Evidence review for anaesthesia for hip replacement

National Guideline Centre (UK)

Evidence review for anaesthesia for hip replacement

Joint replacement (primary): hip, knee and shoulder

Evidence review D

NICE Guideline, No. 157

Authors

National Guideline Centre (UK).

London: National Institute for Health and Care Excellence (NICE); 2020 Jun.

ISBN-13: 978-1-4731-3722-6

1. Anaesthesia for elective hip joint replacement

1.1. Review question: In adults having primary elective hip joint replacement, what is the clinical and cost effectiveness of intraoperative anaesthetic approaches: regional anaesthesia or general anaesthesia, with or without nerve blocks and local infiltration analgesia, compared with each other or in combination?

1.2. Introduction

Total hip replacement surgery is painful. The anaesthetist and person undergoing surgery can choose from a number of interventions which aim to minimise this.

Firstly there is a choice of underlying anaesthesia and the options are general anaesthesia, regional anaesthesia, or a combination of both. General anaesthesia is where the patient is put into a deep sleep. Regional anaesthesia is where only part of the body is anaesthetised, using local anaesthetic to ‘turn off’ the nerves temporarily. During this time, the patient is typically aware of some pushing or pulling, but no pain.

Once it has been decided whether to use general, regional anaesthesia or both, then the technique or combination of techniques, needed to prevent pain after the operation should be considered. Preventing early pain is important in itself and, it is also recognised that reducing pain in the first few hours after surgery may help reduce pain over a longer period.

There are 2 supplementary anaesthetic options that can be utilised. Firstly, local anaesthetic infiltration where a large volume of anaesthetic is injected into the tissues around the operation site. This technique typically lasts for 8 to 10 hours. A second approach is to target an injection of anaesthetic to the nerves that supply the hip joint, often using an ultrasound machine to identify the nerve. Local anaesthetic infiltration and nerve blocks can be performed separately, or together.

This review seeks to determine the most clinically effective and cost-effective approach to both types of anaesthetic, and the type of supplementary anaesthetic options for total hip replacement.

1.3. PICO table

For full details see the review protocol in Appendix A:

Table 1

PICO characteristics of review question.

1.4. Clinical evidence

1.4.1. Included studies

A search was conducted for trials comparing the effectiveness of intraoperative anaesthesia and analgesia routines utilised for hip joint replacement surgery.

Twenty four RCTs and five observational studies were included in the review;¹⁸^, ⁴⁰^, ⁵⁶^, ⁶¹^, ⁶²^, ⁶⁴^, ⁶⁶^, ⁶⁹^, ⁸⁹^–⁹¹^, ⁹⁶^, ⁹⁷^, ¹⁰¹^, ¹⁰²^, ¹⁰⁵^, ¹³²^, ¹³³^, ¹⁴⁰^, ¹⁴³^, ¹⁵¹^, ¹⁶²^, ¹⁶⁵^, ¹⁷¹^, ²²²^, ²²⁴^, ²³⁰^, ²³⁶^, ²³⁸ these are summarised in Table 2 below. The RCTs were too small to accurately assess an outcome as rare as mortality and this was thought to be a key difference between regional anaesthesia and general anaesthesia. Therefore observational studies were included for the mortality within 90 days outcome for the regional anaesthesia versus general anaesthesia comparison. Evidence from these studies is summarised in the clinical evidence summary below (Table 3). See also the study selection flow chart in Appendix C: study evidence tables in Appendix D: forest plots in Appendix E: and GRADE tables in Appendix H:

1.4.2. Excluded studies

See the excluded studies list in Appendix I:

1.4.3. Summary of clinical studies included in the evidence review

Table 2

Summary of studies included in the evidence review.

See Appendix D: for full evidence tables.

1.4.4. Quality assessment of clinical studies included in the evidence review

Table 3

RCT evidence summary: regional anaesthesia with nerve block versus regional anaesthesia.

Table 4

RCT evidence summary: Regional anaesthesia with LIA versus regional anaesthesia with nerve block.

Table 5

RCT evidence summary: Regional anaesthesia with LIA versus regional anaesthesia.

Table 6

RCT evidence summary: regional anaesthesia versus general anaesthesia.

Table 7

Observational studies evidence summary: regional anaesthesia versus general anaesthesia.

Table 8

RCT evidence summary: General anaesthesia with LIA versus general anaesthesia with nerve block.

Table 9

RCT evidence summary: General anaesthesia with LIA versus general anaesthesia.

Table 10

RCT evidence summary: General anaesthesia with nerve block versus general anaesthesia.

See Appendix F: for full GRADE tables.

1.5. Economic evidence

1.5.1. Included studies

Two health economic studies were identified with the relevant comparison and have been included in this review.⁸⁸^, ¹⁴⁷. The studies are summarised in the health economic evidence profile below (Table 11) and the health economic evidence table in Appendix H: One original threshold analysis was conducted which can be found in Appendix I:

1.5.2. Excluded studies

No health economic studies that were relevant to this question were excluded due to assessment of limited applicability or methodological limitations.

See also the health economic study selection flow chart in Appendix G:

1.5.3. Summary of studies included in the economic evidence review

Table 11

Health economic evidence profile: LAI in addition to a standard anaesthetic regimen versus standard anaesthetic regimen only.

Table 12

Health economic evidence profile: Spinal anaesthesia versus general anaesthesia.

1.5.4. Health economic modelling

A threshold analysis was conducted on the addition of nerve blocks to an anaesthetic regimen. The method and results of the analysis can be found in Appendix I:Nerve block threshold analysis. The analysis uses estimates of incremental cost to find what QALY or utility gain is required at a given threshold of cost effectiveness. The threshold selected for this analysis was £20,000 in line with the NICE reference case. A range of incremental costs driven by the time required to administer the nerve block (30 minutes, 10 minutes and 5 minutes) and if the cost of theatre time was incorporated (yes or no) were included in the analysis. The rationale for having theatre time included as a cost variable is that the committee suggested that if 2 anaesthetists are available a nerve block can be administered in the anaesthesia room, not incurring additional theatre time costs. Therefore, for scenarios where theatre time was not included, 2 consultant anaesthetists were costed in. Whereas when theatre time was included, only one consultant anaesthetist was costed in. The results found that a nerve block is unlikely to be cost effective the longer it takes to administer, the shorter the effect duration, and if theatre time cost is included. However there are circumstances, such as when administration time is short, effect duration is long and theatre time is not included, when a nerve block could be cost effective. The different combinations of these factors are present across the NHS, so nerve blocks may be a viable cost-effective anaesthetic intervention for some hospitals but not for others.

1.5.5. Unit costs

The unit costs presented in Table 13 are for general and regional anaesthesia in a hip fracture population. Hip fracture is outside of the scope for this guideline. However, the committee felt the costs would be informative for a primary elective hip arthroplasty population. Table 14 shows the UK cost for the addition of a nerve block to any anaesthetic regimen when varying the time it takes to administer a nerve block and if the cost of theatre time is included or not.

$Table 13. Mean costs of anaesthesia for hip fracture in a UK hospital in 2010.$

Table 13

Mean costs of anaesthesia for hip fracture in a UK hospital in 2010.

Table 14

UK 2018 cost for the addition of a nerve block to an anaesthetic regimen for primary elective joint replacement when varying administration time and the inclusion of theatre time cost.

1.6. Evidence statements

1.6.1. Clinical evidence statements

24 RCTs covering 8 comparisons were included in the evidence review with relevant outcomes found for 7 of the comparisons. Data from 2 observational studies was utilised for the mortality within 90 days outcome for the regional anaesthesia versus general anaesthesia comparison.

Regional anaesthesia with nerve block versus regional anaesthesia was compared in 2 RCTs (n=145) with the majority of outcomes graded very low quality. A benefit was found for regional anaesthesia with nerve block in postoperative pain. No difference between treatment groups was found for 2 postoperative use of analgesia outcomes, nausea, or mobilisation. No outcomes favoured regional anaesthesia alone.

Regional anaesthesia with LIA versus regional anaesthesia with nerve block was compared in 1 RCT (n=56). All outcomes favoured regional anaesthesia with LIA. These were postoperative use of analgesia (moderate quality) and nausea (low quality).

Regional anaesthesia with LIA versus regional anaesthesia was compared in 7 RCTs (n=900) with quality ranging from high to very low. A benefit was found for regional anaesthesia with LIA in 2 postoperative use of analgesia outcomes, and 1 mobilisation outcome. All other outcomes indicated no difference between treatment groups, these were 2 postoperative pain outcomes, thromboembolic complications, length of stay, nausea, and 1 mobilisation outcome.

Regional anaesthesia versus general anaesthesia was compared in 5 RCTs (n=308) and 5 observational studies (n=314,352). The RCT evidence indicated a benefit of regional anaesthesia in postoperative use of analgesia (very low quality) and conversely a benefit was found for general anaesthesia in terms of length of stay (very low quality). No difference between interventions for mobilisation (moderate quality). 2 observational studies did not find a clinically important difference between treatment groups in terms of mortality (n=283,176, very low quality).

General anaesthesia with LIA versus general anaesthesia with nerve block was compared in 1 RCT (n=100) with outcomes graded as moderate or high quality. A benefit was found for general anaesthesia with LIA in terms of quality of life. No difference between treatment groups was found for postoperative use of analgesia and length of stay. No outcomes favoured general anaesthesia with nerve block.

General anaesthesia with LIA versus general anaesthesia was compared in 4 RCTs (n=342). All 8 outcomes indicated no difference between interventions. These were postoperative pain (very low quality), postoperative neurocognitive decline (very low quality), postoperative use of analgesia (moderate quality), length of stay (moderate quality), nausea (very low quality), and 2 mobilisation outcomes (moderate or very low quality).

General anaesthesia with nerve block versus general anaesthesia was compared in 3 RCTs (n=136). 1 RCT contained 2 relevant outcomes and both found a benefit for general anaesthesia with nerve block. These 2 outcomes were postoperative pain (low quality) and postoperative use of analgesia (very low quality).

1.6.2. Health economic evidence statements

One cost utility analysis found that using local anaesthetic wound infiltration in addition to a regional and/or general anaesthesia was dominant (less costly and more effective) compared to regional and/or general anaesthesia alone in people having an elective total hip replacement. This analysis was assessed as directly applicable with minor limitations.

One cost comparison found that using spinal anaesthesia was cost saving compared to general anaesthesia in people having an elective total hip replacement. This analysis was assessed as partially applicable with potentially serious limitations.

One original threshold analysis for the addition of a nerve block to any anaesthetic regimen found that nerve blocks are unlikely to be cost effective if theatre time is included in the incremental cost or if administration time is longer. However, it is possible the addition of a nerve block is cost effective if administration time is short, the cost of theatre time is not included and if the duration of effect used in the analysis is longer. The cost of theatre time can be excluded when there are two anaesthetists present so that the nerve block can be administered in the anaesthesia room, therefore not taking up extra theatre time.

1.7. The committee’s discussion of the evidence

1.7.1. Interpreting the evidence

1.7.1.1. The outcomes that matter most

The critical outcomes are mortality, quality of life, postoperative pain, postoperative neurocognitive decline, thromboembolic complications, and hospital readmission. The follow-up time point for mortality, the most critical outcome, was specified to be within 90 days because the committee were concerned that there are confounding factors that will not be adequately resolved over longer time periods. There are many factors outside of anaesthetic utilised during joint replacement surgery that contribute towards mortality and these expand as a person moves further on in their life. The committee were aware the trials would not be of an adequate size to balance these factors between treatment groups. Postoperative pain is of critical importance as it represents a central aspect of a person’s initial experience of joint replacement surgery. In addition the committee agreed that there is an argument that acute pain is a predictor of chronic pain and therefore reducing postoperative pain reduces future chronic pain. Postoperative neurocognitive decline is a key decision making outcome for the people undergoing joint replacement surgery. The committee anaesthetist said that neurocognitive decline was a major concern highlighted by people when these decision making conversations occur.

Important outcomes are postoperative use of analgesia, length of stay, nausea, and mobilisation within 24 hours after surgery. Postoperative use of analgesia is an indirect indicator of postoperative pain and as such is a useful measure for anaesthetic approach. Reduced length of stay is a very important outcome to those undergoing surgery and has economic implications. The anaesthetic approach may impact when a person can mobilise themselves. A person’s ability mobilise themselves shortly after surgery represents the early experience of a hip joint replacement and also whether they can be discharged from hospital.

1.7.1.2. The quality of the evidence

The overall outcome quality ranged from high to very low. More outcomes were assessed as low or very low quality than moderate or high quality.

The evidence was often downgraded for risk of bias because studies that did not state an adequate method of randomisation or gave an adequate description of allocation concealment. A further reason for risk of bias was due to the difficulty of blinding in surgical treatment meant that subjective outcomes were occasionally assessed by people who knew the anaesthetic treatment used.

Two thirds of the outcomes were downgraded in quality due to imprecision. Only 1 outcome was downgraded for inconsistency. This was not explained by subgroup analysis and a random effects model was utilised.

1.7.1.3. Benefits and harms

24 randomised controlled trials were included in the evidence review. These trials encompassed 8 comparisons though relevant evidence was found for 7 of the comparisons. The study investigating the 8^th comparison did not contain relevant outcomes. A network meta-analysis was considered for this analysis but there were no suitable outcomes reported across the comparisons to facilitate this approach. Many studies were excluded as it was unclear if the hip arthroplasty being undertaken was primary arthroplasty. The committee agreed that revision surgery is different enough from primary arthroplasty that studies where primary arthroplasty was not specified should be excluded. In addition it was important that the postoperative analgesia followed the same protocol for both treatment groups in each study to prevent confounding.

Comparisons including only regional anaesthesia

Regional anaesthesia alone was compared to regional anaesthesia with LIA and regional anaesthesia with nerve block. Regional anaesthesia alone often appeared to be of similar effectiveness to regional anaesthesia augmented with LIA or nerve blocks. 9 outcomes indicated no difference between the two anaesthetic regimes. However 4 outcomes did favour augmented regional over regional alone though conversely 1 outcome indicated a benefit of regional alone over augmented regional. When regional with LIA was compared to regional with nerve block, the only 2 outcomes indicated a benefit of the former. However these outcomes came from 1 study with 56 participants.

Comparisons including only general anaesthesia

General anaesthesia alone was compared to general anaesthesia with LIA and all 9 outcomes indicated no difference between the approaches. General anaesthesia alone was compared to general anaesthesia with nerve block in 2 outcomes taken from 1 study with 80 participants, and both indicated a benefit of general with nerve block. General with LIA was compared to general with nerve block in 3 outcomes taken from 1 study with 100 participants. These indicated a benefit for general with LIA for quality life and no difference for the other 2 outcomes.

