2 mg in the intervention group was 14.1 lower (20.2 lower to 8 lower) The mean pain score 4-8 h The mean pain score 4-8 h postoperatively in the control group postoperatively in the intervention was 27 mm group was 14 lower (17 lower to 10 lower) Pain score 20-28 h The mean pain score 20-28 h The mean pain score 20-28 h postoperatively: assessed with postoperatively in the control group postoperatively in the intervention VAS 0-100 was 22 mm group was 9 lower (16 lower to 2 lower) PONV: assessed with number Study population: 323 per 1000 Study population: 316 per 1000 of events (255-390) Sedation: assessed with Study population: 175 per 1000 Study population: 113 per 1000 number of events (52-241) Dizziness: assessed with Study population: 57 per 1000 Study population: 38 per 1000 number of events (11-138) Pruritus: assessed with number Study population: 0 per 1000 Study population: 0 per 1000 of events (0-0)

Relative effect (95% CI)

No. of participants Quality of the (studies) evidence (GRADE)



634 (7 RCTs)

⊕⊕⊖⊖ LOW†‡



369 (7 RCTs)

⊕⊕⊖⊖ LOW†§



296 (6 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§

785 (9 RCTs)

⊕⊕⊖⊖ LOW†‡

169 (3 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§

RR 0.98 (0.79-1.21) RR 0.65 (0.3-1.38) RR 0.67 (0.19-2.41) Not estimable

201 (1 RCT)

⊕⊕⊖⊖ LOW†‡§

(0 studies)

†‡§

Relative effect (95% CI)

No. of participants Quality of the (studies) evidence (GRADE)

Summary of findings Local infiltration analgesia compared with placebo for pain after THA Patient or population: pain after THA Settings Intervention: local infiltration analgesia Comparison: placebo Outcomes

Anticipated absolute effects* (95% CI) Risk with placebo

Morphine consumption: assessed within 0-24 h postoperatively Pain score 4-8 h postoperatively: assessed with VAS 0-100

Risk with local infiltration analgesia

The mean morphine consumption The mean morphine consumption in the control group was 24.1 mg in the intervention group was 7.5 lower (11.3 lower to 3.7 lower) The mean pain score 4-8 h The mean pain score 4-8 h postoperatively in the control group postoperatively in the intervention was 39 mm group was 8 lower (18 lower to 1 higher) Pain score 20-28 h The mean pain score 20-28 h The mean pain score 20-28 h postoperatively: assessed with postoperatively in the control group postoperatively in the intervention VAS 0-100 was 38 mm group was 3 lower (8 lower to 1 higher) PONV: assessed with number Study population: 273 per 1000 Study population: 256 per 1000 of events (185-357) Sedation: assessed with: Study population: 0 per 1000 Study population: 0 per 1000 number of events (0-0) Dizziness: assessed with: Study population: 0 per 1000 Study population: 0 per 1000 number of events (0-0) Moderate: 500 per 1000 Moderate: 0 per 1000 (0-0) Pruritus: assessed with number Study population: 22 per 1000 Study population: 22 per 1000 of events (2-346)



559 (8 RCTs)

⊕⊕⊖⊖ LOW†‡



589 (7 RCTs)

⊕⊕⊖⊖ LOW†‡



502 (5 RCTs)

⊕⊕⊖⊖ LOW†‡

396 (5 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§

90 (1 RCT)

⊕⊕⊖⊖ LOW‡§

0 studies

†‡§

91 (1 RCT)

⊕⊕⊖⊖ LOW‡§

RR 0.94 (0.681.31) RR 1 (0.0249.33) Not estimable

RR 1.02 (0.0715.9)

(continued on next page)

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Table 2 (continued) Summary of findings Intrathecal opioids compared with placebo for pain after THA Patient or population: pain after THA Settings Intervention: intrathecal morphine and bupivacaine Comparison: placebo Outcomes

Anticipated absolute effects* (95% CI) Risk with placebo

Relative effect Risk with intrathecal morphine (95% CI) and bupivacaine

Morphine consumption: assessed within 0-24 h postoperatively Pain score 4-8 h postoperatively: assessed with VAS 0-100

The mean morphine consumption The mean morphine consumption in the control group was 29.6 mg in the intervention group was 19.8 lower (24.7 lower to 14.9 lower) The mean pain score 4-8 h The mean pain score 4-8 h postoperatively in the control postoperatively in the intervention group was 21 mm group was 13 lower (26 lower to 1 higher) Pain score 20-28 h The mean pain score 20-28 h The mean pain score 20-28 h postoperatively: assessed with postoperatively in the control postoperatively in the intervention VAS 0-100 group was 6 mm group was 1 higher (2 lower to 3 higher) PONV: assessed with number Study population: 448 per 1000 Study population: 493 per 1000 of events (395-614) Sedation: assessed with Study population: 444 per 1000 Study population: 400 per 1000 number of events (244-649) Dizziness: assessed with Study population: 0 per 1000 Study population: 0 per 1000 number of events (0-0) Pruritus: assessed with Study population: 30 per 1000 Study population: 200 per 1000 number of events (82-497)

No. of participants Quality of the evidence (studies) (ssGRADE)



359 (7 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§



299 (6 RCTs)

⊕⊖⊖⊖ VERY LOW†§



299 (6 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§

360 (7 RCTs)

