Evidence review for wound lavage

National Guideline Centre (UK)

Evidence review for wound lavage

Joint replacement (primary): hip, knee and shoulder

Evidence review H

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. Wound lavage

1.1. Review question: In adults having primary elective joint replacement, what is the clinical and cost effectiveness of antibiotic or antiseptic wound lavage during the procedure?

1.2. Introduction

Wound lavage or irrigation is a washout process routinely used during surgery when performing hip, knee and shoulder replacements. It is used to remove contamination and debris from the site of an operation during the procedure. It is seen as a key part of joint replacement surgery.

In so doing this enables:

1): the clinician to have a clear view of the site.

2): the exposure and preparation of bone surfaces - allowing the adhesive cement, used in the procedure, to penetrate the bone enabling a solid and lasting fix (of the implant).

3): the removal of debris that, potentially, might pass into the blood stream and so to another site in the body.

4): a reduction in microbial contamination of the operative site, potentially reducing infection.

The solution used to washout the area of surgery during joint replacement surgery varies; usually influenced by the surgeon’s preference: normal saline, an antiseptic solution or a solution containing antibiotics can be used. However, what is not known is whether the addition of antibiotics and/or antiseptic solutions to the wound lavage fluid help to reduce the risk of infection more effectively than using wound lavage with normal saline solution, alone.

This review focuses on whether antiseptic and/or antibiotic components, when added to the irrigation fluid, are clinically and cost effective when compared to irrigation with saline alone.

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

No relevant clinical studies were identified comparing saline wound lavage with an additional antiseptic and/or antibiotic agent to saline wound lavage without additional agent in adults having primary elective joint replacement. The searches looked for both RCTs and also non-randomised studies.

See also the study selection flow chart in Appendix C:

1.4.2. Excluded studies

See the excluded studies list in Appendix E:

1.5. Economic evidence

1.5.1. Included studies

No relevant health economic studies were identified.

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.

1.5.3. Unit costs

Relevant unit costs are provided below to aid consideration of cost effectiveness.

Table 2

UK costs for irrigation solution composition.

Table 3

UK costs for irrigation delivery method.

1.6. Evidence statements

1.6.1. Clinical evidence statements

No relevant clinical studies were identified.

1.6.2. Health economic evidence statements

No relevant economic evaluations were identified.

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 were agreed to be mortality at 30 days, quality of life (QOL), and superficial and deep surgical site infection. Ultimately this review sought to discover whether wound lavage with antiseptic or antibiotics reduces infections (superficial and deep surgical site) and therefore these were the critical outcomes. Mortality at 30 days and quality of life (QOL) considered were surrogates for infection.

The important outcomes were return to theatre, allergic reaction, adverse antibiotic reactions, hospital readmission, pain and length of stay.

1.7.1.2. The quality of the evidence

No clinical studies relevant to the review question were identified.

1.7.1.3. Benefits and harms

Infections after joint replacement surgery are rare, but when they occur, the cost to the person can be very high, and the financial cost to the NHS is significant. Surgical site infection can lead to catastrophic outcomes, in extreme cases it can result in systemic infection and sepsis resulting in death or it can lead to severe local infection that may necessitate amputation of the affected limb.

The committee discussed how wound lavage/irrigation might reduce surgical site infection. It is thought that a vector of infection is bacteria settling on the wound during surgery and that irrigation of the wound might remove these bacteria and consequently reduces infections. The addition of antibiotics or antiseptics to the irrigation solution has been postulated to increase the anti-infection effect.

The committee accepted that no evidence was found for this evidence review and there was no consensus amongst the committee that the addition of antibiotics or antiseptics to irrigation solution reduces infections. The committee were also concerned this uncertainly of effectiveness would be combined with the potential negative effect of the agents leading to increase antimicrobial resistance.

The committee discussed that would lavage is also used to remove debris generated during the preparation of the joint surfaces for surgery. This enables the surgeon to properly see the operative field and accurately undertake the surgery. For cemented implants, as well as preparing the joint surfaces for cementation it helps reduce the risk of cement embolisation syndrome. Thus, irrigation is an established practice that is currently used for more purposes than reduction of surgical site infections.