Comparisons including both regional and general anaesthesia

2 studies with extractable outcomes compared general to regional anaesthesia. The studies found a benefit for regional in postoperative use of analgesia, a benefit for general in mobilization within 24 hours, and no difference in length of stay. The RCT clinical evidence data did not provide strong enough evidence to differentiate between regional or general anaesthesia.

It was then decided to look for mortality outcomes in non-randomised studies comparing regional anaesthesia to general anaesthesia. The committee were interested in this particular comparison because it is thought that general anaesthesia leads to greater mortality than regional anaesthesia and this might be a method by which they could be separated. This data was sought because the RCTs were of insufficient size to accurately assess an outcome as rare as mortality. NJR data was utilised in one study where it was adjusted for confounding factors. 5 relevant non-randomised studies were found but only two reported mortality. Both studies consistently reported a small benefit for regional anaesthesia over general anaesthesia though one study did have very wide confidence intervals. However despite the studies showing a small benefit of regional anaesthesia, the rarity of mortality in this surgery did not indicate a clinically important effect and the committee did not decide to recommend regional anaesthesia over general anaesthesia.

When discussing the overall arc of the evidence the committee discussed when regional anaesthesia alone was compared to regional anaesthesia augmented with LIA or nerve blocks and when general anaesthesia alone was compared to general anaesthesia augmented with LIA or nerve blocks. There was commonly outcomes that indicated no difference between treatments but outside of that there was a benefit of the augmented anaesthesia. The solo interventions rarely show a clinically important benefit.

The committee agreed that overall there was no evidence found for postoperative neurocognitive decline for any of the approaches and this is an important benefit for the person undergoing surgery. The evidence found did not indicate any differences in length of stay and in nearly every case in terms of mobilisation.

The committee agreed that the evidence did not indicate a difference between general or regional anaesthesia. In addition there did appear to be some benefit of augmenting these approaches with LIA or nerve blocks. The guideline anaesthetist indicated that it makes sense to utilise additional techniques on top of regional or general because multimodal anaesthesia approaches the complex problem from multiple angles and provides more ways of reducing postoperative pain.

The committee made recommendations for offering regional or general anaesthesia in combination with LIA, or nerve blocks as an alternative to LIA, based on their experience and the evidence. They agreed the combination reduces postoperative pain and the evidence showed that both nerve blocks and LIA are beneficial when used with general or regional anaesthesia.

The committee were keen to highlight the personalised care aspect that should stay within the anaesthetist’s sphere of control. The knowledge and experience of the anaesthetist should be utilised when considering patient characteristics in accordance with best practice. Thus all options can be considered by the anaesthetist given individual patient circumstances/characteristics.

A patient member of committee indicated that people get confused around anaesthesia choices and full explanations of the risks and benefits of each approach are important person’s wellbeing both before and after surgery. These explanations must be pitched correctly for a benefit to be seen.

1.7.2. Cost effectiveness and resource use

Two studies were presented; the first found that the addition of LIA to regional or general was dominant (less costly and more effective) compared to regional or general alone. The second found that regional (spinal) anaesthesia was cost saving over general anaesthesia. There was a lack of economic evidence presented regarding the use of nerve blocks.

Any difference in mortality and morbidity was not fully accounted for in the initial clinical review as the time horizon for inclusion was too short. The observational evidence subsequently presented suggested that there was not a significant difference in mortality between regional and general anaesthesia.

Unit costs of regional and general anaesthesia for a hip fracture population were presented. These showed that regional anaesthesia was cost saving. There was suggestion that these were representative of costs for a primary total hip replacement as well. However, there were also differing views put forward on if there was a true difference in costs. There was consensus that time is gained at the end of a total hip replacement using spinal anaesthesia as the patient leaves the theatre straight away. By contrast, for general anaesthesia the patient leaving the theatre must be timed with certain factors such as the different dressings applied. The lay perspective also discussed about personal experience of longer recovery times whilst under general anaesthetic. The cost of the extra recovery time represents an additional cost, however general may still be more appropriate for certain people.

The committee discussed that there is a difference in analgesic time between LIA and nerve blocks. There was consensus that using LIA is unlikely to represent significant additional costs in terms of time or personnel as it is often administered in redundant theatre time.

A nerve block may take up to 5 minutes of additional theatre time for those who are familiar with the procedure. There may be further additional time required initially for those who are not familiar with using nerve blocks. Some members of the committee shared experience of nerve block administration time being as high as 45 minutes, although this would be a rarity. The unit cost of £14.22 per minute for theatre time (including implant cost, personnel, overheads, consumables and facilities) presented from the economic evidence was thought to be very low; a more realistic unit cost of theatre time would be around £20.50 as included in CG124¹⁶⁸.

Given the lack of evidence and uncertainty surrounding the augmentation of an anaesthetic regimen with nerve blocks, a threshold analysis was conducted. The analysis showed what gain in quality adjusted life years (QALY) and health related quality of life (HRQoL) is necessary for an anaesthetic regimen augmented with nerve block to be cost effective at a threshold of £20,000 per QALY. Three factors highlighted by the committee as variable across the NHS were explored in the analysis. These factors were the time it takes to administer the nerve block (5 minutes, 10 minutes and 30 minutes); the length of time that the nerve block has an effect for (24 hours, 3 days, 10 days and 30 days); and if the cost of theatre time should be included or not. The rationale for having theatre time included as a cost variable was that the committee suggested that if 2 anaesthetists are available a nerve block can be administered in the anaesthesia room, not incurring additional theatre time costs. Therefore, for scenarios where theatre time was not included, 2 consultant anaesthetists were costed in. Whereas when theatre time was included, only one consultant anaesthetist was costed in.

Outlined below is the QALY gain needed based on the time taken to administer the nerve block and whether or not theatre time was included:

Administration time 30 minutes with theatre time: 0.034
Administration time 10 minutes with theatre time: 0.012
Administration time 5 minutes with theatre time: 0.006
Administration time 30 minutes with no theatre time: 0.006
Administration time 10 minutes with no theatre time: 0.002
Administration time 5 minutes with no theatre time: 0.002

The gain in HRQoL necessary at range of time horizons for all scenarios listed in the bullet points above was calculated (24 hours, 3 days, 10 days and 30 days). The results indicated that for a number of scenarios; particularly when the time to administer was 30 minutes, the intervention effect was 24 hours and when the cost of theatre time was included; the likelihood of nerve blocks being cost effective was impossible given that the gain in HRQoL needed was greater than 1 (given the assumed scale ranges from 0 to 1). When the assumptions were softened to their respective middle values, the gain in HRQoL was often not impossible (the gain needed was less than 1) but improbable. Finally, when time to administer was 5 minutes, the intervention effect was 30 days and when theatre time was excluded, the gain in HRQoL and therefore cost-effectiveness was more realistic.

The committee acknowledged that the time required for administration and the inclusion of the cost of theatre time was dependent on the experience of the anaesthetist and if two anaesthetists are available, respectively. All combinations of personnel numbers and time taken for administration can be found on the NHS at present. The third factor, the length of time that nerve blocks have an effect could be argued to be anything between a matter of hours to a lifetime. The analgesic effect of a nerve block is variable but may be 8 hours on average for hip replacements. However, a 24 hour time horizon may be the most appropriate when considering acute post-operative outcomes (for example, pain, post-operative nausea and vomiting). A longer effect duration of 10 days to 30 days may be most appropriate to account for the possible effect of anaesthetic choice on adverse clinical outcomes (for example post-operative morbidity and mortality). Lastly, an even longer time horizon would be needed to account for long term outcomes (such as chronic pain, opioid dependence and range of motion).

The committee agreed that there is clinical benefit to the addition of nerve blocks, although they are only likely to be cost effective when administered by an experienced anaesthetist, theatre time is not included (so two anaesthetists are present) and the effect duration is longer. The circumstances when nerve blocks are cost effective may be found in some hospitals but not in others.

Due to evidence suggesting that the addition of LIA to regional or general anaesthesia is clinically and cost effective, a recommendation was made offering this combination of anaesthesia. As the committee thought there may be a clinical benefit when adding a nerve block to regional or general anaesthesia, but concerns remained regarding the cost effectiveness, a weaker recommendation was made to consider the use of a nerve block over LIA. As no clinical evidence was found for the addition of a nerve block to LIA and regional or general anaesthesia, no recommendation was made for this combination. There were roughly 75,000 total hip replacements in 2017, all of which require some form of anaesthetic. All orthopaedic units currently offer a choice of general or regional anaesthesia. Most will augment this with either LIA or a nerve block. Although the cost of nerve blocks varies, it is not expected that services currently offering LIA will change to nerve blocks. This recommendation is unlikely to lead to significant change from current practice.

1.7.3. Other factors the committee took into account

A committee member spoke about the NHS history vis-a-vis regional anaesthesia. In 1946 in the Chesterfield Royal Infirmary spinal anaesthetic was used in 3 people who were paralysed as a result. It was found that this was because the local anaesthetic used was contaminated but this led to a move away from regional anaesthesia and the legacy of this catastrophe is ongoing today.

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236.: Wylde V, Lenguerrand E, Gooberman-Hill R, Beswick AD, Marques E, Noble S et al. Effect of local anaesthetic infiltration on chronic postsurgical pain after total hip and knee replacement: The APEX randomised controlled trials. Pain. 2015; 156(6):1161–70 [PMC free article: PMC4450871] [PubMed: 25659070]

237.: Yhim HY, Lee J, Lee JY, Lee JO, Bang SM. Pharmacological thromboprophylaxis and its impact on venous thromboembolism following total knee and hip arthroplasty in Korea: A nationwide population-based study. PloS One. 2017; 12(5):e0178214 [PMC free article: PMC5443574] [PubMed: 28542415]

238.: Zoric L, Cuvillon P, Alonso S, Demattei C, Vialles N, Asencio G et al. Single-shot intraoperative local anaesthetic infiltration does not reduce morphine consumption after total hip arthroplasty: A double-blinded placebo-controlled randomized study. British Journal of Anaesthesia. 2014; 112(4):722–8 [PubMed: 24431385]

239.: Zorrilla-Vaca A, Grant MC, Mathur V, Li J, Wu CL. The impact of neuraxial versus general anesthesia on the incidence of postoperative surgical site infections following knee or hip arthroplasty: A meta-analysis. Regional Anesthesia and Pain Medicine. 2016; 41(5):555–63 [PubMed: 27380106]

Appendices

Appendix A. Review protocols

Table 15. Review protocol: anaesthesia for hip joint replacement surgery (PDF, 211K)

Table 16. Health economic review protocol

Appendix B. Literature search strategies

The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual.¹⁶⁷

For more detailed information, please see the Methodology Review.

B.1. Clinical search literature search strategy

Searches were constructed using a PICO framework where population (P) terms were combined with Intervention (I) and in some cases Comparison (C) terms. Outcomes (O) are rarely used in search strategies for interventions as these concepts may not be well described in title, abstract or indexes and therefore difficult to retrieve. Search filters were applied to the searches where appropriate.

Table 17. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

Cochrane Library (Wiley) search terms

Epistemonikos search terms

B.2. Health Economics literature search strategy

Health economic evidence was identified by conducting a broad search relating to the joint replacement population in NHS Economic Evaluation Database (NHS EED – this ceased to be updated after March 2015) and the Health Technology Assessment database (HTA) with no date restrictions. NHS EED and HTA databases are hosted by the Centre for Research and Dissemination (CRD). Additional health economics searches were run in Medline and Embase.

Table 18. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

NHS EED and HTA (CRD) search terms

Appendix C. Clinical evidence selection

figure 1. Flow chart of clinical study selection for the review of anaesthesia for hip replacement surgery

Appendix D. Clinical evidence tables

Download PDF (927K)

Appendix E. Forest plots

Appendix I. Nerve block threshold analysis

A threshold analysis was conducted in order to determine the likelihood of the addition of nerve block to any anaesthetic regimen being cost effective. The analysis was deemed necessary by the committee given the lack of health economic evidence about the addition of nerve block.

I.1. Method

The analysis uses estimates of incremental cost to find what QALY or health related quality of life (HRQoL) gain is required at a given threshold of cost effectiveness. The threshold selected for this analysis was £20,000 in line with the NICE reference case. A range of incremental costs (see Table 26) driven by the time required to administer the nerve block (30 minutes, 10 minutes and 5 minutes) and if the cost of theatre time was incorporated (yes or no) were included in the analysis. The rationale for having theatre time included as a cost variable was that the committee suggested that if 2 anaesthetists are available a nerve block can be administered in the anaesthesia room, not incurring additional theatre time costs. Therefore, for scenarios where theatre time was not included, 2 consultant anaesthetists were costed in. Whereas when theatre time was included, only one consultant anaesthetist was costed in. The time required to administer a nerve block reflected the experience of the staff member in giving it, a quicker time equates to a more experienced staff member. These factors were investigated in line with the committee’s agreement that they were variable in current practice. Other resources used for nerve block administration were taken from CG124¹⁶⁸ and agreed by the committee.

The different incremental cost estimates were substituted into the equation for the incremental cost-effectiveness ratio (ICER). The equation was then rearranged (see equation below) to find the incremental QALY gain needed for the nerve block intervention to be cost effective at £20,000.

ICER = Incremental costs \div Incremental QALY

Therefore:

Incremental QALY = Incremental costs \div ICER

Following this an additional factor was analysed that was deemed variable by the committee; the time that nerve blocks have an effect upon people. The committee suggested that it could be argued the effect ranges from a matter of hours to a lifetime. The analgesic effect of a nerve block is variable but may be 8 hours on average for hip replacements. However, a 24 hour time horizon may be the most appropriate when considering acute post-operative outcomes (for example, pain, post-operative nausea and vomiting). A longer duration of effect of 10 days to 30 days may be most appropriate to account for the possible effect of anaesthetic choice on adverse clinical outcomes (for example post-operative morbidity and mortality). Lastly, an even longer time horizon would be needed if it is considered that nerve blocks have an effect upon longer term outcomes (such as chronic pain, opioid dependence and range of motion). However, in line with the pain score outcome included in the protocol, the maximum effect horizon included in the analysis was 30 days. The different QALY gains calculated as outlined above were then substituted into the QALY equation with the different time horizons (24 hours, 3 days, 10 days and 30 days). The equation was then rearranged to find the gain in HRQoL gain needed to be cost effective at a threshold of £20,000 under each scenario.

