Question

What is the role of antibiotic-impregnated bone cement?

Recommendation

When inserting a primary cemented hip prosthesis, always use an antibiotic-impregnated cement (in combination with systemic antibiotic prophylaxis).

Introduction

If bone cement is used in total joint arthroplasty, in the Netherlands the advice is to use antibiotic-loaded cement as standard of care. This facilitates the local release of antibiotics, leading to a higher local concentration, with the aim to reduce the rate of deep infection Wang, (2013). The type of antibiotic used in bone cement should be effective against the main bacterial causes of deep infection.

Conclusions

Risk of superficial infection

High

GRADE

Antibiotic-impregnated bone cement did not decrease the rate of superficial infection compared to plain bone cement in patients undergoing hip or knee arthroplasty.

 

Sources Wang, (2012)

 

Risk of deep infection

High

GRADE

Antibiotic-impregnated bone cement leads to fewer deep wound infections than non-antibiotic-impregnated bone cement in patients undergoing hip or knee arthroplasty.

 

Sources (Parvizi, 2008; Wang, 2012)

 

Revision risk

Low

GRADE

Revision risk seems to be lower for antibiotic-impregnated bone cement compared to non-antibiotic-impregnated bone cement in patients undergoing total hip arthroplasty.

 

Sources (Engesaeter, 2003; Colas, 2015)

Literature summary

Three new studies were included to answer this question, two meta-analyses and a cohort study (Parvizi, 2008; Wang, 2012; Colas, 2015). Also a registry study included in the 2010 guideline was added to the literature summary Engesaeter, (2003).

 

The meta-analysis by Parvizi (2008) included six RCTs (Lynch, 1987, Josefsson, 1990, Josefsson and Kolmert, 1993; Havelin, 1995; Espehaug, 1997), comprising 24,661 THAs (primary and revision hip arthroplasty) comparing antibiotic impregnated cement (gentamicin) with non-antibiotic impregnated cement. Data with regard to the use of systemic antibiotics prophylaxis was limited. Outcomes required for inclusion in the meta-analysis were the incidence of deep infection and the overall survival rate at the specified interval after surgery Parvizi, (2008).

 

The meta-analysis by Wang (2013) included eight RCTs (Pfarr, 1979; Wannske, 1979; Josefsson, 1981; Bohm, 2012; Chiu, 2000; Hinarejos, 2013; McQueen, 1987; McQueen, 1990), regarding patients undergoing primary total hip arthroplasty (Pfarr, 1979; Wannske, 1979; Josefsson, 1981; Bohm, 2012) or total knee arthroplasty (Chiu, 2000; Hinarejos, 2013;), or both (McQueen, 1987; McQueen, 1990). All these studies included an antibiotic-impregnated bone cement trial group and a control group that involved the use of plain bone cement or systemic antibiotics prophylaxis. Outcomes reported were superficial and deep wound infection Wang, (2013).

 

The cohort study of Colas (2015) included 107,382 patients that had undergone a THA for rheumatoid arthritis. It compared revision risk between implants with antibiotic-impregnated cement (21.4%), and either uncemented (74.8%), or antibiotic free cemented implants (3.8%). Median follow-up was 33 months Colas, (2015). The outcome reported was revision risk Colas, (2015).

 

The registry study of Engesaeter (2003; included in the 2010 guideline) included 22,170 THAs. Patients had received systemic antibiotic prophylaxis with a cephalosporin or a penicillin combined with antibiotic impregnated bone cement in 71% of the cases. These patients were compared with those who had received only systemic antibiotics (27%). Main outcome reported was revision risk Engesaeter, (2003).

 

Results

Risk of superficial infection

In the study by Wang (2013) no statistically significant difference was found in risk of superficial infection between antibiotic impregnated cement compared to plain bone cement (RR = 1.42; 95% CI 0.81 to 2.50; P= 0.22).

 

Risk of deep infection

Parvizi (2008) found a weighted mean effect of 0.506 (95% CI (0.341 to 0.751)), p=0.001 for antibiotic cement in reducing the risk of infection in primary THA.

 

Meta-analysis of the cumulative data from all studies confirmed the efficacy of antibiotic cement in reducing the rate of deep infection in primary THA from 2.3% when no antibiotic was present in the cement to 1.2% with the use of antibiotic cement Parvizi, (2008).