The committee were aware of the wound irrigation and intracavity lavage recommendations in Surgical site infections: prevention and treatment NICE guideline (NG125).²⁵ The guideline recommends not using wound irrigation or intracavity lavage to reduce the risk of surgical site infection. The committee agreed that current practice for prevention infection includes giving all people having joint replacement surgery prophylactic antibiotics and doing the surgery in ultra clean-air theatres. With this in mind and because of the lack of evidence the committee agreed to recommend not using antibiotic or antiseptic agents in wound lavage for elective joint replacement.

1.7.2. Cost effectiveness and resource use

No economic evaluations were found that matched the protocol. It was discussed that the use of wound lavage is an established part of current practice in joint replacement. The committee noted that saline solution is also used as an irrigation fluid for purposes other than reducing surgical site infection (SSI). Therefore, its use for reducing SSI does not represent an additional cost to a joint replacement operation.

The addition of antiseptics or antibiotics to the wound lavage would represent an additional cost to wound lavage given that their unit costs are greater. However, the additional cost could be unnecessary given that there was no evidence that the addition of antiseptics or antibiotics reduced SSI.

The committee decided to cross refer to the NICE guideline NG125 on SSI, which is not expected to have a resource impact.

1.7.3. Other factors the committee took into account

It was acknowledged during the discussions that there would be economic considerations for the methods of lavage. For example, pulsed lavage may cost significantly more than using a jug or syringe due to the equipment and batteries required. However, there was no comparison of the methods of lavage in this evidence review; therefore, no recommendations have been made on this.

NJR data would have been used had the data been analysed and adjusted for confounding factors. No such data were identified.

References

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17.: Kok EHAT, Rhijn LW, Rietra PJGM. The effect of wound irrigation on bacterial comtamination of suction instrumentation during joint prosthesis surgery. Nederlands tijdschrift voor orhopaedie. 1998; 5(1):22

18.: Lin D, Burke C, Jia N, Zuckerman J, Ciavarra G. Diagnostic utility of lavage for periprosthetic joint infection: Are the culture results reliable? Skeletal Radiology. 2018; 47 (3):443

19.: Lortat-Jacob A. Antibiotic prophylaxis in orthopedic surgery. Annales Françaises d’Anesthésie et de Réanimation. 1994; 13:(Suppl 1):S51–60 [PubMed: 7778813]

20.: Memon M, Kay J, Gholami A, Simunovic N, Ayeni OR. Fluid extravasation in shoulder arthroscopic surgery: A systematic review. Orthopaedic Journal of Sports Medicine. 2018; 6(5) [PMC free article: PMC5954585] [PubMed: 29785406]

21.: Mont MA, Waldman BJ, Hungerford DS. Evaluation of preoperative cultures before second-stage reimplantation of a total knee prosthesis complicated by infection. A comparison-group study. Journal of Bone and Joint Surgery (American Volume). 2000; 82-A(11):1552–7 [PubMed: 11097443]

22.: Mortada M, Elewa EA. Knee lavage versus intra articular hyaluronan in advanced knee osteoarthritis. Annals of the Rheumatic Disease Conference: Annual European Congress of Rheumatology of the European League Against Rheumatism, EULAR. 2012; 71(Suppl 3)

23.: Moseley JB, Wray NP, Kuykendall D, Willis K, Landon G. Arthroscopic treatment of osteoarthritis of the knee: A prospective, randomized, placebo-controlled trial. Results of a pilot study. American Journal of Sports Medicine. 1996; 24(1):28–34 [PubMed: 8638750]

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25.: National Institute for Health and Care Excellence. Surgical site infections: prevention and treatment. NICE guideline 125. London. National Institute for Health and Care Excellence, 2019. Available from: https://www.nice.org.uk/guidance/ng125

26.: NHS Supply Chain Catalogue. NHS Supply Chain, 2018. Available from: http://www.supplychain.nhs.uk/

27.: Norman G, Atkinson RA, Smith TA, Rowlands C, Rithalia AD, Crosbie EJ et al. Intracavity lavage and wound irrigation for prevention of surgical site infection. Cochrane Database of Systematic Reviews 2017, Issue 10. Art. No.: CD012234. DOI: 10.1002/14651858.CD012234.pub2. [PMC free article: PMC5686649] [PubMed: 29083473] [CrossRef]

28.: Riesgo AM, Park BK, Herrero CP, Yu S, Schwarzkopf R, Iorio R. Vancomycin povidone-iodine protocol improves survivorship of periprosthetic joint infection treated with irrigation and debridement. Journal of Arthroplasty. 2018; 33(3):847–850 [PubMed: 29174761]