⊕⊕⊖⊖ LOW†§

90 (2 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§

0 studies

†‡§

360 (7 RCTs)

⊕⊕⊖⊖ LOW†§

RR 1.1 (0.88 to 1.37) RR 0.9 (0.55 to 1.46) Not estimable RR 6.6 (2.7-16.4)

Summary of findings Lumbar plexus block compared to placebo for pain after THA Patient or population: pain after THA Settings Intervention: lumbar plexus block Comparison: placebo Outcomes

Anticipated absolute effects* (95% CI) Risk with placebo

Morphine consumption: assessed within 0-24 h postoperatively Pain score 4-8 h postoperatively: assessed with VAS 0-100

Relative effect Risk with lumbar plexus block (95% CI)

The mean morphine consumption The mean morphine consumption in the control group was 44.6 mg in the intervention group was 11.9 lower (17.3 lower to 6.4 lower) The mean pain score 4-8 h The mean pain score 4-8 h postoperatively in the control group postoperatively in the intervention was 49 mm group was 31 lower (73 lower to 11 higher) Pain score 20-28 h The mean pain score 20-28 h The mean pain score 20-28 h postoperatively: assessed with postoperatively in the control group postoperatively in the intervention VAS 0-100 was 35 mm group was 11 lower (19 lower to 3 lower) PONV: assessed with number Study population: 640 per 1000 Study population: 122 per 1000 of events (64-224) Sedation: assessed with Study population: 0 per 1000 Study population: 0 per 1000 number of events (0-0) Dizziness: assessed with Study population: 589 per 1000 Study population: 665 per 1000 number of events (813-907) Pruritus: assessed with number Study population: 107 per 1000 Study population: 14 per 1000 of events (2-105)

No. of participants Quality of the (studies) evidence (GRADE)



297 (4 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§



117 (2 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§



267 (3 RCTs)

⊕⊖⊖⊖ VERY LOW†‡§

150 (1 RCT)

⊕⊕⊖⊖ LOW†§

0 studies

†‡§

253 (0 studies)

†‡§

150 (1 RCT)

⊕⊕⊖⊖ LOW†§

RR 0.19 (0.1-0.35) not estimable RR 1.13 (1.38-1.54) RR 0.13 (0.02-0.98)

CI, confidence interval; NSAID, Non-steroidal anti-inflammatory drugs; OR, odds ratio; PONV, postoperative nausea and vomiting; RR, risk ratio; THA, total hip arthroplasty. GRADE Working Group grades of evidence: (1) High quality: we are very confident that the true effect lies close to that of the estimate of the effect. (2) Moderate quality: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. (3) Low quality: confidence in the effect estimate is limited; The true effect may be substantially different from the estimate of the effect. (4) Very low quality: we have very little confidence in the effect estimate; The true effect is likely to be substantially different from the estimate of effect. * The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). † There were studies of unclear and high summarized risk of bias. ‡ There was heterogeneity as noted by I2. § There were fewer than 400 participants in total.

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Table 3

Qualitative analysis of other interventions.

Lunn et al.51

Kardash et al.43 Pandazi et al.70

Klasen et al.47

Kostamovaara et al.48 Utebey et al.85

Kampe et al.42

Dobrydnjov et al.21

Basic analgesic regimen

Treatment effect on analgesic requirement

Methylprednisolone 125 Acetaminophen 2 g oral NS, p 5 0.27 mg i.v. 32 1 celecoxib 200 mg oral 32 1 gabapentin 300 1 600 mg oral Epidural dexamethasone – Patients received both i. 8 mg adjuvant to v. meperidine and p.o. bupivacaine acetaminophen. Both were significantly reduced in the intervention group, P # 0.001 Dexamethasone 40 mg i. Acetaminophen 650 mg NS v. oral 1 ibuprofen 400 mg oral 34 Epidural ropivacaine Acetaminophen 0.5 mg Significantly reduced 0.2% 4 mL/h 34 oral 1 lornoxicam 8 from 16 to 6 mg (intervention group 2) mg 32 i.v. morphine 0-24 h, P , 0.05 Epidural ropivacaine – Significantly reduced 0.2% 10 mL/h from 284 to 188 mg patient-controlled analgesia–epidural ropivacaine 0-24 h, P 5 0.0013 Epidural ropivacaine as – NS adjuvant to fentanyl Epidural bupivacaine – Significantly reduced 0.25% 2 mL from 21.1 to 12.5 mg (intervention group 1) morphine 0-24 h, P 5 0.001 Epidural sufentanil 1 mg/ – Significantly reduced mL adjuvant to from 46 to 9 mg ropivacaine at a rate of piritramide i.v. 0-24 h, (height in cm 2 100) P , 0.001 30.1 Epidural clonidine Acetaminophen 1 g 34 Significantly reduced infusion 40 mg/h 2/1 oral 1 epidural from 29 to 17.5 and 13.5 intraoperative 15 mg ropivacaine 4 mg/h mg morphine 0-24 h, P , 0.05

Highest level of postoperative pain in control group (VAS, 0-100 mm) (assay sensitivity)

Treatment effect on pain score at 6 h postoperatively

Treatment effect on pain score at 24 h postoperatively

Length of hospital stay*

PONV†

Sedation Dizziness

40 mm at 6-h rest

Significantly reduced at Significantly reduced at both rest and movement, movement, but not at P , 0.01 rest, P , 0.01