 

Wang (2013) found a Risk Ratio of 0.34 (95%CI (0.07; 1.58)) for antibiotic cement for deep infection compared to plain bone cement in both hip and knee surgery. A risk ratio of 0.37 (95% CI (0.14 to 0.98)) was found for antibiotic cement for deep infection compared to systemic antibiotics in both hip and knee surgery. In the subgroup of patients undergoing hip arthroplasty, the risk ratio for a deep infection was 0.21 (95%CI (0.08; 0.5)) for antibiotic cement compared to plain cement Wang, (2013).

 

Revision risk

Colas (2015) showed that antibiotic-impregnated cemented total hip arthroplasties had a better prognosis than uncemented total hip arthroplasties: cumulative revision rates were 2.4% and 3.3%, respectively (P<0.001) and the multivariate adjusted hazard ratio was 0.74 (95%CI, 0.67 to 0.84; P<0.001) Colas, (2015).

 

The registry study by Engesaeter (2003) found that revision risk was 1.4 times higher for those who received antibiotics only systemically, as compared to a combined strategy of systemic antibiotics and impregnated bone cement (P<0.001).

 

Grading of evidence

Risk of superficial infection

For this analysis a meta-analysis of five RCTs was used, the level of evidence was considered high quality.

 

Risk of deep infection

Infection results are based on two meta-analysis of RCTs. Results pointed in the same direction, the level of evidence was not decreased and considered high quality.

 

Revision risk

Revision risk was studied in a cohort study and a registry, the level of evidence was considered low quality.

Search and select

To answer the question a systematic literature analysis was performed for the following research question:

What are the effects of antibiotic containing bone cement, compared to bone cement without antibiotics, in primary total hip arthroplasty for arthrosis or avascular necrosis?

P: primary total hip arthroplasty for arthrosis or avascular necrosis;

I: antibiotic containing bone cement;

C: bone cement without antibiotics;

O: superficial wound infection, deep wound infection, revision risk.

 

Relevant outcome measures

The working group decided that deep wound infection were critical outcome measures for decision making, and regarded superficial wound infection and revision risk as important outcome measures. Any significant difference in infection risk is considered clinically relevant.

 

Search and select (Method)

A literature search was performed with relevant search terms on December 15 2016 in the databases Medline (via OVID) and Embase (via Embase.com). The search strategy is provided in the tab ”Methods”. The literature search resulted in 221 hits. Studies were selected using the following selection criteria: addressing the research question, methodological quality, randomised controlled trial, systematic review, meta-analysis, or registry study. Based on title and abstract 16 studies were preselected. After obtaining full text, thirteen studies were excluded (see exclusion table) and three studies were included in literature analysis (Parvizi, 2008; Wang, 2013; Colas, 2015). Also a registry study included in the 2010 guideline was added to the literature summary Engesaeter, (2003).

 

The most important study characteristics are described in evidence tables. The assessment of risk of bias is provided in risk of bias tables.

References

  1. Colas S, Collin C, Piriou P, et al. Association Between Total Hip Replacement Characteristics and 3-Year Prosthetic Survivorship: A Population-Based Study. JAMA Surg. 2015;150(10):979-88.
  2. Engesæter L, Lie SA, Espehaug B, et al. Antibiotic prophylaxis in total hip arthroplasty: Effects of antibiotic prophylaxis systemically and in bone cement on the revision rate of 22,170 primary hip replacements followed 0 to 14 years in the Norwegian Arthroplasty Register, Acta Orthopaedica Scandinavica, 2003;74:6, 644-651.
  3. Parvizi J, Saleh KJ, Ragland PS, et al. Efficacy of antibiotic-impregnated cement in total hip replacement. A meta-analysis. Acta Orthopaedica, 2008;79(3):335-341.
  4. Wang J, Zhu C, Cheng T, et al. A systematic review and meta-analysis of antibiotic-impregnated bone cement use in primary total hip or knee arthroplasty. PLoS ONE. 2013;8(12):e82745.

Evidence tables

Evidence-table for systematic review of RCTs

Research question: Does antibiotic bone cement reduce deep infection compared to non-antibiotic containing bone cement?

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Parvizi, 2008

SR and meta-analysis of 6 RCTs

 

Literature search up to December 2004

 

A: Espehaug, 1997; Norway; supported by grants from the Norwegian Research Council and the Norwegian Medical Association’s Fund for Quality Improvement

B: Josefsson, 1990; Sweden, unknown

C: Josefsson and Kolmert, 1993; Sweden, unknown

D: Havelin et al., 1995, Norway, unknown

E: Lynch, 1987, England, unknown

F: McQueen, 1987

 

 

Setting and Country: USA

 

Source of funding:

unknown

 

Inclusion criteria SR: primary and revision hip arthroplasty, comparative trials of antibiotic loaded versus non-antibiotic cement, if they included data on 100 or more primary hip replacements or 20 or more revision hip replacements, and if they included outcome data at specified follow-up times. Outcome data required for inclusion were the incidence of deep infection and the overall survival rate at the specified interval after surgery.