Incremental QALY = Incremental life years gained \times Incremental utility (HRQoL)

Therefore:

Incremental utility (HRQoL) = Incremental QALY \div Incremental Life years gained

If the requisite HRQoL gain was greater than 1, then it was deemed not possible for the addition of nerve blocks to be cost effective under that scenario. The assumed scale of health related quality of life was 0 to 1 where 1 is the maximum health related quality of life and 0 the least. This was chosen as the NICE Reference case states to use the EQ-5D instrument that also uses a 0 to 1 scale. The smaller the gain needed in HRQoL, the more likely the addition of nerve block was to be cost effective.

Table 26 shows the unit costs used to calculate the cost for the addition of a nerve block to an anaesthetic regimen for a the different scenarios likely to represent current practice ion the NHS

Table 26. UK 2018 cost for the addition of a nerve block to an anaesthetic regimen for primary elective joint replacement when varying administration time and the inclusion of theatre time cost

I.2. Results

The gain in QALY and gain in HRQoL needed under a range of different scenarios is shown in Table 27. For a number of scenarios; particularly when the time to administer was 30 minutes, the duration of effect was 24 hours and when theatre time was included; the likelihood of nerve blocks being cost effective was impossible given that the gain in HRQoL needed was greater than 1. When the assumptions were softened to the middle values, the gain in HRQoL was often not impossible (the gain needed was less than 1) but improbable. Finally, when time to administer was 5 minutes, the intervention effect was 30 days and when theatre time was excluded, the gain in HRQoL and therefore cost-effectiveness was more realistic.

Table 27. Threshold analysis results

I.3. Conclusions

The results indicated that for some scenarios it is impossible for nerve blocks to be cost effective, for others cost effectiveness is improbable, whilst for some it is possible.

The committee agreed that there is clinical benefit to the addition of nerve blocks, although they are only likely to be cost effective when administered by an experienced anaesthetist (leading to reduced administration time), theatre time is not included (so two anaesthetists are present) and the duration of effect is longer (as discussed, the most appropriate duration of effect is arguable). The circumstances when nerve blocks are cost effective may be found in some hospitals but not in others. Therefore the committee decided on a recommendation to consider a nerve block as an alternative to LIA.

Appendix J. Excluded studies

J.1. Excluded clinical studies

Table 28. Studies excluded from the clinical review

J.2. Excluded health economic studies

Studies that meet the review protocol population and interventions, and the economic study inclusion criteria but have not been included in the review based on applicability and/or methodological quality are summarised below with reasons for exclusion.

Table 29. Studies excluded from the health economic review

Final

Intervention evidence review underpinning recommendation 1.3.1 in the NICE guideline

This evidence review was developed by the National Guideline Centre, hosted by the Royal College of Physicians

Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and, where appropriate, their carer or guardian.

Local commissioners and providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.

NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.

Bookshelf ID: NBK561391PMID: 32881453

Table 1PICO characteristics of review question

Population	Adults having primary elective hip joint replacement
Interventions	General anaesthesia General anaesthesia with nerve block General anaesthesia with local infiltration analgesia (during or after procedure) General anaesthesia with nerve block and local infiltration analgesia (during or after procedure) Regional anaesthesia Regional anaesthesia with nerve block Regional anaesthesia with local infiltration analgesia (during or after surgery) Regional anaesthesia with nerve block and local infiltration analgesia (during or after surgery) General and regional anaesthesia General and regional anaesthesia with nerve block General and regional anaesthesia with local infiltration analgesia (during or after procedure) General and regional anaesthesia with nerve block and local infiltration analgesia (during or after procedure)
Comparison	Comparison of interventions
Outcomes	Critical Mortality: within 90 days (dichotomous) Quality of life within 30 days (continuous) Postoperative pain within 30 days (continuous) Postoperative neurocognitive decline within 30 days (dichotomous) Thromboembolic complications within 90 days (VTE; dichotomous) Hospital readmission within 30 days (dichotomous) Important Postoperative use of analgesia (dichotomous) Length of stay (continuous) Nausea within 30 days (dichotomous) Mobilisation within 24 hours after surgery
Study design	Randomised controlled trials If no well-conducted RCTs are available, then observational studies with multivariate analysis will be investigated. Multivariate analysis must account for ASA score and age.

Table 2Summary of studies included in the evidence review

Study	Details of interventions	Population	Outcomes	Comments
Regional anaesthesia with LIA versus regional anaesthesia (RCTs)
Den hartog 2015⁵⁶	All people had spinal anaesthesia using bupivacaine and propofol used for sedation. LIA was done with ropivacaine and adrenaline. There were two LIA groups, one utilising “reverse” LIA. Those not in the LIA groups received a placebo LIA with saline.	People with osteoarthritis of the hip and ASA I-II for whom primary THA has been recommended. Mean (range) age: 64 (43-84) and 69 (49-85) and 68 (55-84) N=75	Number of people with postoperative use of analgesia Nausea within 30 days	Netherlands
Dobie 2012⁶¹	All people had spinal anaesthesia. The LIA group received LIA before wound closure. A solution of levobupivacaine with adrenaline in saline was utilised. 160ml of this mixture was infiltrated into soft tissues.	People with degenerative or rheumatoid arthritis undergoing primary THA. ASA: I-III Mean (SD) age: 67 (10) and 70 (8) N=96	Postoperative pain within 30 days Postoperative use of analgesia Length of stay Mobilisation within 24 hours after surgery	UK
Hofstad 2015¹⁰¹	All people had regional through spinal anaesthesia with bupivacaine. The LIA group had ropivacaine and epinephrine in saline injected into the soft tissue as 3 specific points during surgery. An LIA placebo with saline was used in the other group.	People scheduled for elective primary THA regardless of age, ASA score, or type of prosthesis. Mean (range) age: 65 (24-88) and 66 (49-85) N=116	No relevant outcomes extracted	Norway
Liu 2011¹⁴⁰	All people had regional via spinal anaesthesia. The LIA group had morphine, bupivacaine, betamethasone, and epinephrine, mixed with saline. Injected into soft tissue three times during surgery. The non-LIA group was given LIA placebo using saline.	Adults under 80 years of age with osteoarthritis, ASA I–III, normal or low body mass index, scheduled total primary unilateral hip arthroplasty under standard spinal anaesthesia. Mean (SD) age: 79 (9) N=80	Thromboembolic complications within 90 days Nausea within 30 days	China
Lunn 2011¹⁴³	All people had regional via lumbar spinal anaesthesia with option of sedation with propofol. The LIA group had intraoperative LIA using ropivacaine.	Adults scheduled for elective unilateral primary total hip replacement. Mean (range) age: 67 (48-82) and 67 (35-87) ASA grade: I-III N=120	Number of people with postoperative use of analgesia Mobilisation within 24 hours after surgery	Denmark
Murphy 2012¹⁶⁵	All people had regional via spinal anaesthesia using bupivacaine. The LIA group had levobupivacaine in saline that was injected in various locations intraoperatively. Placebo LIA was using saline was used the other group.	People undergoing primary hip arthroplasty for osteoarthritis ASA grade: not detailed Mean (SD) age: 54 (15) and 57 (11) N=91	Postoperative use of analgesia	Republic of Ireland
Wylde 2015²³⁶	All people had regional via spinal anaesthesia using bupivacaine. The LIA group had intraoperative bupivacaine with adrenaline mixed in saline injected into the joint capsule and short external rotators, fascia, fat, and subcutaneous tissue before closure of the wound.	People undergoing primary unilateral THR for osteoarthritis ASA grade: not detailed Mean (SD) age: 66 (11) and 66 (10) N=322	Postoperative pain: no pain on admission to recovery ward Nausea within 30 days	UK
Regional anaesthesia with nerve block versus regional anaesthesia (RCTs)
Goytizolo 2016⁹⁰	All people had regional anaesthesia via combined spinal–epidural (CSE) anaesthesia. The nerve block received a lumbar plexus block.	People 60 to 100 years old with ASA score I-III who could safely undergo neuraxial anaesthesia and were scheduled for primary total hip arthroplasty. Mean (SD) age: 70 (8) and 70 (11) N=92	Postoperative use of analgesia Nausea within 30 days	Republic of Ireland
Green 2014⁹¹	All people had regional via spinal anaesthesia. The nerve block group received a psoas compartment block using bupivacaine.	People scheduled for primary total hip replacement. ASA: unclear Age: unclear N=53	Postoperative pain within 30 days Time to postoperative use of analgesia Mobilisation within 24 hours after surgery	Republic of Ireland
Regional anaesthesia with LIA versus regional anaesthesia with nerve block (RCT)
Kuchalik 2017¹³⁴	All people had regional via spinal anaesthesia using bupivacaine. The LIA group had ropivacaine, ketorloac and adrenaline injected in 3 locations during surgery. The nerve block group had a femoral nerve block using ropivacaine.	Adults 80 years old or younger with ASA I-III and scheduled for hip arthroplasty. Mean (SD) age: 64 (7) and 63 (8) N=56	Postoperative use of analgesia Nausea within 30 days	Sweden
General anaesthesia with LIA versus general anaesthesia (RCTs)
Chen 2010⁴⁰	All people had general anaesthesia with propofol and fentanyl. The LIA group had a subcutaneous injection of bupivacaine after closing of the capsule followed by regular bupivacaine.	People with osteoarthritis or osteonecrosis, aged 18 to 80 years old, undergoing unilateral THA. Mean (SD) age: 52 (13) and 54 (14) ASA status: I-III N=92	Postoperative use of analgesia Length of stay Nausea within 30 days	Taiwan
Titman 2018²²²	All people had general anaesthesia via target controlled infusion (TCI) with propofol and remifentanil. The LIA group had a mixture of ropivacaine and saline through 3 injections into the periarticular tissues.	People with ASA I-III scheduled for elective cemented THA. Mean (SD) age: 76 (7) and 77 (6) N=40	Postoperative neurocognitive decline within 30 days Postoperative use of analgesia	Sweden
Villatte 2016²³⁰	All people had general anaesthesia with standardised protocol: a combination of hypnotic, opioid and curare. The LIA group had ropivicaine and epinephrine administered twice during surgery.	People 50 to 85 years old with degenerative hip disease or rheumatoid arthritis undergoing THA Mean age: 67 ASA grade: unclear N=150	Postoperative pain within 30 days Postoperative use of analgesia Time to mobilisation	France
Zoric 2014²³⁸	All people had standardised general anaesthesia. Administration of anaesthetic drugs was left to the discretion of the attending physician. The LIA group had ropivacaine after putting in the implants. Those not in the LIA group were given a LIA placebo using saline.	People aged from 18 to 80 years old undergoing primary homolateral THA by postero-lateral incision under general anaesthesia. ASA grade: I-III Age range: 38-70 and 42-80 N=60	Number of people using postoperative NSAIDs Length of stay Nausea within 30 days Mobilisation within 24 hours after surgery	France
General anaesthesia with nerve block versus general anaesthesia (RCTs)
Kratz 2015¹³²	All people had general anaesthesia. The nerve block group had a supplemental femoral nerve block.	People undergoing hip arthroplasty ASA grade I or II Mean (SD) age: 67 (12) and 66 (14) N=80	Postoperative pain within 30 days Postoperative use of analgesia	Germany
Nicholson 2002¹⁷¹	All people had general anaesthesia induced with fentanyl and propofol or etomidate. The Nerve block group received a three-in-one nerve block (femoral nerve, lateral cutaneous nerve of thigh and obturator nerve) performed using lidocaine and bupivacaine.	Women aged over 55 years who had been amenorrhoeic for at least 2 years undergoing primary total hip replacement. Mean (SD) age: 76 (8) and 75 (8) and 78 (8) ASA grade: not detailed N=36	No relevant outcomes extracted	UK
Twyman 1990²²⁴	All people had normotensive general anaesthesia. The Nerve block group received a lumbar plexus block.	Women with osteoarthritis undergoing cemented primary total hip replacement ASA grade: not detailed Age: not detailed N=20	No relevant outcomes extracted	UK
General anaesthesia with LIA versus general anaesthesia with nerve block (RCT)
Fahs 2018⁶⁹	All people had general endotracheal anaesthesia (without neuraxial blockade). The LIA group had periarticular anaesthetic soft-tissue infiltration used ropivacaine, epinephrine, morphine, and ketorolac diluted in saline injected after component implantation and before closure, into the tissues surrounding the hip joint. The nerve block group received a psoas compartment block used ropivacaine in saline.	People with primary osteoarthritis, undergoing unilateral primary THA via DAA by the senior surgeon. Mean (SD) ASA score: 2.4 (0.5) and 2.2 (0.5) Mean (SD) age: 68 (8) and 65 (8) N=100	Quality of life within 30 days Postoperative use of analgesia Length of stay	USA
Regional anaesthesia versus general anaesthesia
RCTs
Eroglu 2005⁶⁶	The regional group had hypotensive epidural anaesthesia (HEA). A combination of an extensive epidural block and an intravenous (IV) infusion of low-dose epinephrine. The general anaesthesia group had hypotensive total IV anaesthesia (HTIVA). Anaesthesia was induced with propofol and maintained with propofol and remifentanil.	People 50 - 80 years old and ASA I-III who were scheduled for primary unilateral total hip replacement. Mean (SD) age: 64 (13) and 62 (10) N=40	No relevant outcomes extracted	Turkey
Gottschalk 2014⁸⁹	The regional group had lumbar spinal anaesthesia with bupivacaine. The general anaesthesia group was induced using sufentanil and propofol and maintained with sevoflurane.	People aged 18-75 years old with ASA physical status I - III undergoing elective total hip replacement The trial was stratified into those people with diabetes and those without diabetes. The results presented separately for each group. Mean (SD) age: 74 (6) and 71 (10) and 70 (8) and 73 (7) N=98	Postoperative use of analgesia	Germany
Harsten 2015⁹⁶	The regional group had spinal anaesthesia using bupivacaine. The general anaesthesia group had anaesthesia with remifentanil and propofol.	People 45-85 years old and ASA I-III with osteoarthritis scheduled for THA. Mean (SD) age: 68 (9), 66 (8) N=120	Length of stay Mobilisation within 24 hours after surgery	Sweden
Hogevold 2000¹⁰²	The regional group had spinal/epidural anaesthesia using bipuvicaine. The general anaesthesia group were induced by IV thiopental, pancuronium, and fentanyl.	People ASA I-II undergoing uncemented primary hip arthroplasty ASA grade I or II Mean age: 53 N=12	No relevant outcomes extracted	Norway
Modig 1987¹⁶²	The regional group had continuous lumbar epidural anaesthesia using bupivicaine and epinephrine. The general anaesthesia groups had either inhalational general anaesthesia or intermittent positive pressure ventilation (IPPV). Both induced by IV thiopentone after IV atropine.	People with advanced osteoarthritis of the hip and ASA I or II who are scheduled to undergo total hip replacement. Mean (SD) age: 67 (7) and 68 (8) and 65 (8) N=38	No relevant outcomes extracted	Sweden
Observational studies
Basques 2015¹⁸	Regional anaesthesia was always spinal anaesthesia. No details of the medications use for regional or general anaesthesia. Intervention groups were propensity score matched to control for selection bias between the spinal and general anaesthesia.	People who had primary elective total hip arthroplasty for osteoarthritis N=20936	Mortality within 90 days Propensity-adjusted multivariate logistic regression used to analyse the data.	USA American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2010 to 2012.
Donauer 2018⁶²	No details of the medications use for regional or general anaesthesia.	People who had hip replacement surgery under ICD-9 code: 81.54 Mean (SD) age: 63 (13) and 63 (11) N=1713	No outcomes extracted	Europe, Israel, and USA Analysis of people in the International PAIN OUT Registry. This takes data from institutions.
Haughom 2015⁹⁷	Regional anaesthesia was either spinal or epidural. No details of the medications use for regional or general anaesthesia.	People who had primary total hip arthroplasty. Mean age: 66 and 64 N=28857	No outcomes extracted	USA National Surgical Quality Improvement Database (NSQIP). It gathered data from 400 hospitals in 2012. This dataset was from 2005 to 2012.
Hunt 2013¹⁰⁵	Regional anaesthesia as always spinal anaesthesia. No details of the medications use for regional or general anaesthesia.	People who had primary total hip replacement surgery N=262240 (in the two intervention groups of interest)	Mortality within 90 days Cox proportional hazards model utilised to analyse the data	UK Data taken from National Joint Registry for England and Wales from April 2003 to December 2011. The NHS Personal Demographics Service provided dates of death from the Office for National Statistics.
Maurer 2007¹⁵¹	Regional anaesthesia as always spinal anaesthesia normally using bupivavaine. Propofol used to induce general anaesthesia.	People who underwent primary unilateral total hip replacement Mean (SD) age: 55 (16) and 63 (14) N=606	No outcomes extracted	USA Data from surgery at Hospital for Joint Diseases in New York, USA from January 1995 to January 1998
General and regional anaesthesia versus general anaesthesia with nerve block (RCT)
Duarte 2009⁶⁴	All people had general anaesthesia using alfentanil, propofol, and succinylcholine. The regional anaesthesia group had continuous epidural lumbar block using ropivacaine. The nerve block group received posterior lumbar plexus nerve block using ropivacaine.	Consecutive people (ASA I to III) scheduled for THA Mean (SD) age: 61 (15) and 58 (16) N=41	No relevant outcomes extracted	Brazil