29.: Shah NB, Hersh BL, Kreger AM, Sayeed A, Bullock AG, Rothenberger SD et al. Benefits and Adverse Events Associated with Extended Antibiotic Use in Total Knee Arthroplasty Periprosthetic Joint Infection. Clinical Infectious Diseases. 2019; 04:04 [PMC free article: PMC7768747] [PubMed: 30944931]

30.: Sneath RJ, Bindi FD, Davies J, Parnell EJ. The effect of pulsed irrigation on the incidence of heterotopic ossification after total hip arthroplasty. Journal of Arthroplasty. 2001; 16(5):547–551 [PubMed: 11503112]

31.: Sultan AA, Samuel LT, Umpierrez E, Swiergosz A, Rabin J, Mahmood B et al. Routine use of commercial antibiotic-loaded bone cement in primary total joint arthroplasty: A critical analysis of the current evidence. Annals of Translational Medicine. 2019; 7(4):73 [PMC free article: PMC6409235] [PubMed: 30963068]

32.: Teeny SM, Dorr L, Murata G, Conaty P. Treatment of infected total knee arthroplasty. Irrigation and debridement versus two-stage reimplantation. Journal of Arthroplasty. 1990; 5(1):35–9 [PubMed: 2319246]

33.: Timperley AJ, Whitehouse SL. Mitigating surgical risk in patients undergoing hip arthroplasty for fractures of the proximal femur. Journal of Bone and Joint Surgery - Series B. 2009; 91(7):851–854 [PubMed: 19567845]

34.: Triantafyllopoulos GK, Poultsides LA, Zhang W, Sculco PK, Ma Y, Sculco TP. Periprosthetic knee infections treated with irrigation and debridement: Outcomes and preoperative predictive factors. Journal of Arthroplasty. 2015; 30(4):649–657 [PubMed: 25466169]

35.: Turhan S. Does the use of antibiotic-loaded bone cement have an effect on deep infection in primary total knee arthroplasty practice? Surgical Infections. 2019; 20(3):244–246 [PubMed: 30707653]

36.: Weenders SGM, Nijhof MW, Schimmel JJP, Goosen JHM. Debridement, antibiotics and implant retention in early periprosthetic joint infection after primary total hip arthroplasty: 88 percent survival after two years follow-up. Acta Orthopaedica Belgica. 2016; 82(3):530–538 [PubMed: 29119894]

37.: Wintzell G, Haglund-Akerlind Y, Nowak J, Larsson S. Arthroscopic lavage compared with nonoperative treatment for traumatic primary anterior shoulder dislocation: A 2-year follow-up of a prospective randomized study. Journal of Shoulder and Elbow Surgery. 1999; 8(5):399–402 [PubMed: 10543589]

38.: Wong J, Abrishami A, De Silva Y, Hasan SM, Mahomed N, Chung F. A randomized controlled trial of topical tranexamic acid for postoperative blood loss in total knee arthroplasty. Anesthesia and Analgesia. 2009; 108:S–22

39.: Yazdi H, Moradi A, Herbort M. The effect of gentamicin in irrigating solutions on articular infection prophylaxis during arthroscopic ACL reconstruction. Archives of Orthopaedic and Trauma Surgery. 2014; 134(2):257–261 [PubMed: 24323062]

40.: Zhao J, Zhang J, Ji X, Li X, Qian Q, Xu Q. Does intramedullary canal irrigation reduce fat emboli? A randomized clinical trial with transesophageal echocardiography. Journal of Arthroplasty. 2015; 30(3):451–455 [PubMed: 25458091]

Appendices

Appendix A. Review protocols

Table 4. Review protocol: Wound lavage (PDF, 214K)

Table 5. 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.²⁴

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 6. Database date parameters and filters used

Medline (Ovid) search terms

Embase (Ovid) search terms

Cochrane Library (Wiley) 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 7. 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 wound lavage

Appendix D. Health economic evidence selection

Figure 2. Flow chart of health economic study selection for the guideline

Appendix E. Excluded studies

E.1. Excluded clinical studies

Table 8. Studies excluded from the clinical review

Final

Intervention evidence review underpinning recommendation 1.5.1 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: NBK561387PMID: 32881454

Table 1PICO characteristics of review question

Population	Adults having primary elective joint replacement.
Interventions	Wound lavage with saline and antiseptic agent(s) Wound lavage with saline and antibiotic agent(s) Wound lavage with saline and antiseptic and antibiotic agents
Comparisons	Wound lavage with saline
Outcomes	Critical Mortality at 30 days Quality of life Superficial Surgical site infection Deep surgical site infection Important Return to theatre Allergic reaction Adverse antibiotic reactions Hospital readmission Pain Length of stay
Study design	Randomised controlled trials If no well-conducted RCTs are available, then observational studies with multivariate analysis will be investigated.