NS

NS





55 mm at 24-h movement

Significantly reduced at Significantly reduced at both rest and movement, both rest and movement, P 5 0.02 or P , 0.0001 P 5 0.04



NS





NS



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Reference

68 mm at 24-h movement 30 mm at 6/24-h movement

NS

Significantly reduced at movement P , 0.001, but not at rest Significantly reduced at Significantly reduced at rest and movement, P , movement P , 0.05, but 0.05 not at rest



Significantly reduced nausea, P 5 0.05



NS





44 mm at 24-h rest

NS

NS









23 mm at 24-h movement 26 mm at 6-h movement

NS

NS



NS





NS

NS









0 mm (in both control and intervention group at all registrations)

NS

NS



NS

NS



25 mm at 24-h movement

NS

Significantly reduced in both groups at 24 h movement but not at rest, P , 0.05



NS





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Basic analgesic regimen



Manoir et al.54 Morphine 10 or 20 mg oral every 4 h



Erol et al.25

Martinez et al.58

Remerand ´ et al.72

Samir et al.73

Hwang et al.38

Epidural ketamine 30 mg – adjuvant to bupivacaine and fentanyl Ketamine 0.5 mg/kg i.v. – 1 3 mg/kg per hour until closure (intervention group 1) Ketamine 0.5 mg/kg i.v. Acetaminophen 1 g i.v. 1 2 mg/kg per minute 34 1 ketoprofen 50 mg continuous infusion i.v. 34

Significantly reduced from 34.9 to 13.9 mg morphine 0-24 h, P , 0.01 NS

9 mm at 6-h passive movement

NS

NS



Lower incidence of nausea in intervention group





25 mm at 6-h rest

NS

NS, mean pain score was lower in control group



NS





Significantly reduced – from 15.9 to 9.3 mg morphine 0-24 h, P , 0.05 Significantly reduced 40 mm at 6-h rest from 33 to 19 mg morphine 0-24 h for 20 mg oral administration, P 5 0.04 NS –







NS





NS

NS



NS

NS









NS





48 mm at 24-h movement



Increased in intervention group at rest



NS

NS

NS

15 mm at 24-h rest



NS

NS

NS





Significantly reduced from 77 to 52 mg morphine 0-48 h, P , 0.001 Significantly reduced from 19 to 14 mg morphine 0-24 h, P 5 0.004 Intrathecal magnesium Acetaminophen 1 g i.v. Significantly reduced sulfate 50 mg (group 1) 34 1 ketorolac 30 mg i. from 21.3 to 15.6 and or magnesium sulfate 40 v. 34 15.3 mg morphine 0-24 mg/kg (group 2) adjuvant h, respectively, P , 0.05 to intrathecal fentanyl and bupivacaine Epidural magnesium 75 – Significantly reduced mg adjuvant to fentanyl from 21.5 to 11.5 mg morphine 0-24 h, P , 0.001 Magnesium 50 mg/kg 1 Ketorolac 28.5 mg Significantly reduced 15 mg/kg per hour i.v. from 23.8 to 13.3 mg until end of surgery morphine 0-24 h, P , 0.05

Length of hospital stay*

PONV†

Sedation Dizziness

50 mm at 6-h rest

Significantly reduced at NS for both intervention rest for both intervention groups groups, P , 0.05



NS





62 mm (intervention group) at 6-h rest

Significantly increased at rest

NS



NS

NS



52 mm at 6-h rest

Significantly reduced at rest, P , 0.05

Significantly reduced at rest, P , 0.05



NS





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Treatment effect on pain score at 24 h postoperatively

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Fogarty et al.29 Intrathecal clonidine 75100 mg (intervention group 1) Carabine Epidural clonidine 150 et al.9 mg adjuvant to morphine

Treatment effect on pain score at 6 h postoperatively

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Highest level of postoperative pain in control group (VAS, 0-100 mm) (assay sensitivity)

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Table 3 (continued) Reference

(continued on next page) 25

Copyright Ó 2014 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.

Epidural magnesium 50 mg 1 100 mg/d

Basic analgesic regimen



Fournier et al.30 Stevens et al.81

Femoral nerve block with Diclofenac 100 mg i.m. bupivacaine and epinephrine Fascia iliaca plexus block – with bupivacaine, adrenaline, and clonidine

Martin et al.56 Lidocaine 1.5 mg/kg 1 1.5 mg/kg per hour i.v. intraoperative Peduto et al.71 Propacetamol 2 g 34 i. v.

Clarke et al.13

Martinez et al.58

Mathiesen et al.59

Manoir et al.54

Wu et al.87





Highest level of postoperative pain in control group (VAS, 0-100 mm) (assay sensitivity)

Significantly reduced from 437 to 328 mg epidural fentanyl 0-24 h, P , 0.05 Significantly reduced from 62.6 to 40 mg morphine 0-24 h, P , 0.05 NS

48 mm at 6-h rest

NS

NS



NS

NS



64 mm at 24-h movement



Significantly reduced at rest and movement, P , 0.05



NS





20 mm at 24-h rest



NS









34 mm at 6-h rest

NS, P 5 0.09

NS, P 5 0.38



NS





Significantly reduced from 41.5 to 23 mg morphine 0-24 h, P , 0.001 NS, P 5 0.54

Treatment effect on pain score at 24 h postoperatively

Length of hospital stay*

PONV†

Sedation Dizziness

53 mm at 24-h movement



NS

NS







29 mm at 6-h rest

NS

NS



NS





39 mm at 24-h movement



NS



NS

NS

NS

48 mm at 24-h movement



Increased in intervention group at rest



NS

NS

NS

32 mm at 24-h movement

NS

NS

NS

NS





29 mm at 6-h rest

NS

NS



NS

NS



15 mm at 6-h rest

Significantly reduced at rest, P , 0.01

Significantly reduced at rest, P , 0.05



NS



NS

(continued on next page)

Copyright Ó 2014 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.