Table 3RCT evidence summary: regional anaesthesia with nerve block versus regional anaesthesia

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with Regional anaesthesia with nerve block versus regional anaesthesia (95% CI)
Mortality	Not reported
Quality of life	Not reported
Postoperative pain within 30 days numerical rating scale. Scale from: 0 to 10.	53 (1 study) 2 hours after surgery	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean postoperative pain within 30 days in the control groups was 1.23	The mean postoperative pain within 30 days in the intervention groups was 1.08 lower (1.9 to 0.26 lower)
Postoperative neurocognitive decline	Not reported
Thromboembolic complications	Not reported
Hospital readmission	Not reported
Postoperative use of analgesia	92 (1 study) during hospital stay	⊕⊕⊕⊝ MODERATE² due to imprecision		The mean postoperative use of analgesia in the control groups was 71 mg	The mean postoperative use of analgesia in the intervention groups was 11 lower (25.33 lower to 3.33 higher)
Time to postoperative use of analgesia	53 (1 study)	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean time to postoperative use of analgesia in the control groups was 261 minutes	The mean time to postoperative use of analgesia in the intervention groups was 63.27 higher (24.82 lower to 151.36 higher)
Nausea within 30 days	90 (1 study) 1 days	⊕⊕⊝⊝ LOW² due to imprecision	RR 1.22 (0.62 to 2.39)	250 per 1000	55 more per 1000 (from 95 fewer to 348 more)
Mobilisation within 24 hours after surgery	53 (1 study)	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision	RR 0.95 (0.77 to 1.18)	889 per 1000	44 fewer per 1000 (from 204 fewer to 160 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 4RCT evidence summary: Regional anaesthesia with LIA versus regional anaesthesia with nerve block

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with Regional anaesthesia with LIA versus regional anaesthesia with nerve block (95% CI)
Mortality	Not reported
Quality of life	Not reported
Postoperative pain	Not reported
Postoperative neurocognitive decline	Not reported
Thromboembolic complications	Not reported
Hospital readmission	Not reported
Postoperative use of analgesia	56 (1 study) 0-24 hours after surgery	⊕⊕⊕⊝ MODERATE¹ due to imprecision		The mean postoperative use of analgesia in the control groups was 30 mg	The mean postoperative use of analgesia in the intervention groups was 13.6 lower (20.97 to 6.23 lower)
Nausea within 30 days	56 (1 study) 4-24 hours after surgery	⊕⊕⊝⊝ LOW¹ due to imprecision	RR 0.74 (0.43 to 1.29)	556 per 1000	144 fewer per 1000 (from 317 fewer to 161 more)

1: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 5RCT evidence summary: Regional anaesthesia with LIA versus regional anaesthesia

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with Regional anaesthesia with LIA versus regional anaesthesia (95% CI)

Mortality

Not reported

Quality of life

Not reported

Postoperative pain within 30 days

Visual Analogue Scale. Scale from: 0 to 10.

(1 study)

19-24 hours after surgery

⊕⊕⊝⊝

LOW¹^,²

due to risk of bias, imprecision

The mean postoperative pain within 30 days in the control groups was

0.98

The mean postoperative pain within 30 days in the intervention groups was

0.3 lower

(0.66 lower to 0.06 higher)

Postoperative pain no pain on admission to recovery ward

322

(1 study)

⊕⊕⊕⊕

HIGH

RR 1.01

(0.88 to 1.17)

698 per 1000

7 more per 1000

(from 84 fewer to 119 more)

Postoperative neurocognitive decline

Not reported

Thromboembolic complications within 90 days

(1 study)

6-12 months

⊕⊕⊝⊝

LOW²

due to imprecision

RR 0.86

(0.32 to 2.32)

179 per 1000

25 fewer per 1000

(from 122 fewer to 237 more)

Hospital readmission

Not reported

Postoperative use of analgesia mg. Scale from: 0 to 1.

183

(2 studies)

3.5 days

⊕⊝⊝⊝

VERY LOW¹^,²^,³

due to risk of bias, inconsistency, imprecision

The mean postoperative use of analgesia in the control groups was

17.5 mg

The mean postoperative use of analgesia in the intervention groups was

0.55 standard deviations lower

(1.31 lower to 0.21 higher)

Number of people with postoperative use of analgesia

201

(3 studies)

at varying in-hospital time points

⊕⊕⊝⊝

LOW²

due to imprecision

RR 0.63

(0.31 to 1.27)

185 per 1000

68 fewer per 1000

(from 127 fewer to 50 more)

Length of stay

(1 study)

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean length of stay in the control groups was

3.9 days

The mean length of stay in the intervention groups was

0.4 lower

(1.31 lower to 0.51 higher)

Nausea within 30 days

487

(4 studies)

unclear

⊕⊕⊕⊝

MODERATE²

due to imprecision

RR 0.85

(0.69 to 1.03)

449 per 1000

67 fewer per 1000

(from 139 fewer to 13 more)

Mobilisation on day 1 after surgery

(1 study)

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

RR 1.02

(0.88 to 1.19)

870 per 1000

17 more per 1000

(from 104 fewer to 165 more)

Mobilisation 8 hours after surgery

120

(1 study)

⊕⊝⊝⊝

VERY LOW²^,⁴

due to indirectness, imprecision

RR 1.57

(0.65 to 3.78)

117 per 1000

67 more per 1000

(from 41 fewer to 324 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded by 1 or 2 increments because the point estimate varies widely across studies, unexplained by subgroup analysis. Random effects (DerSimonian and Laird) model was employed.

4: Outcome is 8 hours after surgery rather than 1 day

Table 6RCT evidence summary: regional anaesthesia versus general anaesthesia

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with General anaesthesia	Risk difference with Regional anaesthesia (95% CI)
Mortality	Not reported
Quality of life	Not reported
Postoperative pain	Not reported
Postoperative neurocognitive decline	Not reported
Thromboembolic complications	Not reported
Hospital readmission	Not reported
Postoperative use of analgesia	68 (2 studies) unclear	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean postoperative use of analgesia in the control groups was 3.3 mg	The mean postoperative use of analgesia in the intervention groups was 2.89 lower (4.27 to 1.51 lower)
Length of stay	118 (1 study)	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean length of stay in the control groups was 26 hours	The mean length of stay in the intervention groups was 4 hours higher (1.33 to 6.67 higher)
Mobilisation within 24 hours after surgery	118 (1 study) 12 hours after surgery	⊕⊕⊕⊝ MODERATE¹ due to risk of bias	RR 0.98 (0.94 to 1.03)	1000 per 1000	20 fewer per 1000 (from 60 fewer to 30 more)
Mortality within 30 days of surgery	20936 (1 study) 30 days	⊕⊝⊝⊝ VERY LOW² due to imprecision	OR 1.19 (0.57 to 2.53)	1344 per 1000000	255 more per 1,000,000 (from 578 fewer to 2049 more)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 7Observational studies evidence summary: regional anaesthesia versus general anaesthesia

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Adjustment for confounding factors

Mortality within 90 days of surgery

262,240

(1 study)

VERY LOW¹

due to imprecision

Adjusted HR 0.85

(0.74 to 0.97)

Multivariate analysis using age and gender, mechanical and chemical thromboprophylaxis, and year of operation, approach, comorbidity, body-mass index, ethnic origin, and social deprivation area.

Comparison below is general anaesthesia versus regional anaesthesia as reported in the study

Mortality within 30 days of surgery

20,936

(1 study)

VERY LOW¹

due to imprecision

Adjusted OR 1.19

(0.57 to 2.53)

Propensity-adjusted multivariate logistic regression. Multivariate regression adjusted for baseline differences in patient demographic characteristics and comorbidities as well as the propensity score.

1: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 8RCT evidence summary: General anaesthesia with LIA versus general anaesthesia with nerve block

Outcomes	No of Participa nts (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participa nts (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with General anaesthesia with LIA versus general anaesthesia with nerve block (95% CI)
Mortality	Not reported
Quality of life within 30 days via Quality of Recovery QoR-40. Scale from: 40 to 200.	99 (1 study) 1 days	⊕⊕⊕⊝ MODERATE¹ due to imprecision		The mean quality of life within 30 days via quality of recovery in the control groups was 177	The mean quality of life within 30 days via quality of recovery in the intervention groups was 5.9 higher (1.05 to 10.75 higher)
Postoperative pain	Not reported
Postoperative neurocognitive decline	Not reported
Thromboembolic complications	Not reported
Hospital readmission	Not reported
Postoperative use of analgesia	99 (1 study) 1 days	⊕⊕⊕⊕ HIGH		The mean postoperative use of analgesia in the control groups was 46.2 mg	The mean postoperative use of analgesia in the intervention groups was 3.2 lower (15.42 lower to 9.02 higher)
Length of stay	99 (1 study)	⊕⊕⊕⊕ HIGH		The mean length of stay in the control groups was 1.4 days	The mean length of stay in the intervention groups was 0 higher (0.28 lower to 0.28 higher)

1: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 9RCT evidence summary: General anaesthesia with LIA versus general anaesthesia

Outcomes

No of Participants (studies) Follow up

Quality of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with Control

Risk difference with General anaesthesia with LIA versus general anaesthesia (95% CI)

Mortality

Not reported

Quality of life

Not reported

Postoperative pain within 30 days Visual Analogue Scale. Scale from: 0 to 10.

150

(1 study)

4 hours after surgery

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

The mean postoperative pain within 30 days in the control groups was

2.87

The mean postoperative pain within 30 days in the intervention groups was

0.48 lower

(0.97 lower to 0.01 higher)

Postoperative neurocognitive decline within 30 days

(1 study)

10 days

⊕⊝⊝⊝

VERY LOW¹^,⁵

due to risk of bias, imprecision

RD 0

(-0.11 to 0.11)⁴

0 per 1000

0 fewer per 1000

(from 110 fewer to 110 more)³

Postoperative use of analgesia varying methods

276

(3 studies)

2 days

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean postoperative use of analgesia in the control groups was

24 mg

The mean postoperative use of analgesia in the intervention groups was

1.94 lower

(6.2 lower to 2.33 higher)

Thromboembolic complications

Not reported

Hospital readmission

Not reported

Number of people using postoperative NSAIDs

(1 study)

while admitted in hospital

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

RR 1

(0.28 to 3.62)

138 per 1000

0 fewer per 1000

(from 99 fewer to 361 more)

Length of stay

241

(2 studies)

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean length of stay in the control groups was

6.15 days

The mean length of stay in the intervention groups was

0.1 lower

(0.4 lower to 0.2 higher)

Nausea within 30 days days

149

(2 studies)

4 days

⊕⊝⊝⊝

VERY LOW¹^,²

due to risk of bias, imprecision

RR 0.82

(0.51 to 1.32)

347 per 1000

62 fewer per 1000

(from 170 fewer to 111 more)

Mobilisation within 24 hours after surgery

(1 study)

⊕⊝⊝⊝

VERY LOW¹^,⁶

due to risk of bias, indirectness

RR 1

(0.22 to 4.55)

103 per 1000

0 fewer per 1000

(from 81 fewer to 367 more)

Time to mobilisation

150

(1 study)

⊕⊕⊕⊝

MODERATE¹

due to risk of bias

The mean time to mobilisation in the control groups was

1.9 days

The mean time to mobilisation in the intervention groups was

0.1 lower

(0.4 lower to 0.2 higher)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Absolute effect calculated using the risk difference

4: Comparative effect analysed using risk difference due to zero events in both treatment arms

5: Downgraded one increment for imprecision as it is a small study with no events.