Table 2UK costs for irrigation solution composition

Active Ingredient	Size	Unit Cost	Cost (per litre)
Sodium chloride 9 mg per 1 ml^(a)	1000ml	£1.09	£1.09
Chlorhexidine gluconate 5 mg per 1 ml	600ml	£4.72	£7.87
Chlorhexidine gluconate 40 mg per 1 ml	500ml	£5.25	£10.50
Povidone-Iodine 75 mg per 1 ml	500ml	£7.67	£15.34
Vancomycin (as Vancomycin hydrochloride)	500mg	£6.25	£13.59^(b)

: Source: Joint Formulary Committee¹⁵

(a): Costs only available for 1L bags when 3L more commonly used

(b): When used as a concentration of 1g/L, cost includes 1L saline solution as listed above

Table 3UK costs for irrigation delivery method

Site of surgery	Brand	Model description	Unit Cost
Hip or Knee	Fannin	Clean disposable pulse lavage system	£21.03
	Tava	Single use pulse lavage system	£21.65
	Morgan Steer	Microaire fan kit including fully-disposable pulse lavage component kit and fan spray tip with splash shield	£34.77
	Ortho Dynamics	Knee or hip kit including fully disposable pulse lavage component kit and shower spray tip with splash shield	£38.40
	MDM Medical ltd	Single use pulse lavage system with knee tip only	£48.87
	No brand listed	Eco hip arthroplasty brush pump lavage kit with suction 702	£50.54
Shoulder	Rocialle	Sterile 1 litre jug	£0.49
Shoulder	BD Plastipak	50ml catheter syringe	£0.35

: Source: NHS Supply Catalogue 2018²⁶

Table 5Health 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).²⁴ 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 6Database 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

DARE, and NHSEED to 2015 Issue 2 of 4

HTA to 2016 Issue 4 of 4

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.	Therapeutic Irrigation/
26.	(irrigat* or lavage or douch*).ti,ab.
27.	(wound* adj5 (clean* or decontaminat* or soak* or rins* or wash*)).ti,ab.
28.	(water or H2O or saline or solution* or soap* or detergent*).ti,ab.
29.	((Intraoperative or intra-operative or operative or surg) adj3 (clean or decontaminat* or soak* or rins* or wash*)).ti,ab.
30.	((medicat* or pump* or power-puls* or puls* or power assist* or assist* or pressure* or manual) adj3 (wash* or clean*)).ti,ab.
31.	Saline Solution, Hypertonic/
32.	Detergents/
33.	Soaps/
34.	Water/
35.	Solutions/
36.	or/25-35
37.	Anti-bacterial agents/
38.	Cephalosporins/
39.	Vancomycin/
40.	Gentamicins/
41.	Bacitracin/
42.	(antibiotic* or anti-biotic* or antibacteri* or anti-bacteri* or cephalosporin* or vancomycin or gentamicin* or bacitracin).ti,ab.
43.	or/37-42
44.	Anti-Infective Agents, Local/
45.	Chlorhexidine/
46.	Hydrogen Peroxide/
47.	Povidone-Iodine/
48.	Iodine/
49.	Hypochlorous Acid/
50.	(antiseptic* or antimicrobi* or anti-microbi* or anti-infecti* or antiinfective or chlorhexidine* or peroxide* or povidone* or iodine or betadine or hypochlor*).ti,ab.
51.	or/44-50
52.	24 and (36 or 43 or 51)
53.	randomized controlled trial.pt.
54.	controlled clinical trial.pt.
55.	randomi#ed.ti,ab.
56.	placebo.ab.
57.	randomly.ti,ab.
58.	Clinical Trials as topic.sh.
59.	trial.ti.
60.	or/53-59
61.	Meta-Analysis/
62.	exp Meta-Analysis as Topic/
63.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
64.	((systematic* or evidence) adj3 (review or overview*)).ti,ab.
65.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
66.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
67.	(search* adj4 literature).ab.
68.	(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.
69.	cochrane.jw.
70.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
71.	or/61-70
72.	Epidemiologic studies/
73.	Observational study/
74.	exp Cohort studies/
75.	(cohort adj (study or studies or analys* or data)).ti,ab.
76.	((follow up or observational or uncontrolled or non randomi#ed or epidemiologic*) adj (study or studies or data)).ti,ab.
77.	((longitudinal or retrospective or prospective or cross sectional) and (study or studies or review or analys* or cohort* or data)).ti,ab.
78.	Controlled Before-After Studies/
79.	Historically Controlled Study/
80.	Interrupted Time Series Analysis/
81.	(before adj2 after adj2 (study or studies or data)).ti,ab.
82.	or/73-82
83.	exp case control study/
84.	case control*.ti,ab.
85.	or/84-85
86.	83 or 86
87.	Cross-sectional studies/
88.	(cross sectional and (study or studies or review or analys* or cohort* or data)).ti,ab.
89.	or/88-89
90.	83 or 90
91.	83 or 86 or 90
92.	52 and (60 or 71 or 91)