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Significantly reduced from 17.6 to 9.4 mg morphine 0-24 h, P , 0.001 Gabapentin 600 mg oral Acetaminophen 1 g oral, NS preoperative or celecoxib 400 mg and postoperative dexamethasone 8 mg i.v. preoperative Pregabalin 150 mg oral – Significantly reduced (intervention group 2) from 77 to 44 mg morphine 0-48 h, P , 0.001 Pregabalin 300 mg oral Acetaminophen 1 g 34 Significantly reduced (intervention group 1) oral from 47 to 24 mg morphine 0-24 h, P , 0.003 Nefopam 20 mg 36 i.v. – Significantly reduced from 27.3 to 21.2 mg morphine 0-24 h, P 5 0.02 Dexmedetomidine 0.2 – Significantly reduced mg/kg per hour i.v. from 56.1 to 42.8 mg morphine 0-24 h, P , 0.05

Treatment effect on pain score at 6 h postoperatively

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Marino et al.55 Femoral nerve block with Ketorolac 30 mg i.m. ropivacaine (intervention 0 and 6 h group 1)

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Bilir et al.6

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NS Significant reduced at rest, P 5 0.04

* Length of stay. † Postoperative nausea and vomiting. i.v., intravenous; NS, nonsignificant p.0.05.

– Specht et al.79 Catheter infusion added Acetaminophen 1 g oral Significant reduced from 60 mm at 24-h rest to local infiltration 34 1 ibuprofen 400 mg 44 to 36 mg morphine 0analgesia with oral 34 24 h, P 5 0.05 ropivacaine 100 mg, ketorolac 15 mg, adrenaline 1 mg, at 10 and 22 h postoperatively

Treatment effect on pain score at 6 h postoperatively Highest level of postoperative pain in control group (VAS, 0-100 mm) (assay sensitivity) Reference

Intervention

Basic analgesic regimen

Treatment effect on analgesic requirement

Table 3 (continued)

Treatment effect on pain score at 24 h postoperatively

Length of hospital stay*

PONV†

NS

NS

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consumption and pain levels. Forty trials in the present review did not assess pain during mobilization, which is important because 1 of the goals of postoperative pain management is early and optimized mobilization.80 In 27 of the retrieved trials, the active intervention was studied as an adjunct to a basic analgesic regimen that often included multiple analgesics. Applying a basic analgesic regimen may reduce the maximal attainable morphine-sparing effect of an additional intervention. In accordance, pain scores or morphine consumption in control groups (assay sensitivity) were low in a number of trials (VAS below 30 mm14 or i.v. morphine consumption ,15 mg/24 h). In addition, these trials have an increased risk of reporting significant but irrelevant results.23 In consistence with previous reports,76 irregular and nonsystematic reporting of opioid- and intervention-specific adverse events in the majority of included trials was demonstrated. Only 11 trials assessed LOS, and none of these demonstrated significant differences between treatments. The quality of evidence ranged from low to very low throughout the analyses, according to GRADE. In summary, there is some evidence that a number of analgesic interventions, including NSAID or COX2 inhibitors, LIA, intrathecal opioids, and lumbar plexus block, have the capacity to reduce mean opioid requirements or mean pain intensity compared with controls after THA. The evidence is, however, flawed by considerable bias, heterogeneity in outcome parameters, and irregular and non-systematic reporting of adverse events, leading to very low to low quality of evidence, according to GRADE. There are several formal limitations to this review. Thus, we were unable to retrieve 20 possibly relevant articles. When authors of retrieved articles were contacted, they often failed to reply to our questions regarding bias, and these trials were consequently rated as “high risk” although the actual quality may have been higher than that stated in our bias assessment. In the original articles, different opioids were administered as rescue analgesics, and pain was registered on different pain scales. Conversion to morphine equivalents and VAS 0 to 100 mm may have caused inaccurate results. Opioid consumption was often reported as median and IQR, because of a skewed distribution.66 To perform meta-analyses, we had to convert such values to mean and SD, which is a potential and serious, but necessary shortcoming of our analyses. Finally, mean differences between intervention groups as an outcome have been criticized because pain relief often displays a bimodal distribution of either very good or poor.65 An alternative measure of analgesic effect is dichotomous reporting, where the reduction in pain score in individual patients must reach a (minimal) clinical relevant level before being considered effective. “No worse than mild pain” has been suggested as a simple universal outcome.67 We did not, however, have access to individual patient data. A contemporary systematic review with meta-analyses of RCTs may provide the best available evidence for effects of different analgesics in relation to a specific surgical procedure; furthermore, it may offer an impression of how well or “bad” the literature works in general. Traditional RCTs of specific interventions may demonstrate reductions in mean pain scores and opioid requirements from one level to another. These may not, however, be the most relevant clinical questions, and consequently, there are important limitations to this and other similar reviews of the current “procedure-specific” evidence. The final goal of effective pain treatment is to ensure the lowest pain intensity during rest and ambulation and the lowest need for supplemental opioids in a majority of patients. Moreover, to ensure minimal adverse effects and optimized rehabilitation.