6: Study outcome was walk in the corridor on postoperative day 2

Table 10RCT evidence summary: General anaesthesia with nerve block versus general anaesthesia

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects
Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Risk with Control	Risk difference with General anaesthesia with nerve block versus general anaesthesia (95% CI)
Mortality	Not reported
Quality of life	Not reported
Postoperative pain within 30 days Visual Analogue Scale. Scale from: 0 to 10.	52 (1 study) 1 days	⊕⊕⊝⊝ LOW¹ due to risk of bias		The mean postoperative pain within 30 days in the control groups was 4	The mean postoperative pain within 30 days in the intervention groups was 2.3 lower (3.42 to 1.18 lower)
Postoperative neurocognitive decline	Not reported
Thromboembolic complications	Not reported
Hospital readmission	Not reported
Postoperative use of analgesia	52 (1 study) unclear	⊕⊝⊝⊝ VERY LOW¹^,² due to risk of bias, imprecision		The mean postoperative use of analgesia in the control groups was 292 mg	The mean postoperative use of analgesia in the intervention groups was 223 lower (426.43 to 19.57 lower)

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 11Health economic evidence profile: LAI in addition to a standard anaesthetic regimen versus standard anaesthetic regimen only

Study	Applicability	Limitations	Other comments	Incremental cost	Incremental effects	Cost effectiveness	Uncertainty
Marques 2015¹⁴⁷ [UK]	Directly applicable^(a)	Minor limitations^(b)	A within-trial cost-utility analysis comparing a 1) standard anaesthetic regimen^(c) to 2) a LAI in addition to a standard anaesthetic regimen. The population was people who underwent a primary THR with a 12 month time horizon.	LAI in addition to a standard anaesthetic regimen saved £86 per person.	LAI in addition to a standard anaesthetic regimen gave 0.052 more QALYS per person.	LAI in addition to a standard anaesthetic regimen dominates (is less costly and more effective) standard anaesthetic alone.	A series of one way deterministic sensitivity analyses (cost of medication, inpatient stays and anomalous patients) were conducted. The dominance of the intervention was robust to all scenarios. LAI was cost effective at a threshold of £20,000 per QALY gained in over 98% of simulations.

: Abbreviations: LAI; local anaesthetic wound infiltration; QALY= quality-adjusted life years; RCT= randomised controlled trial; THR: total hip replacement;

(a): A within-trial cost-utility analysis with relevant comparators. QALYs are used as the outcome and derived using EQ-5D.

(b): Complete cost and QALY data was available for only 159/322 (49%) of participants. The final dataset therefore included imputed missing costs and outcome data. Outcomes are from a single RCT rather than a systematic review.

(c): The standard anaesthetic regimen consisted of spinal anaesthesia alone or in combination with sedation/light general anaesthesia.

Table 12Health economic evidence profile: Spinal anaesthesia versus general anaesthesia

Study	Applicability	Limitations	Other comments	Incremental cost	Incremental effects	Cost effectiveness	Uncertainty
Gonano 2006⁸⁸ [Austria]	Partially applicable^(a)	Potentially serious limitations^(b)	A cost comparison of individuals who have undergone a THR and taking part in an RCT comparing spinal anaesthesia to general anaesthesia. Time horizon is restricted to inpatient time.	Spinal anaesthesia saves £29.18 per patient	N/A	Spinal anaesthesia is cost saving compared to general anaesthesia	Four scenario analyses were conducted. These explored varying the use of muscle relaxants, fresh gas flow, and use of isoflurane instead of sevoflurane. Spinal anaesthesia being cost saving was robust to all these analyses.

: Abbreviations: RCT= randomised controlled trial; THR: Total hip replacement; TKR: Total knee replacement.

(a): A cost comparison study which does not include all relevant costs.

(b): No health outcomes are used to conduct a cost effectiveness analysis. Personnel costs are not included. The overall study population included both TKR and THR procedures but the results presented are from the THR sub-group, so the sample size is small. The time horizon only covers part of the inpatient time period.

Table 13Mean costs of anaesthesia for hip fracture in a UK hospital in 2010

Type of anaesthesia	Anaesthesia equipment (SD)	Airway equipment (SD)	Personnel (SD)	Drugs (SD)	Gases/inhalat ion agents (SD)	Total (SD)_
Spinal	£ 66.73 (30.05)	£1.81 (0)	£105.90 (0)	£19.03 (11.00)	£0.43 (0.13)	£193.81 (37.49)*
General	£108.15 (38.53)	£25.68 (2.28)	£106.76 (0)	£25.17 (11.04)	£6.26 (3.94)	£270.58 (44.68)*

: Source: Chakladar2010³⁸

Table 14UK 2018 cost for the addition of a nerve block to an anaesthetic regimen for primary elective joint replacement when varying administration time and the inclusion of theatre time cost

Extra time in theatre	Resource	Unit cost	Source
5 min	Biogel	£1.07	NHS Hospital
	Chlorhexidine	£1.08	NHS Hospital
	Vial with Lidocaine 1% 10ml ampoule	£0.38	BNF
	Vial of 0.5% Levobupivacaine (5mg/ml)	£3.88	BNF
	Syringes (10ml)	£0.06	NHS Hospital
	Filter needle	£0.23	NHS Hospital
	Regional block needle	£5.78	NHS Hospital
	Hypodermic needle	£1.35	NHS Hospital
	Cost per consultant anaesthetist (£1.80 per minute)	£9.00	PSSRU 2018
	Total cost excluding theatre time ^(a)	£31.83
	Cost of theatre time (£20.50 per min)	£102.50	CG124
	Total cost including theatre time ^(b)	£125.33
10 min	Biogel	£1.07	NHS Hospital
	Chlorhexidine	£1.08	NHS Hospital
	Vial with Lidocaine 1% 10ml ampoule	£0.38	BNF
	Vial of 0.5% Levobupivacaine (5mg/ml)	£3.88	BNF
	Syringes (10ml)	£0.06	NHS Hospital
	Filter needle	£0.23	NHS Hospital
	Regional block needle	£5.78	NHS Hospital
	Hypodermic needle	£1.35	NHS Hospital
	Cost per consultant anaesthetist (£1.80 per minute)	£18.00	PSSRU 2018
	Total cost excluding theatre time ^(a)	£49.83
	Cost of theatre time (£20.50 per min)	£205.00	CG124
	Total cost including theatre time ^(b)	£236.83	NHS Hospital
30 min	Biogel	£1.07	NHS Hospital
	Chlorhexidine	£1.08	NHS Hospital
	Vial with Lidocaine 1% 10ml ampoule	£0.38	BNF
	Vial of 0.5% Levobupivacaine (5mg/ml)	£3.88	BNF
	Syringes (10ml)	£0.06	NHS Hospital
	Filter needle	£0.23	NHS Hospital
	Regional block needle	£5.78	NHS Hospital
	Hypodermic needle	£1.35	NHS Hospital
	Cost per consultant anaesthetist (£1.80 per minute)	£54.00	PSSRU 2018
	Total cost excluding theatre time ^(a)	£121.83
	Cost of theatre time (£20.50 per min)	£615.00	CG124
	Total cost including theatre time ^(b)	£682.83	NHS Hospital

: Source: PSSRU (Personal Social Services Research Unit)⁴⁷; CG124¹⁶⁸

(a): Total costs excluding theatre time included the cost of 2 anaesthetists

(b): It was assumed that the cost of theatre time from CG124¹⁶⁸ did not include personnel costs

(c): NHS Hospital is Peterborough and Stamford Hospitals NHS Foundation Trust which provided information for CG124¹⁶⁸

Table 16Health economic review protocol

Review question	All questions – health economic evidence
Objectives	To identify health economic studies relevant to any of the review questions.
Search criteria	Populations, interventions and comparators must be as specified in the clinical review protocol above. Studies must be of a relevant health economic study design (cost–utility analysis, cost-effectiveness analysis, cost–benefit analysis, cost–consequences analysis, comparative cost analysis). Studies must not be a letter, editorial or commentary, or a review of health economic evaluations. (Recent reviews will be ordered although not reviewed. The bibliographies will be checked for relevant studies, which will then be ordered.) Unpublished reports will not be considered unless submitted as part of a call for evidence. Studies must be in English.
Search strategy	A health economic study search will be undertaken using population-specific terms and a health economic study filter – see appendix B below.
Review strategy	Studies not meeting any of the search criteria above will be excluded. Studies published before 2003, abstract-only studies and studies from low or middle-income countries (e.g. most non-OECD countries) or the USA will also be excluded. Each remaining study will be assessed for applicability and methodological limitations using the NICE economic evaluation checklist which can be found in appendix H of Developing NICE guidelines: the manual (2014).¹⁶⁷ Inclusion and exclusion criteria If a study is rated as both ‘Directly applicable’ and with ‘Minor limitations’ then it will be included in the guideline. A health economic evidence table will be completed and it will be included in the health economic evidence profile. If a study is rated as either ‘Not applicable’ or with ‘Very serious limitations’ then it will usually be excluded from the guideline. If it is excluded then a health economic evidence table will not be completed and it will not be included in the health economic evidence profile. If a study is rated as ‘Partially applicable’, with ‘Potentially serious limitations’ or both then there is discretion over whether it should be included. Where there is discretion The health economist will make a decision based on the relative applicability and quality of the available evidence for that question, in discussion with the guideline committee if required. The ultimate aim is to include health economic studies that are helpful for decision-making in the context of the guideline and the current NHS setting. If several studies are considered of sufficiently high applicability and methodological quality that they could all be included, then the health economist, in discussion with the committee if required, may decide to include only the most applicable studies and to selectively exclude the remaining studies. All studies excluded on the basis of applicability or methodological limitations will be listed with explanation in the excluded health economic studies appendix below. The health economist will be guided by the following hierarchies. Setting: UK NHS (most applicable). OECD countries with predominantly public health insurance systems (for example, France, Germany, Sweden). OECD countries with predominantly private health insurance systems (for example, Switzerland). Studies set in non-OECD countries or in the USA will be excluded before being assessed for applicability and methodological limitations. Health economic study type: Cost–utility analysis (most applicable). Other type of full economic evaluation (cost–benefit analysis, cost-effectiveness analysis, cost–consequences analysis). Comparative cost analysis. Non-comparative cost analyses including cost-of-illness studies will be excluded before being assessed for applicability and methodological limitations. Year of analysis: The more recent the study, the more applicable it will be. Studies published in 2003 or later but that depend on unit costs and resource data entirely or predominantly from before 2003 will be rated as ‘Not applicable’. Studies published before 2003 will be excluded before being assessed for applicability and methodological limitations. Quality and relevance of effectiveness data used in the health economic analysis: The more closely the clinical effectiveness data used in the health economic analysis match with the outcomes of the studies included in the clinical review the more useful the analysis will be for decision-making in the guideline.

Table 17Database date parameters and filters used

Database	Dates searched	Search filter used
Medline (OVID)	1946 – 01 May 2019	Exclusions Randomised controlled trials Systematic review studies Observational studies
Embase (OVID)	1974 – 01 May 2019	Exclusions Randomised controlled trials Systematic review studies Observational studies
The Cochrane Library (Wiley)	Cochrane Reviews to 2019 Issue 5 of 12 CENTRAL to 2019 Issue 5 of 12	None
Epistemonikos	Inception – 01 May 2019	None

Medline (Ovid) search terms

1.	arthroplasty/ or arthroplasty, replacement/ or arthroplasty, replacement, hip/ or arthroplasty, replacement, knee/ or arthroplasty, replacement, shoulder/ or hemiarthroplasty/
2.	joint prosthesis/ or hip prosthesis/ or knee prosthesis/ or shoulder prosthesis/
3.	((joint* or knee* or shoulder* or hip) adj5 (surger or replace* or prosthe* or endoprosthe* or implant* or artificial or arthroplast* or hemiarthroplast*)).ti,ab.
4.	or/1-3
5.	letter/
6.	editorial/
7.	news/
8.	exp historical article/
9.	Anecdotes as Topic/
10.	comment/
11.	case report/
12.	(letter or comment*).ti.
13.	or/5-12
14.	randomized controlled trial/ or random*.ti,ab.
15.	13 not 14
16.	animals/ not humans/
17.	exp Animals, Laboratory/
18.	exp Animal Experimentation/
19.	exp Models, Animal/
20.	exp Rodentia/
21.	(rat or rats or mouse or mice).ti.
22.	or/15-21
23.	4 not 22
24.	limit 23 to English language
25.	exp Anesthesia/
26.	((an?esthet* or an?esthesia) adj4 (regional* or local* or general or spinal or epidural)).ti,ab.
27.	Nerve Block/
28.	((nerve* or neurax* or regional or peripheral) adj3 block).ti,ab.
29.	((plexus or sciatic* or interscalene or femor* or tibia* or posterior or obturator or fascia iliaca) adj3 block).ti,ab.
30.	(CNB or PNB or FNB or TNB or ONB or LPB or ISBB or FIB or LIA).ti,ab.
31.	((periarticular or local*) adj2 infiltration).ti,ab.
32.	or/25-31
33.	24 and 32
34.	randomized controlled trial.pt.
35.	controlled clinical trial.pt.
36.	randomi#ed.ti,ab.
37.	placebo.ab.
38.	randomly.ti,ab.
39.	Clinical Trials as topic.sh.
40.	trial.ti.
41.	or/34-40
42.	Meta-Analysis/
43.	exp Meta-Analysis as Topic/
44.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
45.	((systematic* or evidence) adj3 (review or overview*)).ti,ab.
46.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
47.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
48.	(search* adj4 literature).ab.
49.	(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.
50.	cochrane.jw.
51.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
52.	or/42-51
53.	Epidemiologic studies/
54.	Observational study/
55.	exp Cohort studies/
56.	(cohort adj (study or studies or analys* or data)).ti,ab.
57.	((follow up or observational or uncontrolled or non randomi#ed or epidemiologic*) adj (study or studies or data)).ti,ab.
58.	((longitudinal or retrospective or prospective or cross sectional) and (study or studies or review or analys* or cohort* or data)).ti,ab.
59.	Controlled Before-After Studies/
60.	Historically Controlled Study/
61.	Interrupted Time Series Analysis/
62.	(before adj2 after adj2 (study or studies or data)).ti,ab.
63.	or/54-63
64.	exp case control study/
65.	case control*.ti,ab.
66.	or/65-66
67.	64 or 67
68.	Cross-sectional studies/
69.	(cross sectional and (study or studies or review or analys* or cohort* or data)).ti,ab.
70.	or/69-70
71.	64 or 71
72.	64 or 67 or 71
73.	33 and (41 or 52 or 72)