 

Exclusion criteria SR: Studies that related to mechanical properties of cement, in vitro studies, and studies of joints other than the hip were excluded; non-clinical studies and non-outcome clinical studies, historical reports and studies without a control group; hips that had been inserted with low-viscosity “Boneloc” cements in the study by Havelin et al. (1995) were excluded; hips in the study by Espehaug et al. (1997) that had been performed using Simplex cement containing erythromycin and colistin were also excluded

 

N=24.661 hip-replacements

 

N=21.445 analysed

Describe intervention:

 

Antibiotic impregnated cement (gentamicin)

 

A: 1) patients receiving antibiotic prophylaxis both systemically and locally in the bone cement (combined regime);

3) those receiving antibiotics in the cement only (cement only regime)

B: gentamicin bone cement (GBC)

C: gentamicin bone cement (GBC)

D: antibiotic cement

E: gentamicin-containing acrylic cement

F: cefuroxime in bone cement

Describe control:

 

Non-antibiotic impregnated cement

 

A: Espehaug, 1997

2) those receiving antibiotics systemically only (systemic only regime);

4) those receiving no antibiotic prophylaxis (no antibiotic

regime).

B: systemic antibiotics

C: systemic antibiotics

D: cement without antibiotics

E: plain bone cement (CMW)

F: systemic cefuroxime

 

End-point of follow-up (minimum follow-up of two years):

 

A: five years

B: five years

C: ten years

D: 3,2 years (range 0 to 6,4)

E: 8,1 for CMW series and 3,6 for Palacos with gentamicin

F: McQueen, 1987

G:

H:

I:

….

 

 

For how many participants were no complete outcome data available?

1,081 hips (4.4%) were lost to

follow-up or the patients died and were excluded

 

 

Outcome measure-1 Deep wound infection

 

Pooled effect (random effects model):

RR 0,51 (95%BI 0,34 to 0,75) favoring antibiotic cement

 

Outcome measure-2 overall survival of the hip prothesis

RR 0,72 (95%BI 0,63 to 0,83) favoring antibiotic cement

 

 

Wang, 2012

SR and meta-analysis of RCTs

Literature search up to june 2013

 

B: Chiu, 2002 Knee

C: Hinarejos, 2013 Knee

D: Josefsson, 1981

E: McQueen, 1987 Hip and knee

F: McQueen, 1990 Hip and knee

G: Pfarr, 1979

H:Wannske, 1979

 

Study design: All RCTs

 

Setting and Country:

B: Taiwan, hospital

C: Spain, hospital

D: Sweden, hospital

E: Scotland, hospital

F: Scotland, hospital

G: Germany, hospital

H:

 

Inclusion criteria SR: patients undergoing a primary THA or TKA; include an AIBC trial group and a control group that involved the use of plain bone cement (PBC) or systemic antibiotic (SA), irrespective of the dose and route of administration; and be a published RCT

 

Exclusion criteria SR: (1) the outcomes were not reported for antibiotic cement use in primary total hip or knee replacement; (2) it was impossible to extrapolate or calculate the necessary data from the published results; (3) primary study patients had a poor physical condition, such as diabetes, malign nt tumor; and (4) studies were animal experiments, in vitro trials or revision arthroplasty, and the operated joint was not the hip or knee

 

8 studies included

 

 

Important patient characteristics at baseline:

 

N, mean age

A: N= 23 (25 hips, 73 yrs

B: N=340, 69 yrs

C: N=2948, 75 yrs

D: N=1633, 69 yrs

E: 295, 68 yrs

F: N=401, 67 yrs

G: N=200, 65 yrs

H: N=476, 64 yrs

Describe intervention:

 

B: 2g cefuroxiume

C: 0,5 g ERY and colistin

D: 0,5 g gentamicin

E: 1,5 g cefuroxime

F: 1,5 g cefuroxime

G: gentamicin

H: gentamicin

 

 

Describe control:

 

B: Simplex P

C: Simplex P

D: Palacos

E: CMV

F: CMV

G: Palacos

H: Palacos

 

 

End-point of follow-up:

 

B: 49 months

C: 12 months

D: 24 months

E: 3 months

F: 24 months

G: 24 months

H: 29 months

 

For how many participants were no complete outcome data available?