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These challenges are most probably not solved by (reviews of) the current literature. Thus, a majority of the published RCTs may have used a well-defined surgical procedure as a model to investigate the efficacy of a particular, analgesic intervention, rather than investigating for the best possible procedure-specific, multimodal treatment option. Accordingly, we doubt that future traditional RCTs will ever tell us how to provide an effective multifaceted postoperative pain treatment. We suggest that future efforts to improve analgesia after THA should include large-scaled randomized trials with factorial designs, of combinations of different, well-documented nonopioid analgesics and local anesthetic techniques.17 Outcomes should include the number of patients with predefined “acceptable” pain levels at rest and during ambulation,67 opioid consumption, opioidrelated and intervention-specific adverse effects, and LOS adhering to specific goals within well-defined rehabilitation paradigms.16 In conclusion, this review of postoperative pain management after THA is, to the best of our knowledge, the first to include alllanguage trials, and to take both bias (including trial size), TSA and GRADE, into account. It has been documented that some analgesic interventions may have the capacity to reduce mean opioid requirements or mean pain intensity compared with controls. However, the quality of evidence is low or very low for the different regimens, and the available literature does not allow a designation of a “best proven intervention” for this surgical procedure.

Conflict of interest statement The authors have no conflicts of interest to declare.

Acknowledgements J. B. Dahl, O. Mathiesen, and A. P. H. Karlsen designed the study. A. P. H. Karlsen, O. Mathiesen, and J. B. Dahl screened trials for eligibility. A. P. H. Karlsen, A. Geisler, P. L. Petersen, and O. Mathiesen extracted data and assessed risk of bias. A. P. H. Karlsen and J. B. Dahl performed data analyses and A. P. H. Karlsen drafted the manuscript. J. B. Dahl was the primary reviser, and all authors contributed substantially to the revision. J. B. Dahl takes responsibility for the article as a whole. All authors met the International Committee of Medical Journal Editor’s specific requirements regarding the duties and responsibilities of authorship. No other than the above-mentioned authors contributed to the article.

Appendices. Supplemental Digital Content Appendices 1-12 are available online as Supplemental Digital Content at http://links.lww.com/PAIN/A2. Article history: Received 18 July 2014 Received in revised form 15 October 2014 Accepted 21 October 2014

References [1] Akin A, Esmaoglu A, Boyaci A. Preemptive effectiveness of piroxicam in patients undergoing total hip replacement. Turk Anesteziyoloji ve Reanimasyon 2002;30:161–65. [2] 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;78:187–92.

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[3] Anis S, Moaty NAE, Youssef A, Ramzy R, Hassan R. Lumbar plexus block as a method of postoperative analgesia after hip surgery. Egypt Soc Anesthesiologists 2011;27:127–33. [4] Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg 2003;97:534–40. [5] Benhamou D, Berti M, Brodner G, De Andres J, Draisci G, MorenoAzcoita M, Neugebauer EA, Schwenk W, Torres LM, Viel E. Postoperative Analgesic THerapy Observational Survey (PATHOS): a practice pattern study in 7 central/southern European countries. PAIN 2008;136:134–41. [6] Bilir A, Gulec S, Erkan A, Ozcelik A. Epidural magnesium reduces postoperative analgesic requirement. Br J Anaesth 2007;98:519–23. [7] 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;468:2152–9. [8] Camu F, Beecher T, Recker DP, Verburg KM. Valdecoxib, a COX-2specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty. Am J Ther 2002;9:43–51. [9] Carabine UA, Milligan KR, Mulholland D, Moore J. Extradural clonidine infusions for analgesia after total hip replacement. Br J Anaesth 1992;68: 338–43. [10] Chen DW, Hsieh PH, Huang KC, Hu CC, Chang YH, Lee MS. Continuous intra-articular infusion of bupivacaine for post-operative pain relief after total hip arthroplasty: a randomized, placebo-controlled, double-blind study. Eur J Pain 2010;14:529–34. [11] Chen DW, Hu CC, Chang YH, Lee MS, Chang CJ, Hsieh PH. Intraarticular Bupivacaine Reduces Postoperative Pain and Meperidine Use After Total Hip Arthroplasty: a Randomized, Double-blind Study. J Arthroplasty 2013;Available at: http://dx.doi.org/10.1016/j. arth.2013.12.021 [Epub ahead of print]. [12] Choice Pharma. Prospect. Available at: http://www.postoppain.org/ frameset.htm. Accessed on January 16, 2014. [13] Clarke H, Pereira S, Kennedy D, Andrion J, Mitsakakis N, Gollish J, Katz J, Kay J. Adding gabapentin to a multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplasty. Acta Anaesthesiol Scand 2009;53:1073–83. [14] Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres? PAIN 1997;72:95–7. [15] Coluzzi F, Savoia G, Paoletti F, Costantini A, Mattia C. Postoperative pain survey in Italy (POPSI): a snapshot of current national practices. Minerva Anestesiol 2009;75:622–31. [16] Dahl JB, Mathiesen O, Kehlet H. An expert opinion on postoperative pain management, with special reference to new developments. Expert Opin Pharmacother 2010;11:2459–70. [17] Dahl JB, Nielsen RV, Wetterslev J, Nikolajsen L, Hamunen K, Kontinen VK, Hansen MS, Kjer JJ, Mathiesen O, Scandinavian Postoperative Pain Alliance. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. Acta Anaesthesiol Scand 2014. doi: 10.1111/aas.12382. [Epub ahead of print]. [18] Dahl V, Raeder JC, Drøsdal S, Wathne O, Brynildsrud J. Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty. Acta Anaesthesiol Scand 1995;39:323–6. [19] Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta-epidemiological study. BMJ 2013;346:f2304. [20] 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;470:1958–65. [21] Dobrydnjov I, Axelsson K, Gupta A, Lundin A, Holmstrom B, Granath B. Improved analgesia with clonidine when added to local anesthetic during combined spinal-epidural anesthesia for hip arthroplasty: a double-blind, randomized and placebo-controlled study. Acta Anaesthesiol Scand 2005;49:538–45. [22] Du Manoir B, Aubrun F, Langlois M, Le Guern ME, Alquier C, Chauvin M, Fletcher D. Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery. Br J Anaesth 2003;91:836–41. [23] Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I, Jensen MP, Katz NP, Raja SN, Rappaport BA, Rowbotham MC, Backonja MM, Baron R, Bellamy N, Bhagwagar Z, Costello A, Cowan P, Fang WC, Hertz S, Jay GW, Junor R, Kerns RD, Kerwin R, Kopecky EA, Lissin D, Malamut R, Markman JD, McDermott MP, Munera C, Porter L, Rauschkolb C, Rice AS, Sampaio C, Skljarevski V, Sommerville K, Stacey BR, Steigerwald I, Tobias J, Trentacosti AM, Wasan AD, Wells GA, Williams J, Witter J, Ziegler D. Considerations for improving assay sensitivity in chronic pain clinical trials: impact recommendations. PAIN 2012;153:1148–58. [24] El Gendy HA, Elsharnouby NM. Ultrasound guided single injection caudal epidural anesthesia of isobaric bupivacaine with/without dexamethasone