Embase (Ovid) search terms

1.	arthroplasty/ or replacement arthroplasty/ or hip replacement/ or knee replacement/ or shoulder replacement/ or hemiarthroplasty/
2.	joint prosthesis/ or hip prosthesis/ or knee prosthesis/ or shoulder prosthesis/
3.	((joint* or knee* or shoulder* or hip) adj5 (surger or replace* or prosthe* or endoprosthe* or implant* or artificial or arthroplast* or hemiarthroplast*)).ti,ab.
4.	or/1-3
5.	letter.pt. or letter/
6.	note.pt.
7.	editorial.pt.
8.	case report/ or case study/
9.	(letter or comment*).ti.
10.	or/5-9
11.	randomized controlled trial/ or random*.ti,ab.
12.	10 not 11
13.	animal/ not human/
14.	nonhuman/
15.	exp Animal Experiment/
16.	exp Experimental Animal/
17.	animal model/
18.	exp Rodent/
19.	(rat or rats or mouse or mice).ti.
20.	or/12-19
21.	4 not 20
22.	limit 21 to English language
23.	*anesthesia/ or general anesthesia/ or regional anesthesia/
24.	((an?esthet* or an?esthesia) adj4 (regional* or local* or general or spinal or epidural)).ti,ab.
25.	nerve block/
26.	((nerve* or neurax* or regional or peripheral) adj3 block).ti,ab.
27.	((plexus or sciatic* or interscalene or femor* or tibia* or posterior or obturator or fascia iliaca) adj3 block).ti,ab.
28.	(CNB or PNB or FNB or TNB or ONB or LPB or ISBB or FIB or LIA).ti,ab.
29.	((periarticular or local*) adj2 infiltration).ti,ab.
30.	or/23-29
31.	22 and 30
32.	random*.ti,ab.
33.	factorial*.ti,ab.
34.	(crossover* or cross over*).ti,ab.
35.	((doubl* or singl) adj blind).ti,ab.
36.	(assign* or allocat* or volunteer* or placebo*).ti,ab.
37.	crossover procedure/
38.	single blind procedure/
39.	randomized controlled trial/
40.	double blind procedure/
41.	or/32-40
42.	systematic review/
43.	meta-analysis/
44.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
45.	((systematic* or evidence) adj3 (review or overview*)).ti,ab.
46.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
47.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
48.	(search* adj4 literature).ab.
49.	(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.
50.	cochrane.jw.
51.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
52.	or/42-51
53.	Clinical study/
54.	Observational study/
55.	family study/
56.	longitudinal study/
57.	retrospective study/
58.	prospective study/
59.	cohort analysis/
60.	follow-up/
61.	cohort*.ti,ab.
62.	61 and 62
63.	(cohort adj (study or studies or analys* or data)).ti,ab.
64.	((follow up or observational or uncontrolled or non randomi#ed or epidemiologic*) adj (study or studies or data)).ti,ab.
65.	((longitudinal or retrospective or prospective or cross sectional) and (study or studies or review or analys* or cohort* or data)).ti,ab.
66.	(before adj2 after adj2 (study or studies or data)).ti,ab.
67.	or/54-60,63-67
68.	exp case control study/
69.	case control*.ti,ab.
70.	or/69-70
71.	68 or 71
72.	cross-sectional study/
73.	(cross sectional and (study or studies or review or analys* or cohort* or data)).ti,ab.
74.	or/73-74
75.	68 or 75
76.	68 or 71 or 75
77.	31 and (41 or 52 or 76)

Cochrane Library (Wiley) search terms

#1.	MeSH descriptor: [Arthroplasty] this term only
#2.	MeSH descriptor: [Arthroplasty, Replacement] this term only
#3.	MeSH descriptor: [Arthroplasty, Replacement, Hip] this term only
#4.	MeSH descriptor: [Arthroplasty, Replacement, Knee] this term only
#5.	MeSH descriptor: [Arthroplasty, Replacement, Shoulder] this term only
#6.	MeSH descriptor: [Hemiarthroplasty] this term only
#7.	(or #1-#6)
#8.	MeSH descriptor: [Joint Prosthesis] this term only
#9.	MeSH descriptor: [Hip Prosthesis] this term only
#10.	MeSH descriptor: [Knee Prosthesis] this term only
#11.	MeSH descriptor: [Shoulder Prosthesis] this term only
#12.	(or #8-#11)
#13.	((joint* or knee* or shoulder* or hip) near/5 (surger or replace* or prosthe* or endoprosthe* or implant* or artificial or arthroplast* or hemiarthroplast*)):ti,ab
#14.	(or #7, #12-#13)
#15.	MeSH descriptor: [Anesthesia] explode all trees
#16.	((anaesthet* or anesthet* or anaesthesia or anesthesia) near/4 (regional* or local* or general or spinal or epidural)):ti,ab
#17.	MeSH descriptor: [Nerve Block] this term only
#18.	((nerve* or neurax* or regional or peripheral) near/3 block):ti,ab
#19.	((plexus or sciatic* or interscalene or femor* or tibia* or posterior or obturator or fascia iliaca) near/3 block):ti,ab
#20.	(CNB or PNB or FNB or TNB or ONB or LPB or ISBB or FIB or LIA):ti,ab
#21.	((periarticular or local*) near/2 infiltration):ti,ab
#22.	(or #15-#21)
#23.	#14 and #22

Epistemonikos search terms

((joint* OR knee* OR shoulder* OR hip*) AND (surger* OR replace* OR prosthe* OR endoprosthe* OR implant* OR artificial OR arthroplast* OR hemiarthroplast*)) AND (((an?esthet* OR an?esthesia) AND (regional* OR local* OR general OR spinal OR epidural)) OR ((nerve* OR neurax* OR regional OR peripheral*) AND block*) OR ((plexus OR sciatic* OR interscalene OR femor* OR tibia* OR posterior OR obturator OR fascia iliaca) AND block) OR (CNB OR PNB OR FNB OR TNB OR ONB OR LPB OR ISBB OR FIB OR LIA) OR ((periarticular OR local*) AND infiltration)) [Filters: protocol=no, classification=systematic-review]

Table 18Database date parameters and filters used

Database

Dates searched

Search filter used

Medline

2014 – 01 May 2019

Exclusions

Health economics studies

Embase

2014 – 01 May 2019

Exclusions

Health economics studies

Centre for Research and Dissemination (CRD)

HTA - Inception – 01 May 2019

NHSEED - Inception to March 2015

None

Medline (Ovid) search terms

1.	arthroplasty/ or arthroplasty, replacement/ or arthroplasty, replacement, hip/ or arthroplasty, replacement, knee/ or arthroplasty, replacement, shoulder/ or hemiarthroplasty/
2.	joint prosthesis/ or hip prosthesis/ or knee prosthesis/ or shoulder prosthesis/
3.	((joint* or knee* or shoulder* or hip) adj5 (surger or replace* or prosthe* or endoprosthe* or implant* or artificial or arthroplast* or hemiarthroplast*)).ti,ab.
4.	or/1-3
5.	letter/
6.	editorial/
7.	news/
8.	exp historical article/
9.	Anecdotes as Topic/
10.	comment/
11.	case report/
12.	(letter or comment*).ti.
13.	or/5-12
14.	randomized controlled trial/ or random*.ti,ab.
15.	13 not 14
16.	animals/ not humans/
17.	exp Animals, Laboratory/
18.	exp Animal Experimentation/
19.	exp Models, Animal/
20.	exp Rodentia/
21.	(rat or rats or mouse or mice).ti.
22.	or/15-21
23.	4 not 22
24.	limit 23 to English language
25.	Economics/
26.	Value of life/
27.	exp “Costs and Cost Analysis”/
28.	exp Economics, Hospital/
29.	exp Economics, Medical/
30.	Economics, Nursing/
31.	Economics, Pharmaceutical/
32.	exp “Fees and Charges”/
33.	exp Budgets/
34.	budget*.ti,ab.
35.	cost*.ti.
36.	(economic* or pharmaco?economic*).ti.
37.	(price* or pricing*).ti,ab.
38.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
39.	(financ* or fee or fees).ti,ab.
40.	(value adj2 (money or monetary)).ti,ab.
41.	or/25-40
42.	24 and 41

Embase (Ovid) search terms

1.	arthroplasty/ or replacement arthroplasty/ or hip replacement/ or knee replacement/ or shoulder replacement/ or hemiarthroplasty/
2.	joint prosthesis/ or hip prosthesis/ or knee prosthesis/ or shoulder prosthesis/
3.	((joint* or knee* or shoulder* or hip) adj5 (surger or replace* or prosthe* or endoprosthe* or implant* or artificial or arthroplast* or hemiarthroplast*)).ti,ab.
4.	or/1-3
5.	letter.pt. or letter/
6.	note.pt.
7.	editorial.pt.
8.	case report/ or case study/
9.	(letter or comment*).ti.
10.	or/5-9
11.	randomized controlled trial/ or random*.ti,ab.
12.	10 not 11
13.	animal/ not human/
14.	nonhuman/
15.	exp Animal Experiment/
16.	exp Experimental Animal/
17.	animal model/
18.	exp Rodent/
19.	(rat or rats or mouse or mice).ti.
20.	or/12-19
21.	4 not 20
22.	limit 21 to English language
23.	health economics/
24.	exp economic evaluation/
25.	exp health care cost/
26.	exp fee/
27.	budget/
28.	funding/
29.	budget*.ti,ab.
30.	cost*.ti.
31.	(economic* or pharmaco?economic*).ti.
32.	(price* or pricing*).ti,ab.
33.	(cost* adj2 (effective* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.
34.	(financ* or fee or fees).ti,ab.
35.	(value adj2 (money or monetary)).ti,ab.
36.	or/23-35
37.	22 and 36

NHS EED and HTA (CRD) search terms

#1.	MeSH DESCRIPTOR arthroplasty
#2.	MeSH DESCRIPTOR arthroplasty, replacement
#3.	MeSH DESCRIPTOR arthroplasty, replacement, hip
#4.	MeSH DESCRIPTOR arthroplasty, replacement, knee
#5.	MeSH DESCRIPTOR arthroplasty, replacement, shoulder
#6.	MeSH DESCRIPTOR hemiarthroplasty
#7.	MeSH DESCRIPTOR joint prosthesis
#8.	MeSH DESCRIPTOR hip prosthesis
#9.	MeSH DESCRIPTOR knee prosthesis
#10.	MeSH DESCRIPTOR shoulder prosthesis
#11.	(((joint* or knee* or shoulder* or hip) adj5 (surger or replace* or prosthe* or endoprosthe* or implant* or artificial or arthroplast* or hemiarthroplast*)))
#12.	(#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11) IN NHSEED
#13.	(#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11) IN HTA

figure 1Flow chart of clinical study selection for the review of anaesthesia for hip replacement surgery

Figure 2Postoperative pain within 30 days

Figure 3Postoperative use of analgesia

Figure 4Time to postoperative use of analgesia

Figure 5Nausea within 30 days

Figure 6Mobilisation within 24 hours after surgery

Figure 7Postoperative use of analgesia

Figure 8Nausea within 30 days

Figure 9Postoperative pain within 30 days

Figure 10Postoperative pain: no pain on admission to recovery ward

Figure 11Thromboembolic complications within 90 days

Figure 12Postoperative use of analgesia

Figure 13Number of people with postoperative use of analgesia

Figure 14Length of stay

Figure 15Nausea within 30 days

Figure 16Mobilisation within 24 hours after surgery

Figure 17Mortality within 90 days of surgery

Figure 18Mortality within 30 days of surgery

Figure 19Postoperative use of analgesia

Figure 20Length of stay

Figure 21Mobilisation within 24 hours after surgery

Figure 22Quality of life within 30 days

Figure 23Postoperative use of analgesia

Figure 24Length of stay

Figure 25Postoperative pain within 30 days

Figure 26Postoperative neurocognitive decline within 30 days

Figure 27Postoperative use of analgesia

Figure 28Number of people using postoperative NSAIDs

Figure 29Length of stay

Figure 30Nausea within 30 days

Figure 31Mobilisation within 24 hours after surgery

Figure 32Time to mobilisation

Figure 33Postoperative pain within 30 days

Figure 34Postoperative use of analgesia

Table 19Clinical evidence profile: regional anaesthesia with nerve block versus regional anaesthesia

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Regional anaesthesia with nerve block versus regional anaesthesia	Control	Relative (95% CI)	Absolute	Quality	Importance
Postoperative pain within 30 days (follow-up mean 2 hours after surgery; measured with: numerical rating scale; range of scores: 0-10; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	26	27	-	MD 1.08 lower (1.9 to 0.26 lower)	⨁◯◯◯ VERY LOW	CRITICAL
Postoperative use of analgesia (follow-up during hospital stay; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious²	none	46	46	-	MD 11 lower (25.33 lower to 3.33 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Time to postoperative use of analgesia (Better indicated by higher values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	26	27	-	MD 63.27 higher (24.82 lower to 151.36 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Nausea within 30 days (follow-up mean 1 days)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious²	none	14/46 (30.4%)	11/44 (25%)	RR 1.22 (0.62 to 2.39)	55 more per 1000 (from 95 fewer to 348 more)	⨁⨁◯◯ LOW	IMPORTANT
Mobilisation within 24 hours after surgery
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	22/26 (84.6%)	24/27 (88.9%)	RR 0.95 (0.77 to 1.18)	44 fewer per 1000 (from 204 fewer to 160 more)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 20Clinical evidence profile: regional anaesthesia with LIA versus regional anaesthesia with nerve block

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Regional anaesthesia with LIA versus regional anaesthesia with nerve block	Control	Relative (95% CI)	Absolute	Quality	Importance
Postoperative use of analgesia (follow-up 0-24 hours after surgery; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	29	27	-	MD 13.6 lower (20.97 to 6.23 lower)	⨁⨁⨁◯ MODERATE	IMPORTANT
Nausea within 30 days days (follow-up 4-24 hours after surgery)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious¹	none	12/29 (41.4%)	15/27 (55.6%)	RR 0.74 (0.43 to 1.29)	144 fewer per 1000 (from 317 fewer to 161 more)	⨁⨁◯◯ LOW	IMPORTANT

1: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 21Clinical evidence profile: regional anaesthesia with LIA versus regional anaesthesia

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Regional anaesthesia with LIA versus regional anaesthesia	Control	Relative (95% CI)	Absolute	Quality	Importance
Postoperative pain within 30 days (follow-up 19-24 hours after surgery; measured with: Visual Analogue Scale; range of scores: 0-10; Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	serious²	none	46	46	-	MD 0.3 lower (0.66 lower to 0.06 higher)	⨁⨁◯◯ LOW	CRITICAL
Postoperative pain (assessed with: no pain on admission to recovery ward)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	115/163 (70.6%)	111/159 (69.8%)	RR 1.01 (0.88 to 1.17)	7 more per 1000 (from 84 fewer to 119 more)	⨁⨁⨁⨁ HIGH	CRITICAL
Thromboembolic complications within 90 days (follow-up mean 6-12 months)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious²	none	6/39 (15.4%)	7/39 (17.9%)	RR 0.86 (0.32 to 2.32)	25 fewer per 1000 (from 122 fewer to 237 more)	⨁⨁◯◯ LOW	CRITICAL
Postoperative use of analgesia (follow-up mean 3.5 days; measured with: mg; range of scores: 0-1; Better indicated by lower values)
2	randomised trials	serious¹	very serious³	no serious indirectness	serious²	none	91	92	-	SMD 0.55 lower (1.31 lower to 0.21 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Number of people with postoperative use of analgesia (follow-up at varying in-hospital time points)
3	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious²	none	13/109 (11.9%)	17/92 (18.5%)	RR 0.63 (0.31 to 1.27)	68 fewer per 1000 (from 127 fewer to 50 more)	⨁⨁◯◯ LOW	IMPORTANT
Length of stay (Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	46	46	-	MD 0.4 lower (1.31 lower to 0.51 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Nausea within 30 days (follow-up unclear)
4	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious²	none	92/242 (38%)	110/245 (44.9%)	RR 0.85 (0.69 to 1.03)	67 fewer per 1000 (from 139 fewer to 13 more)	⨁⨁⨁◯ MODERATE	IMPORTANT
Mobilisation on day 1 after surgery
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	41/46 (89.1%)	40/46 (87%)	RR 1.02 (0.88 to 1.19)	17 more per 1000 (from 104 fewer to 165 more)	⨁⨁⨁◯ MODERATE	IMPORTANT
Mobilisation 8 hours after surgery
1	randomised trials	no serious risk of bias	no serious inconsistency	serious⁴	very serious²	none	11/60 (18.3%)	7/60 (11.7%)	RR 1.57 (0.65 to 3.78)	67 more per 1000 (from 41 fewer to 324 more)	⨁◯◯◯ VERY LOW	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded by 1 or 2 increments because the point estimate varies widely across studies, unexplained by subgroup analysis. Random effects (DerSimonian and Laird) model was employed.