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.	lavage/
24.	(irrigat* or lavage or douch*).ti,ab.
25.	(wound* adj5 (clean* or decontaminat* or soak* or rins* or wash*)).ti,ab.
26.	(water or H2O or saline or solution* or soap* or detergent*).ti,ab.
27.	((Intraoperative or intra-operative or operative or surg) adj3 (clean or decontaminat* or soak* or rins* or wash*)).ti,ab.
28.	((medicat* or pump* or power-puls* or puls* or power assist* or assist* or pressure* or manual) adj3 (wash* or clean*)).ti,ab.
29.	hypertonic solution/
30.	detergent/
31.	soap/
32.	water/
33.	"solution and solubility"/
34.	or/23-33
35.	antibiotic agent/
36.	cephalosporin derivative/
37.	vancomycin/
38.	gentamicin/
39.	bacitracin/
40.	(antibiotic* or anti-biotic* or antibacteri* or anti-bacteri* or cephalosporin* or vancomycin or gentamicin* or bacitracin).ti,ab.
41.	or/35-40
42.	antiinfective agent/
43.	chlorhexidine/
44.	hydrogen peroxide/
45.	povidone iodine/
46.	iodine/
47.	hypochlorous acid/
48.	(antiseptic* or antimicrobi* or anti-microbi* or anti-infecti* or antiinfective or chlorhexidine* or peroxide* or povidone* or iodine or betadine or hypochlor*).ti,ab.
49.	or/42-48
50.	22 and (34 or 41 or 49)
51.	random*.ti,ab.
52.	factorial*.ti,ab.
53.	(crossover* or cross over*).ti,ab.
54.	((doubl* or singl) adj blind).ti,ab.
55.	(assign* or allocat* or volunteer* or placebo*).ti,ab.
56.	crossover procedure/
57.	single blind procedure/
58.	randomized controlled trial/
59.	double blind procedure/
60.	or/51-59
61.	systematic review/
62.	meta-analysis/
63.	(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.
64.	((systematic* or evidence) adj3 (review or overview*)).ti,ab.
65.	(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
66.	(search strategy or search criteria or systematic search or study selection or data extraction).ab.
67.	(search* adj4 literature).ab.
68.	(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.
69.	cochrane.jw.
70.	((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.
71.	or/61-70
72.	Clinical study/
73.	Observational study/
74.	family study/
75.	longitudinal study/
76.	retrospective study/
77.	prospective study/
78.	cohort analysis/
79.	follow-up/
80.	cohort*.ti,ab.
81.	80 and 81
82.	(cohort adj (study or studies or analys* or data)).ti,ab.
83.	((follow up or observational or uncontrolled or non randomi#ed or epidemiologic*) adj (study or studies or data)).ti,ab.
84.	((longitudinal or retrospective or prospective or cross sectional) and (study or studies or review or analys* or cohort* or data)).ti,ab.
85.	(before adj2 after adj2 (study or studies or data)).ti,ab.
86.	or/73-79,82-86
87.	exp case control study/
88.	case control*.ti,ab.
89.	or/88-89
90.	or 90
91.	cross-sectional study/
92.	(cross sectional and (study or studies or review or analys* or cohort* or data)).ti,ab.
93.	or/92-93
94.	or 94
95.	or 90 or 94
96.	and (60 or 71 or 95)