Copyright Ó 2014 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.

January 2015

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44] [45] [46]

·

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·

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for geriatric patients undergoing total hip replacement surgery. Egypt J Anaesth 2014;30:293–8. Erol TM, Ozdogan L, Ornek D, Taspinar V, Kalayci D, Barcin S, Sahin F, Erk G, Dikmen B. Effect of ketamine on the quality of anesthesia and postoperative analgesia in epidural anesthesia. J Exp Clin Med 2014;6: 83–9. Fernandez-Liesa ´ JI, Mednieta JM, Vaquerizo A, Azaceta-Reinares G, Calderon R. Effect of intrathecal methadone on postoperative analgesia after total hip arthoplasty. Acute Pain 2000;3:206–10. Fletcher D, Fermanian C, Mardaye A, Aegerter P, Pain, Regional Anesthesia Committee of the French A, Intensive Care S. A patientbased national survey on postoperative pain management in France reveals significant achievements and persistent challenges. PAIN 2008; 137:441–51. Fletcher D, Zetlaoui P, Monin S, Bombart M, Samii K. Influence of timing on the analgesic effect of intravenous ketorolac after orthopedic surgery. PAIN 1995;61:291–7. Fogarty DJ, Carabine UA, Milligan KR. Comparison of the analgesic effects of intrathecal clonidine and intrathecal morphine after spinal anaesthesia in patients undergoing total hip replacement. Br J Anaesth 1993;71:661–4. Fournier R, Van Gessel E, Gaggero G, Boccovi S, Forster A, Gamulin Z. Postoperative analgesia with “3-in-1” femoral nerve block after prosthetic hip surgery. Can J Anaesth 1998;45:34–8. Garg R, Banwait S, Pawar M, Sharma S, Sood R. Evaluation of single epidural bolus dose of magnesium as an adjuvant to epidural fentanyl for postoperative analgesia: a prospective, randomized, double-blind study. Saudi J Anaesth 2012;6:273–8. Available from: http://onlinelibrary.wiley. com/o/cochrane/clcentral/articles/881/CN-00901881/frame.html. http://www.saudija.org/article.asp?issn51658‐354X;year52012; volume56;issue53;spage5273;epage5278;aulast5Banwait. Grace D, Milligan KR, Morrow BJ, Fee JPH. Co-administration of pethidine and clonidine: a spinal anaesthetic technique for total hip replacement. Br J Anaesth 1994;73:628–33. Grace D, Bunting H, Milligan KR, Fee JP. Postoperative analgesia after co-administration of clonidine and morphine by the intrathecal route in patients undergoing hip replacement. Anesth Analg 1995;80:86–91. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ, Group GW. What is “quality of evidence” and why is it important to clinicians? BMJ 2008;336:995–8. Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011], The Cochrane Collaboration, 2009. Available at: http://www.cochrane-handbook.org. Accessed on March 14, 2014. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods G, Cochrane Statistical Methods G. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005;5:13. Hwang JY, Na HS, Jeon YT, Ro YJ, Kim CS, Do SH. I.V. infusion of magnesium sulfate during spinal anaesthesia improves postoperative analgesia. Br J Anaesth 2010;104:89–93. Informatics and Knowledge Management Department. Denmark: The Cochrane Collaboration;2012 Available at: http://tech.cochrane.org/ revman. Accessed on January 29, 2014. Iohom G, Walsh M, Higgins G, Shorten G. Effect of perioperative administration of dexketoprofen on opioid requirements and inflammatory response following elective hip arthroplasty. Br J Anaesth 2002;88:520–6. Joshi GP, Schug SA, Kehlet H. Procedure-specific pain management and outcome strategies. Best Pract Res Clin Anaesthesiol 2014;28: 191–201. Kampe S, Weigand C, Kaufmann J, Klimek M, Konig DP, Lynch J. Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement. Anesth Analg 1999;89:395–8. Kardash KJ, Sarrazin F, Tessler MJ, Velly AM. Single‐dose dexamethasone reduces dynamic pain after total hip arthroplasty. Anesth Analg 2008;106:1253–7. Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postoperative recovery. Lancet 2003;362:1921–8. Kehlet H, Wilmore DW. Evidence-based surgical care and the evolution of fast-track surgery. Ann Surg 2008;248:189–98. Kelly AM. Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Acad Emerg Med 1998;5:1086–90.