4: Outcome is 8 hours after surgery rather than 1 day

Table 22Clinical evidence profile: regional anaesthesia versus general anaesthesia

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Regional anaesthesia	General anaesthesia	Relative (95% CI)	Absolute	Quality	Importance
Postoperative use of analgesia (measured with: Unclear follow-up time; Better indicated by lower values)
2	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	33	35	-	MD 2.89 lower (4.27 to 1.51 lower)	⨁◯◯◯ VERY LOW	IMPORTANT
Length of stay (Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	58	60	-	MD 4 higher (1.33 to 6.67 higher)	⨁◯◯◯ VERY LOW	IMPORTANT
Mobilisation within 24 hours after surgery (follow-up mean 12 hours)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	57/58 (98.3%)	60/60 (100%)	RR 0.98 (0.94 to 1.03)	20 fewer per 1000 (from 60 fewer to 30 more)	⨁⨁⨁◯ MODERATE	IMPORTANT
Mortality within 30 days of surgery (follow-up 30 days)
1	observational studies	no serious risk of bias	no serious inconsistency	no serious indirectness	very serious²	none			OR 1.19 (0.57 to 2.53)		⨁◯◯◯ VERY LOW	CRITICAL
Mortality within 90 days of surgery (follow-up 30 days)
1	observational studies	no serious risk of bias	no serious inconsistency	no serious indirectness	serious²	none	-	-	Adjusted HR 0.85 (0.74 to 0.97)	-	⨁◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Table 23Clinical evidence profile: general anaesthesia with LIA versus general anaesthesia with nerve block

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	General anaesthesia with LIA versus general anaesthesia with nerve block	Control	Relative (95% CI)	Absolute	Quality	Importance
Quality of life within 30 days via Quality of Recovery (follow-up mean 1 days; measured with: QoR-40; range of scores: 40-200; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	serious¹	none	50	49	-	MD 5.9 higher (1.05 to 10.75 higher)	⨁⨁⨁◯ MODERATE
Postoperative use of analgesia (follow-up mean 1 days; Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	50	49	-	MD 3.2 lower (15.42 lower to 9.02 higher)	⨁⨁⨁⨁ HIGH	IMPORTANT
Length of stay (Better indicated by lower values)
1	randomised trials	no serious risk of bias	no serious inconsistency	no serious indirectness	no serious imprecision	none	50	49	-	MD 0 higher (0.28 lower to 0.28 higher)	⨁⨁⨁⨁ HIGH	IMPORTANT

1: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs

Table 24Clinical evidence profile: general anaesthesia with LIA versus general anaesthesia

Quality assessment							No of patients		Effect		Quality	Importance
No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	General anaesthesia with LIA versus general anaesthesia	Control	Relative (95% CI)	Absolute	Quality	Importance
Postoperative pain within 30 days (follow-up mean 4 hours after surgery; measured with: Visual Analogue Scale; range of scores: 0-10; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	75	75	-	MD 0.48 lower (0.97 lower to 0.01 higher)	⨁◯◯◯ VERY LOW	CRITICAL
Postoperative neurocognitive decline within 30 days (follow-up mean 10 days)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious³	none	0/19 (0%)	0/16 (0%)	See comment⁴	0 fewer per 1000 (from 110 fewer to 110 more)⁵	⨁◯◯◯ VERY LOW	CRITICAL
Postoperative use of analgesia (follow-up mean 2 days; measured with: varying methods; Better indicated by lower values)
3	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	139	137	-	MD 1.94 lower (6.2 lower to 2.33 higher)	⨁⨁⨁◯ MODERATE	CRITICAL
Number of people using postoperative NSAIDs (follow-up while admitted in hospital)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	very serious²	none	4/29 (13.8%)	4/29 (13.8%)	RR 1 (0.28 to 3.62)	0 fewer per 1000 (from 99 fewer to 361 more)	⨁◯◯◯ VERY LOW	IMPORTANT
Length of stay (Better indicated by lower values)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	120	121	-	MD 0.1 lower (0.4 lower to 0.2 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT
Nausea within 30 days days (follow-up mean 4 days)
2	randomised trials	serious¹	no serious inconsistency	no serious indirectness	very serious²	none	21/74 (28.4%)	26/75 (34.7%)	RR 0.82 (0.51 to 1.32)	62 fewer per 1000 (from 170 fewer to 111 more)	⨁◯◯◯ VERY LOW	IMPORTANT
Mobilisation within 24 hours after surgery
1	randomised trials	very serious¹	no serious inconsistency	serious⁶	no serious imprecision	none	3/29 (10.3%)	3/29 (10.3%)	RR 1 (0.22 to 4.55)	0 fewer per 1000 (from 81 fewer to 367 more)	⨁◯◯◯ VERY LOW	IMPORTANT
Time to mobilisation (Better indicated by lower values)
1	randomised trials	serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	75	75	-	MD 0.1 lower (0.4 lower to 0.2 higher)	⨁⨁⨁◯ MODERATE	IMPORTANT

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

3: Downgraded one increment for imprecision as it is a small study with no events.

4: Comparative effect analysed using risk difference due to zero events in both treatment arms

5: Absolute effect calculated using the risk difference

6: Study outcome was walk in the corridor on postoperative day 2

Table 25Clinical evidence profile: general anaesthesia with nerve block versus general anaesthesia

No of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	General anaesthesia with nerve block versus general anaesthesia	Control	Relative (95% CI)	Absolute
Postoperative pain within 30 days (follow-up mean 1 days; measured with: Visual Analogue Scale; range of scores: 0-10; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	no serious imprecision	none	26	26	-	MD 2.3 lower (3.42 to 1.18 lower)	⨁⨁◯◯ LOW	CRITICAL
Postoperative use of analgesia (follow-up unclear; Better indicated by lower values)
1	randomised trials	very serious¹	no serious inconsistency	no serious indirectness	serious²	none	26	26	-	MD 223 lower (426.43 to 19.57 lower)	⨁◯◯◯ VERY LOW	CRITICAL

1: Downgraded by 1 increment if the majority of the evidence was at high risk of bias and downgraded by 2 increments if the majority of the evidence was at very high risk of bias.

2: Downgraded by 1 increment if the confidence interval crossed 1 MID or by 2 increments if the confidence interval crossed both MIDs.

Figure 35Flow chart of health economic study selection for the guideline

a) Non-relevant population, intervention, comparison, design or setting; non-English language

b) One study was applicable to both Q3.1 and Q3.2

Table 26UK 2018 cost for the addition of a nerve block to an anaesthetic regimen for primary elective joint replacement when varying administration time and the inclusion of theatre time cost

Extra time in theatre	Resource	Unit cost	Source
5 min	Biogel	£1.07	NHS Hospital
	Chlorhexidine	£1.08	NHS Hospital
	Vial with Lidocaine 1% 10ml ampoule	£0.38	BNF
	Vial of 0.5% Levobupivacaine (5mg/ml)	£3.88	BNF
	Syringes (10ml)	£0.06	NHS Hospital
	Filter needle	£0.23	NHS Hospital
	Regional block needle	£5.78	NHS Hospital
	Hypodermic needle	£1.35	NHS Hospital
	Cost per consultant anaesthetist (£1.80 per minute)	£9.00	PSSRU 2018
	Total cost excluding theatre time ^(a)	£31.83
	Cost of theatre time (£20.50 per min)	£102.50	CG124
	Total cost including theatre time ^(b)	£125.33
10 min	Biogel	£1.07	NHS Hospital
	Chlorhexidine	£1.08	NHS Hospital
	Vial with Lidocaine 1% 10ml ampoule	£0.38	BNF
	Vial of 0.5% Levobupivacaine (5mg/ml)	£3.88	BNF
	Syringes (10ml)	£0.06	NHS Hospital
	Filter needle	£0.23	NHS Hospital
	Regional block needle	£5.78	NHS Hospital
	Hypodermic needle	£1.35	NHS Hospital
	Cost per consultant anaesthetist (£1.80 per minute)	£18.00	PSSRU 2018
	Total cost excluding theatre time ^(a)	£49.83
	Cost of theatre time (£20.50 per min)	£205.00	CG124
	Total cost including theatre time ^(b)	£236.83	NHS Hospital
30 min	Biogel	£1.07	NHS Hospital
	Chlorhexidine	£1.08	NHS Hospital
	Vial with Lidocaine 1% 10ml ampoule	£0.38	BNF
	Vial of 0.5% Levobupivacaine (5mg/ml)	£3.88	BNF
	Syringes (10ml)	£0.06	NHS Hospital
	Filter needle	£0.23	NHS Hospital
	Regional block needle	£5.78	NHS Hospital
	Hypodermic needle	£1.35	NHS Hospital
	Cost per consultant anaesthetist (£1.80 per minute)	£54.00	PSSRU 2018
	Total cost excluding theatre time ^(a)	£121.83
	Cost of theatre time (£20.50 per min)	£615.00	CG124
	Total cost including theatre time ^(b)	£682.83	NHS Hospital

: Source: PSSRU (Personal Social Services Research Unit)⁴⁷; CG124¹⁶⁸

(a): Total costs excluding theatre time included the cost of 2 anaesthetists

(b): It was assumed that the cost of theatre time from CG124 did not include personnel costs

(c): NHS hospital is Peterborough and Stamford Hospitals NHS Foundation Trust which provided information for CG124¹⁶⁸

Table 27Threshold analysis results

Time to add nerve block	Theatre time included	Incremental cost	Gain in QALY needed	Health related quality of life gain needed in:
Time to add nerve block	Theatre time included	Incremental cost	Gain in QALY needed	24 hours	3 days	10 days	30 days
30 mins	Yes	£682.83	0.034	12.462	4.154	1.246	0.415
10 mins	Yes	£236.83	0.012	4.322	1.441	0.432	0.144
5 mins	Yes	£125.33	0.006	2.287	0.762	0.229	0.076
30 mins	No	£121.83	0.006	2.223	0.741	0.222	0.074
10 mins	No	£49.83	0.002	0.909	0.303	0.091	0.030
5 mins	No	£31.83	0.002	0.581	0.194	0.058	0.019