(intervention/control)

A: 5 due to missed examinations and further dropout

B: N

C: yes 52

D: yes 52

E: yes

F: yes 4

G: no

H: no

 

Outcome measure-1 infection

Defined as

 

We included the seven RCTs which involved the postoperative infection rate of patient as the data of the metaanalysis in Table S3 in File S1. In the aspect of superficial infection rate, because no significant heterogeneity was observed among the subgroups (P= 0.79; I2= 0%), a fixedeffect model was employed. The overall pooled results of 5 RCTs revealed a significant difference between AIBC and control group (RRs, 1.47; 95% CIs, 1.13 to 1.91; P= 0.004) (Figure 2). Furthermore, we found different results based on the respective analysis of two subgroups. In the subgroup of AIBC versus SA, SA had a lower superficial infection rate than AIBC (P= 0.01). However, in the subgroup of AIBC versus PBC, the pooled results showed that there was no statistically significant difference (P= 0.22). For deep infection, heterogeneity between the two subgroups was statistically different (P= 0.06; I2=53%), so we used a random-effect model to evaluate the deep infection rate. The total pooled results exhibited a significant statistical difference between AIBC and control treatments (RRs, 0.41; 95% CIs, 0.17 to 0.97; P= 0.04)

 

Facultative:

 

Brief description of author’s

study included both hips and knees.

Hip studies were performed in 1979 and 1981

 

Study A removed, studied no infection

 

H: Wannske 1979, not included in reference list

 

Evidence table for intervention studies (randomized controlled trials and non-randomized observational studies (cohort studies, case-control studies, case series))1

Research question: What is the place of antibiotic impregnated bone cement?

Study reference

Study characteristics

Patient characteristics 2

Intervention (I)

Comparison / control (C) 3

 

Follow-up

Outcome measures and effect size 4

Comments

Colas, 2015

Type of study: cohort

 

Setting: THA (THR) in hospital, data collected by national health insurance database

 

Country: France

 

Source of funding: unclear

Inclusion criteria: + 40 y, THR for osteoarthritis between 04/2010 and 12/2011

 

Exclusion criteria: THR for trauma or bone cancer, bilateral THR, rosthetic revision before inclusion period, no medical reimbursement after index THR, missing THR characteristics

 

 

Describe intervention (treatment/procedure/test):

 

Antibiotic impregnated cemented THR CoC, ceramic-on-ceramic; CoP, ceramic-on-polyethylene; MoM, metal-on-metal; MoP,metal-on-polyethylene;

 

Describe control (treatment/procedure/test):

 

Antibiotic free cemented THR CoC, ceramic-on-ceramic;

CoP, ceramic-on-polyethylene; MoM, metal-on-metal; MoP,metal-on-polyethylene;

Length of follow-up: median 33 months

 

Loss-to-follow-up:

Not described

 

Incomplete outcome data:

Not described

 

Outcome measures and effect size (include 95%CI and p-value if available):

 

THR revision (including any surgical reintervention in which implant or any of its components was changed or removed.

 

Antibiotic-impregnated cemented THRs had a better prognosis than uncemented THRs: cumulative revision rates were 2.4% and 3.3%, respectively (P <.001), and the multivariate adjusted hazard ratio was 0.74 (95%CI, 0.67 to 0.84; P <.001).

 

Revision risk for antibiotic-free cemented THRs was not different compared with uncemented THRs (HR, 0.95; 95% CI, 0.79 to 1.14)

 

21% used antibiotic loaded bonecement

Engesaeter, 2003

Type of study: registry

 

Setting: hospital

 

Country: Norway

 

Source of funding: unknown

 

Inclusion criteria: solely prostheses and cements with documented good long-term results in the Register. Only primary prostheses in patients with idiopathic osteoarthritis of the hip were included. We selected prostheses with high-viscosity cement of the brands Palacos with or without gentamicin or Simplex with or without colistin/ erythromycin. Lastly, only those who had received systemic antibiotic prophylaxis with cephalosporin (the first-generation cephalotin or the second-generation cefuroxime) or penicillin (cloxacillin or dicloxacillin, both semisynthetic penicillinase-resistant) were included.

 

Important patient characteristics at baseline:

 

N=22170 THA

Mean age: 72 (17-97)

29% males

Describe intervention (treatment/procedure/test):

 

A combined antibiotic prophylaxis, both systemically and in cement, was used in 71% of the operations, in 1.1% antibiotic solely in the cement and in 1.3% no antibiotic prophylaxis was used at all.