www.painjournalonline.com

29

[47] Klasen J, Haas M, Graf S, Harbach H, Quinzio L, Jurgensen I, Hempelmann G. Impact on postoperative pain of long-lasting preemptive epidural analgesia before total hip replacement: a prospective, randomised, double-blind study. Anaesthesia 2005;60:118–23. [48] Kostamovaara PA, Laurila JJ, Alahuhta S, Salomaki TE. Ropivacaine 1 mg x ml(-1) does not decrease the need for epidural fentanyl after hip replacement surgery. Acta Anaesthesiol Scand 2001;45:489–94. [49] Laitinen J, Nuutinen L. Intravenous diclofenac coupled with PCA fentanyl for pain relief after total hip replacement. Anesthesiology 1992;76:194–8. [50] 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;12:387–93. [51] Lunn TH, Andersen LO, Kristensen BB, Husted H, Gaarn-Larsen L, Bandholm T, Ladelund S, Kehlet H. Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial. Br J Anaesth 2013;110:66–73. [52] Lunn TH, Husted H, Solgaard S, Kristensen BB, Otte KS, Kjersgaard AG, Gaarn-Larsen L, Kehlet H. Intraoperative local infiltration analgesia for early analgesia after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain Med 2011;36:424–9. [53] Malan TP Jr, Marsh G, Hakki SI, Grossman E, Traylor L, Hubbard RC. Parecoxib sodium, a parenteral cyclooxygenase 2 selective inhibitor, improves morphine analgesia and is opioid-sparing following total hip arthroplasty. Anesthesiology 2003;98:950–6. [54] Manoir BD, Bourget P, Langlois M, Szekely B, Fischler M, Chauvin M, Paci A, Fletcher D. Evaluation of the pharmacokinetic profile and analgesic efficacy of oral morphine after total hip arthroplasty. Eur J Anaesthesiol 2006;23:748–54. [55] Marino J, Russo J, Kenny M, Herenstein R, Livote E, Chelly JE. Continuous lumbar plexus block for postoperative pain control after total hip arthroplasty. A randomized controlled trial. J Bone Joint Surg Am 2009;91:29–37. [56] Martin F, Cherif K, Gentili ME, Enel D, Abe E, Alvarez JC, Mazoit JX, Chauvin M, Bouhassira D, Fletcher D. Lack of impact of intravenous lidocaine on analgesia, functional recovery, and nociceptive pain threshold after total hip arthroplasty. Anesthesiology 2008;109:118–23. [57] Martinez V, Belbachir A, Jaber A, Cherif K, Jamal A, Ozier Y, Sessler DI, Chauvin M, Fletcher D. The influence of timing of administration on the analgesic efficacy of parecoxib in orthopedic surgery. Anesth Analg 2007; 104:1521–7. [58] Martinez V, Cymerman A, Ben Ammar S, Fiaud JF, Rapon C, Poindessous F, Judet T, Chauvin M, Bouhassira D, Sessler D, Mazoit X, Fletcher D. The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double-blind, controlled study. Anaesthesia 2014;69:46–52. [59] Mathiesen O, Jacobsen LS, Holm HE, Randall S, Adamiec-Malmstroem L, Graungaard BK, Holst PE, Hilsted KL, Dahl JB. Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty. Br J Anaesth 2008;101:535–41. [60] Mathiesen O, Thomsen BA, Kitter B, Dahl JB, Kehlet H. Need for improved treatment of postoperative pain. Dan Med J 2012;59:A4401. [61] Mendieta Sanchez JM, Fernandez-Liesa JI, Marco G, Panadero A, Sanchez-Ledesma MJ, Macias A. Efficacy of 0.1 mg of subarachnoid morphine combined with bupivacaine on postoperative analgesia in total hip arthroplasty [Article in Spanish]. Rev Esp Anestesiol Reanim 1999;46:433–7. [62] Milligan KR, Convery PN, Weir P, Quinn P, Connolly D. The efficacy and safety of epidural infusions of levobupivacaine with and without clonidine for postoperative pain relief in patients undergoing total hip replacement. Anesth Analg 2000;91:393–7. [63] Milligan KR, Fogarty DJ. The characteristics of analgesic requirements following subarachnoid diamorphine in patients undergoing total hip replacement. Reg Anesth 1993;18:114–7. [64] Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006–12. [65] Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. BMJ 2013;346:f2690. [66] Moore RA, Mhuircheartaigh RJ, Derry S, McQuay HJ. Mean analgesic consumption is inappropriate for testing analgesic efficacy in postoperative pain: analysis and alternative suggestion. Eur J Anaesthesiol 2011;28:427–32. [67] Moore RA, Straube S, Aldington D. Pain measures and cut-offs-no worse than mild pain’ as a simple, universal outcome. Anaesthesia 2013;68: 400–12. [68] Murphy PM, Stack D, Kinirons B, Laffey JG. Optimizing the dose of intrathecal morphine in older patients undergoing hip arthroplasty. Anesth Analg 2003;97:1709–15.