Table 28Studies excluded from the clinical review

Study	Exclusion reason
Affas 2016¹	Unclear if the study population is people undergoing primary arthroplasty
Aguirre 2012²	Unclear if the study population is people undergoing primary hip arthroplasty
Ahmed 2017³	Not review population
Aksoy 2014⁴	Unclear if the study population is people undergoing primary arthroplasty
Andersen 2007⁶	Unclear if the study population is people undergoing primary hip arthroplasty
Andersen 2007⁷	Unclear if the study population is people undergoing primary arthroplasty
Andersen 2011⁹	Unclear if the study population is people undergoing primary hip arthroplasty
Andersen 2014⁸	Systematic review with different inclusion criteria however included studies were checked for this review
Andersen 2015⁵	Incorrect interventions
Anonymous 2018¹⁰	Correction of excluded paper
Asajima 1998¹¹	Not in English
Atchabahian 2015¹²	Systematic review with different inclusion criteria however included studies were checked for this review
Axelsson 2005¹³	Unclear if the study population is people undergoing primary arthroplasty
Babaiants 2008¹⁴	Not in English
Bakalov 2016¹⁵	Unable to obtain
Bang 2016¹⁶	Unclear if the study population is people undergoing primary hip arthroplasty
Banwait 2012¹⁷	Unclear if the study population is people undergoing primary arthroplasty
Becchi 2008¹⁹	Incorrect interventions
Bertini 1995²¹	Not in English
Bertini 2001²⁰	Unclear if the study population is people undergoing primary arthroplasty
Bianconi 2003²²	Not review population
Biboulet 2004²³	Unclear if the study population is people undergoing primary arthroplasty
Bichel 1998²⁴	Not in English
Bogoch 2002²⁵	Not review population
Borghi 2002²⁶	Unclear if the study population is people undergoing primary hip arthroplasty
Borghi 2002²⁸	Not in English
Borghi 2005²⁷	Unclear if the study population is people undergoing primary hip arthroplasty
Borisov 2012²⁹	Not in English
Brinker 1997³⁰	Incorrect study design
Brueckner 1997³²	Conference abstract
Brueckner 2003³¹	Incorrect study design
Burton 2019³³	Unclear if the study population is people undergoing primary hip arthroplasty
Busch 2010³⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Carpintero Benítez 1986³⁵	Not in English
Casati 2003³⁶	Not review population
Celidonio 2008³⁷	Unable to obtain
Chen 1998⁴³	Not in English
Chen 2015⁴¹	Not in English
Chen 2015⁴²	Included people having revision joint replacement surgery
Chen 2017³⁹	Not review population
ChiCTR 2017⁴⁴	Conference abstract
Chu 2015⁴⁵	Not review population
Chudinov 1999⁴⁶	Not review population
Dahn 1999⁴⁹	Not in English
Dahn 2003⁴⁸	Not in English
Dauphin 1997⁵⁰	Unclear if the study population is people undergoing primary hip arthroplasty
Davis 1987⁵³	Unclear if the study population is people undergoing primary hip arthroplasty
Davis 1987⁵⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Davis 1989⁵¹	Unclear if the study population is people undergoing primary hip arthroplasty
Davis 1989⁵²	Unclear if the study population is people undergoing primary hip arthroplasty
Demirel 2014⁵⁵	Unclear if the study population is people undergoing primary hip arthroplasty
Deng C 2015⁵⁷	Not in English
Deniz 2014⁵⁸	Unclear if the study population is people undergoing primary hip arthroplasty
Desmet 2017⁵⁹	Unclear if the study population is people undergoing primary hip arthroplasty
Divella 2012⁶⁰	Unclear if the study population is people undergoing primary hip arthroplasty
Drakeford 1991⁶³	Unclear if the study population is people undergoing primary hip arthroplasty
Duarte 2009⁶⁵	Inappropriate comparison
Essving 2011⁶⁷	Unclear if the study population is people undergoing primary arthroplasty
Etches 1995⁶⁸	Inappropriate comparison
Fields 2015⁷⁰	Not review population
Fletcher 1995⁷¹	Inappropriate comparison
Fogarty 1995⁷²	Unclear if the study population is people undergoing primary hip arthroplasty
Forget 2009⁷³	Not in English
Forst 1999⁷⁴	Incorrect interventions
Foss 2005⁷⁵	Not review population
Fouad 2010⁷⁶	Conference abstract
Fournier 1996⁷⁷	Conference abstract
Fournier 1996⁷⁸	Conference abstract
Fournier 1998⁷⁹	Unclear if the study population is people undergoing primary hip arthroplasty
Fournier 2005⁸⁰	Incorrect interventions
Frassanito 2008⁸¹	Inappropriate comparison
Fredin 1986⁸²	Unclear if the study population is people undergoing primary arthroplasty
Fredrickson 2015⁸³	Incorrect interventions
Gasanova 2019⁸⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Gelmanas 2010⁸⁵	Conference abstract
Ghabach 2016⁸⁶	Unclear if the study population is people undergoing primary hip arthroplasty
Ghoneim 1988⁸⁷	Not review population
Gonano 2006⁸⁸	Not review population
Greimel 2017⁹²	Observational study without adjustment for confounding factors
Guay 2014⁹³	Overview of Cochrane reviews
Guay 2017⁹⁴	Systematic review with different inclusion criteria however included studies were checked for this review
Haghighi 2017⁹⁵	Unclear if the study population is people undergoing primary hip arthroplasty
Heidari 2011⁹⁸	Not review population
Helwani 2015⁹⁹	Included people having revision joint replacement surgery
Hemmerling 2010¹⁰⁰	Unclear if the study population is people undergoing primary arthroplasty
Hole 1980¹⁰³	Unclear if the study population is people undergoing primary hip arthroplasty
Hua 2017¹⁰⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Ilango 2016¹⁰⁶	Incorrect study design
Ilfeld 2009¹⁰⁷	Incorrect interventions
Ilfeld 2010¹⁰⁸	Incorrect interventions
Jakobsen 1986¹⁰⁹	Unclear if the study population is people undergoing primary hip arthroplasty
Jia 2017¹¹⁰	Systematic review with different inclusion criteria however included studies were checked for this review
Jimenez-almonte 2016¹¹¹	Systematic review with different inclusion criteria however included studies were checked for this review
Johnson 2016¹¹³	Systematic review with different inclusion criteria however included studies were checked for this review
Johnson 2017¹¹²	Incorrect interventions
Jones 1990¹¹⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Juelsgaard 1998¹¹⁵	Not review population
Jules-elysee 2015¹¹⁶	Inappropriate comparison
Kacha 2018¹¹⁷	Not review population
Kai 2010¹¹⁸	Not in English
Kampe 1999¹²¹	Unclear if the study population is people undergoing primary arthroplasty
Kampe 2001¹²⁰	Unclear if the study population is people undergoing primary arthroplasty
Kampe 2003¹¹⁹	Unclear if the study population is people undergoing primary arthroplasty
Kandler 1993¹²²	Incorrect interventions
Karaaslan 2006¹²³	Not in English
Kaya 2006¹²⁴	Not in English
Kearns 2016¹²⁵	Inappropriate comparison
Kehlet 2015¹²⁶	Literature review
Kendrisic 2017¹²⁷	Unclear if the study population is people undergoing primary hip arthroplasty
Kim 2002¹²⁹	Not in English
Kim 2007¹²⁸	Not in English
Koehler 2017¹³⁰	Incorrect interventions
Koroglu 2008¹³¹	Unclear if the study population is people undergoing primary arthroplasty
Kuchalik 2013¹³³	Not in English
Kuchalik 2017¹³⁵	Inappropriate comparison
Kuchalik 2017¹³⁶	Unclear if the study population is people undergoing primary hip arthroplasty
Lee 2009¹³⁷	Incorrect interventions
Li 2018¹³⁸	Not in English
Liu 2014¹³⁹	Incorrect study design
Loncar Stojiljkovic 2016¹⁴¹	Unclear if the study population is people undergoing primary arthroplasty
Lu 2010¹⁴²	Not in English
Mandal 2011¹⁴⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Marino 2009¹⁴⁵	Inappropriate comparison
Markel 1997¹⁴⁶	Unclear if the study population is people undergoing primary arthroplasty
Marshall 2008¹⁴⁸	Unable to obtain
Martin 2006¹⁴⁹	People undergoing revision surgery included in the study
Maurer 2003¹⁵⁰	Unclear if the study population is people undergoing primary arthroplasty
Mcbeath 1995¹⁵²	Observational study with no adjustment for confounding factors
Mcgraw-tatum 2017¹⁵³	Unclear if the study population is people undergoing primary hip arthroplasty
Mei 2017¹⁵⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Mendieta sánchez 1999¹⁵⁵	Not in English
Messina 2013¹⁵⁶	Not review population
Meuret 2018¹⁵⁷	Not review population
Modig 1976¹⁵⁸	Observational study with no adjustment for confounding factors
Modig 1981¹⁶¹	Unclear if the study population is people undergoing primary hip arthroplasty
Modig 1983¹⁵⁹	Unclear if the study population is people undergoing primary hip arthroplasty
Modig 1983¹⁶⁰	Unclear if the study population is people undergoing primary hip arthroplasty
Mouzopoulos 2009¹⁶³	Not review population
Murphy 1984¹⁶⁴	Inappropriate comparison
Nakai 2013¹⁶⁶	Unclear if the study population is people undergoing primary arthroplasty
Neuman 2016¹⁶⁹	Study protocol
Neuman 2016¹⁷⁰	Unclear if the study population is people undergoing primary hip arthroplasty
Nielsen 2019¹⁷²	Incorrect interventions
Niemi 1993¹⁷⁴	Included people having revision joint replacement surgery
Niemi 1996¹⁷³	Not review population
Nishi 2018¹⁷⁵	Not review population
Nishio 2014¹⁷⁷	Incorrect interventions
Nishio 2017¹⁷⁶	Unclear if the study population is people undergoing primary arthroplasty
Nohel 2011¹⁷⁸	Conference abstract
Onal 2007¹⁷⁹	Not in English
Ozhan 2012¹⁸¹	Not in English
Pandazi 2013¹⁸²	Unclear if the study population is people undergoing primary hip arthroplasty
Park 1994¹⁸³	Not in English
Parker 2015¹⁸⁴	Not review population
Parvataneni 2007¹⁸⁵	Inappropriate comparison
Patorno 2014¹⁸⁶	Not review population
Pavy 2007¹⁸⁷	Not in English
Pedersen 1986¹⁸⁸	Not in English
Perlas 2016¹⁸⁹	Not review population
Racle 1986¹⁹⁰	Not in English
Rashid 2013¹⁹¹	Not review population
Riis 1983¹⁹²	Unclear if the study population is people undergoing primary hip arthroplasty
Rikalainen-salmi 2012¹⁹³	Unclear if the study population is people undergoing primary hip arthroplasty
Saglik 2015¹⁹⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Saksena Shrivastava 2011¹⁹⁵	Conference abstract
Salo 1990¹⁹⁶	Unclear if the study population is people undergoing primary hip arthroplasty
Sansonnens 2016¹⁹⁷	Incorrect study design
Seet 2006¹⁹⁸	Not review population
Shariat 2013¹⁹⁹	Unclear if the study population is people undergoing primary arthroplasty
Shi 2015²⁰⁰	Observational study without adjustment for confounding factors
Siddiqui 2007²⁰¹	Unclear if the study population is people undergoing primary hip arthroplasty
Singelyn 1999²⁰³	Unclear if the study population is people undergoing primary arthroplasty
Singelyn 2005²⁰²	Unclear if the study population is people undergoing primary arthroplasty
Sitsen 2007²⁰⁴	Not review population
Smet 2008²⁰⁵	Not review population
Solovyova 2013²⁰⁶	Unclear if the study population is people undergoing primary arthroplasty
Souron 2003²⁰⁷	Incorrect interventions
Specht 2011²⁰⁸	Inappropriate comparison
Srampickal 2019²⁰⁹	Incorrect interventions
Stevens 2000²¹¹	Unclear if the study population is people undergoing primary hip arthroplasty
Stevens 2007²¹⁰	Unclear if the study population is people undergoing primary arthroplasty
Striebel 1993²¹²	Not in English
Stundner 2012²¹³	Not review population
Sun 2014²¹⁴	Not in English
Surange 2012²¹⁵	Unclear if the study population is people undergoing primary hip arthroplasty
Sveticic 2004²¹⁶	Not review population
Tammachote 2013²¹⁷	Not review population
Tetsunaga 2015²¹⁸	Observational study with no adjustment for confounding factors
Thomas 2009²¹⁹	Conference abstract
Thybo 2016²²⁰	Incorrect interventions
Thybo 2016²²¹	Incorrect interventions
Turker 2003²²³	Unclear if the study population is people undergoing primary arthroplasty
Tzimas 2018²²⁵	Not review population
Uhrbrand 1992²²⁶	Unclear if the study population is people undergoing primary hip arthroplasty
Valentin 1986²²⁷	Unclear if the study population is people undergoing primary hip arthroplasty
Van herreweghe 2015²²⁸	Conference abstract
Vermeylen 2019²²⁹	Not in English
Wang 2006²³¹	Not in English
Wang 2017²³²	Systematic review with different inclusion criteria however included studies were checked for this review
Whiting 2015²³³	Not review population
Wiesmann 2014²³⁴	Unclear if the study population is people undergoing primary hip arthroplasty
Wulf 1999²³⁵	Unclear if the study population is people undergoing primary hip arthroplasty
Yhim 2017²³⁷	Unclear if the study population is people undergoing primary hip arthroplasty
Zorrilla-vaca 2016²³⁹	Systematic review with different inclusion criteria however included studies were checked for this review

Table 29Studies excluded from the health economic review

Reference	Reason for exclusion
None

Evidence review for anaesthesia for hip replacement

Authors

1. Anaesthesia for elective hip joint replacement

1.2. Introduction

1.3. PICO table

1.4. Clinical evidence

1.4.1. Included studies

1.4.2. Excluded studies

1.4.3. Summary of clinical studies included in the evidence review

1.4.4. Quality assessment of clinical studies included in the evidence review

1.5. Economic evidence

1.5.1. Included studies

1.5.2. Excluded studies

1.5.3. Summary of studies included in the economic evidence review

1.5.4. Health economic modelling

1.5.5. Unit costs

1.6. Evidence statements

1.6.1. Clinical evidence statements

1.6.2. Health economic evidence statements

1.7. The committee’s discussion of the evidence

1.7.1. Interpreting the evidence

1.7.1.1. The outcomes that matter most

1.7.1.2. The quality of the evidence

1.7.1.3. Benefits and harms

Comparisons including only regional anaesthesia

Comparisons including only general anaesthesia

Comparisons including both regional and general anaesthesia

1.7.2. Cost effectiveness and resource use

1.7.3. Other factors the committee took into account

References

Appendices

Appendix A. Review protocols

Appendix B. Literature search strategies

B.1. Clinical search literature search strategy

B.2. Health Economics literature search strategy

Appendix C. Clinical evidence selection

Appendix D. Clinical evidence tables

Appendix E. Forest plots

E.1. Regional anaesthesia with nerve block versus regional anaesthesia

E.2. Regional anaesthesia with LIA versus regional anaesthesia with nerve block

E.3. Regional anaesthesia with LIA versus regional anaesthesia

E.4. Regional anaesthesia versus general anaesthesia

E.5. General anaesthesia with LIA versus general anaesthesia with nerve block

E.6. General anaesthesia with LIA versus general anaesthesia

E.7. General anaesthesia with nerve block versus general anaesthesia

Appendix F. GRADE tables

Appendix G. Health economic evidence selection

Appendix H. Health economic evidence tables

Appendix I. Nerve block threshold analysis

I.1. Method

I.2. Results

I.3. Conclusions

Appendix J. Excluded studies

J.1. Excluded clinical studies

J.2. Excluded health economic studies

Table 1PICO characteristics of review question

Table 2Summary of studies included in the evidence review

Table 3RCT evidence summary: regional anaesthesia with nerve block versus regional anaesthesia

Table 4RCT evidence summary: Regional anaesthesia with LIA versus regional anaesthesia with nerve block

Table 5RCT evidence summary: Regional anaesthesia with LIA versus regional anaesthesia

Table 6RCT evidence summary: regional anaesthesia versus general anaesthesia

Table 7Observational studies evidence summary: regional anaesthesia versus general anaesthesia

Table 8RCT evidence summary: General anaesthesia with LIA versus general anaesthesia with nerve block

Table 9RCT evidence summary: General anaesthesia with LIA versus general anaesthesia

Table 10RCT evidence summary: General anaesthesia with nerve block versus general anaesthesia

Table 11Health economic evidence profile: LAI in addition to a standard anaesthetic regimen versus standard anaesthetic regimen only

Table 12Health economic evidence profile: Spinal anaesthesia versus general anaesthesia

Table 13Mean costs of anaesthesia for hip fracture in a UK hospital in 2010

Table 14UK 2018 cost for the addition of a nerve block to an anaesthetic regimen for primary elective joint replacement when varying administration time and the inclusion of theatre time cost

Table 16Health economic review protocol

Table 17Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

Cochrane Library (Wiley) search terms

Epistemonikos search terms

Table 18Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

NHS EED and HTA (CRD) search terms

figure 1Flow chart of clinical study selection for the review of anaesthesia for hip replacement surgery