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: [Therapeutic Irrigation] this term only
#16.	(irrigat* or lavage or douch*):ti,ab
#17.	(wound* near/5 (clean* or decontaminat* or soak* or rins* or wash*)):ti,ab
#18.	(water or H2O or saline or solution* or soap* or detergent*):ti,ab
#19.	((Intraoperative or intra-operative or operative or surg) near/3 (clean or decontaminat* or soak* or rins* or wash*)):ti,ab
#20.	((medicat* or pump* or power-puls* or puls* or power assist* or assist* or pressure* or manual) near/3 (wash* or clean*)):ti,ab
#21.	MeSH descriptor: [Saline Solution, Hypertonic] this term only
#22.	MeSH descriptor: [Detergents] this term only
#23.	MeSH descriptor: [Soaps] this term only
#24.	MeSH descriptor: [Water] this term only
#25.	MeSH descriptor: [Solutions] this term only
#26.	(or #15-#25)
#27.	MeSH descriptor: [Anti-Bacterial Agents] this term only
#28.	MeSH descriptor: [Cephalosporins] this term only
#29.	MeSH descriptor: [Vancomycin] this term only
#30.	MeSH descriptor: [Gentamicins] this term only
#31.	MeSH descriptor: [Bacitracin] this term only
#32.	(antibiotic* or anti-biotic* or antibacteri* or anti-bacteri* or cephalosporin* or vancomycin or gentamicin* or bacitracin):ti,ab
#33.	(or #27-#32)
#34.	MeSH descriptor: [Anti-Infective Agents, Local] this term only
#35.	MeSH descriptor: [Chlorhexidine] this term only
#36.	MeSH descriptor: [Hydrogen Peroxide] this term only
#37.	MeSH descriptor: [Povidone-Iodine] this term only
#38.	MeSH descriptor: [Iodine] this term only
#39.	MeSH descriptor: [Hypochlorous Acid] this term only
#40.	(antiseptic* or antimicrobi* or anti-microbi* or anti-infecti* or antiinfective or chlorhexidine* or peroxide* or povidone* or iodine or betadine or hypochlor*):ti,ab
#41.	(or #34-#40)
#42.	#14 and (or #26, #33, #41)

Table 7Database 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 wound lavage

Figure 2Flow 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 8Studies excluded from the clinical review

Study	Exclusion reason
Abdelaziz 2019¹	Incorrect interventions
Abdeldayem 2018²	Inappropriate comparison
Anglen 2005³	Incorrect population
Anon 2001⁴	Literature review
Capito 2017⁵	Incorrect interventions. Not review population
Chung 2019⁶	Incorrect interventions
Cobden 2019⁷	Incorrect study design
Cohen 2019⁸	Observational study not suitably adjusted for confounders
Ennin 2012⁹	Incorrect study design. Not review population
Fei 2011¹⁰	Inappropriate comparison
Fernicola 2019¹¹	Systematic review: included studies checked for this review
Frisch 2017¹²	Observational study: no adjustment for confounding factors
Gupta 2016¹³	Incorrect interventions
Heckmann 2019¹⁴	Systematic review: included studies checked for this review
Kantak 2017¹⁶	Inappropriate comparison
Kok 1998¹⁷	Unavailable
Lin 2018¹⁸	Unavailable
Lortat-jacob 1994¹⁹	Not in English
Memon 2018²⁰	Incorrect interventions
Mont 2000²¹	Incorrect interventions
Mortada 2012²²	Unavailable
Moseley 1996²³	Incorrect population
Norman 2017²⁷	Incorrect population
Riesgo 2018²⁸	Incorrect population
Shah 2019²⁹	Inappropriate comparison
Sneath 2001³⁰	Incorrect interventions
Sultan 2019³¹	Systematic review: included studies checked for this review
Teeny 1990³²	Not review population
Timperley 2009³³	Incorrect study design
Triantafyllopoulos 2015³⁴	Incorrect interventions
Turhan 2019³⁵	Incorrect interventions
Weenders 2016³⁶	Incorrect interventions
Wintzell 1999³⁷	Not review population. Inappropriate comparison
Wong 2009³⁸	Incorrect population
Yazdi 2014³⁹	Incorrect population
Zhao 2015⁴⁰	Inappropriate comparison