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[69] Murphy TP, Byrne DP, Curtin P, Baker JF, Mulhall KJ. Can a periarticular levobupivacaine injection reduce postoperative opiate consumption during primary hip arthroplasty? Clin Orthop Relat Res 2012;470:1151–7. [70] Pandazi A, Kanellopoulos I, Kalimeris K, Batistaki C, Nikolakopoulos N, Matsota P, Babis GC, Kostopanagiotou G. Periarticular infiltration for pain relief after total hip arthroplasty: a comparison with epidural and PCA analgesia. Arch Orthop Trauma Surg 2013;133:1607–12. [71] Peduto VA, Ballabio M, Stefanini S. Efficacy of propacetamol in the treatment of postoperative pain. Morphine-sparing effect in orthopedic surgery. Italian Collaborative Group on Propacetamol. Acta Anaesthesiol Scand 1998;42:293–8. [72] Remerand F, Le Tendre C, Baud A, Couvret C, Pourrat X, Favard L, Laffon M, Fusciardi J. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Anesth Analg 2009;109:1963–71. [73] Samir E, Badawy S, Hassan A. Intrathecal vs intravenous magnesium as an adjuvant to bupivacaine spinal anesthesia for total hip arthroplasty. Egypt J Anaesth 2013;29:395–400. [74] Segstro R, Morley-Forster PK, Lu G. Indomethacin as a postoperative analgesic for total hip arthroplasty. Can J Anaesth 1991;38:578–81. [75] Serpell MG, Thomson MF. Comparison of piroxicam with placebo in the management of pain after total hip replacement. Br J Anaesth 1989;63: 354–6. [76] Smith SM, Wang AT, Katz NP, McDermott MP, Burke LB, Coplan P, Gilron I, Hertz SH, Lin AH, Rappaport BA, Rowbotham MC, Sampaio C, Sweeney M, Turk DC, Dworkin RH. Adverse event assessment, analysis, and reporting in recent published analgesic clinical trials: action systematic review and recommendations. PAIN 2013;154:997–1008. [77] Solovyova O, Lewis CG, Abrams JH, Grady-Benson J, Joyce ME, Schutzer SF, Arumugam S, Caminiti S, Sinha SK. Local infiltration analgesia followed by continuous infusion of local anesthetic solution for total hip arthroplasty: a prospective, randomized, double-blind, placebocontrolled study. J Bone Joint Surg Am 2013;95:1935–41. [78] Song F. Exploring heterogeneity in meta-analysis: is the L’Abbe plot useful? J Clin Epidemiol 1999;52:725–30.

PAIN®

[79] Specht K, Leonhardt JS, Revald P, Mandoe H, Andresen EB, Brodersen J, Kreiner S, Kjaersgaard-Andersen P. No evidence of a clinically important effect of adding local infusion analgesia administrated through a catheter in pain treatment after total hip arthroplasty. Acta Orthop 2011;82:315–20. [80] Srikandarajah S, Gilron I. Systematic review of movement-evoked pain versus pain at rest in postsurgical clinical trials and meta-analyses: a fundamental distinction requiring standardized measurement. PAIN 2011;152:1734–9. [81] Stevens M, Harrison G, McGrail M. A modified fascia iliaca compartment block has significant morphine-sparing effect after total hip arthroplasty. Anaesth Intensive Care 2007;35:949–52. [82] Stevens RD, Van Gessel E, Flory N, Fournier R, Gamulin Z. Lumbar plexus block reduces pain and blood loss associated with total hip arthroplasty. Anesthesiology 2000;93:115–21. [83] Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C. User Manual for Trial Sequential Analysis (TSA). Copenhagen, Denmark: Rigshospitalet, Copenhagen Trial Unit, Center for Clinical Intervention Research, Department 3344. [84] Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med 1996;27:485–9. [85] Utebey G, Akkaya T, Alptekin A, Sayin M, Gumus H, Ates Y. The effects of lumbar plexus block and epidural block on total blood loss and postoperative analgesia in total hip arthroplasty [in Turkish]. Agri 2009; 21:62–8. [86] Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol 2008;61:64–75. [87] Wu ZL, Zhou ZF, Xu LX, She SZ. Effect of dexmedetomidine on patientcontrolled intravenous analgesia with fentanyl in elderly patients after total hip replacement [in Chinese]. Nan Fang Yi Ke Da Xue Xue Bao 2011;31:701–4. [88] Zoric L, Cuvillon P, Alonso S, Demattei C, Vialles N, Asencio G, Ripart J, Nouvellon E. 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;112:722–8.

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Postoperative pain treatment after total hip arthroplasty: a systematic review.

Treatment of postoperative pain should rely on results from randomized controlled trials and meta-analyses of high scientific quality. The efficacy of...
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