 

During the study, the prophylaxis regime was switched almost entirely to the combined regime after 1998.

Describe control (treatment/procedure/test):

 

Only systemic antibiotics

Length of follow-up: median

 

Loss-to-follow-up:

who died or emigrated during the follow-up were

identified from files provided by Statistics Norway

and the follow-up time for the prostheses in these

patients were censored on the date of death or emigration

 

Incomplete outcome data:

Not described

 

Revision:

Systemic and cement:

Systemic only: 50/15676 (0.4% 10-year revision)

Systemic only: 46/5960 (0.7% 10-year revision)

 

The revision risk for those who received only antibiotic systemically, as compared to a combined, revision was 1.4 times higher with all reasons for revision as endpoint (p <0.001), 1.3 times higher with aseptic loosening (p = 0.02) and 1.8 times higher with infection (p = 0.01)

 

 

Risk of bias table for intervention studies (observational: non-randomized clinical trials, cohort and case-control studies)

Study reference

 

 

 

(first author, year of publication)

Bias due to a non-representative or ill-defined sample of patients?1

 

 

 

(unlikely/likely/unclear)

Bias due to insufficiently long, or incomplete follow-up, or differences in follow-up between treatment groups?2

 

 

(unlikely/likely/unclear)

Bias due to ill-defined or inadequately measured outcome ?3

 

 

(unlikely/likely/unclear)

Bias due to inadequate adjustment for all important prognostic factors?4

 

 

 

(unlikely/likely/unclear)

Colas, 2015

unlikely

Unlikely

unlikely

unlikely

Engesaeter, 2003

unlikely

Unlikely

unlikely

likely

  1. Failure to develop and apply appropriate eligibility criteria: a) case-control study: under- or over-matching in case-control studies; b) cohort study: selection of exposed and unexposed from different populations.
  2. 2 Bias is likely if: the percentage of patients lost to follow-up is large; or differs between treatment groups; or the reasons for loss to follow-up differ between treatment groups; or length of follow-up differs between treatment groups or is too short. The risk of bias is unclear if: the number of patients lost to follow-up; or the reasons why, are not reported.
  3. Flawed measurement, or differences in measurement of outcome in treatment and control group; bias may also result from a lack of blinding of those assessing outcomes (detection or information bias). If a study has hard (objective) outcome measures, like death, blinding of outcome assessment is not necessary. If a study has “soft” (subjective) outcome measures, like the assessment of an X-ray, blinding of outcome assessment is necessary.
  4. Failure to adequately measure all known prognostic factors and/or failure to adequately adjust for these factors in multivariate statistical analysis.

 

Table of quality assessment for systematic reviews of RCTs and observational studies

Based on AMSTAR checklist (Shea, 2007; BMC Methodol 7: 10; doi:10.1186/1471-2288-7-10) and PRISMA checklist (Moher, 2009; PLoS Med 6: e1000097; doi:10.1371/journal.pmed1000097)

Study

 

 

 

 

First author, year

Appropriate and clearly focused question?1

 

 

 

 

Yes/no/unclear

Comprehensive and systematic literature search?2

 

 

 

Yes/no/unclear

Description of included and excluded studies?3

 

 

 

Yes/no/unclear

Description of relevant characteristics of included studies?4

 

 

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?5

 

 

 

 

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?6

 

 

 

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?7

 

Yes/no/unclear

Potential risk of publication bias taken into account?8

 

 

 

Yes/no/unclear

Potential conflicts of interest reported?9

 

 

 

Yes/no/unclear

Parvizi, 2008

yes

yes

Unclear

no

unclear

Described, but not provided

yes

yes

No

Wang,

yes

yes

Yes

yes

unclear

no

yes

yes

no

 

  1. Research question (PICO) and inclusion criteria should be appropriate and predefined.
  2. Search period and strategy should be described; at least Medline searched; for pharmacological questions at least Medline + EMBASE searched.
  3. Potentially relevant studies that are excluded at final selection (after reading the full text) should be referenced with reasons.
  4. Characteristics of individual studies relevant to research question (PICO), including potential confounders, should be reported.
  5. Results should be adequately controlled for potential confounders by multivariate analysis (not applicable for RCTs).
  6. Quality of individual studies should be assessed using a quality scoring tool or checklist (Jadad score, Newcastle-Ottawa scale, risk of bias table et cetera).
  7. Clinical and statistical heterogeneity should be assessed; clinical: enough similarities in patient characteristics, intervention and definition of outcome measure to allow pooling? For pooled data: assessment of statistical heterogeneity using appropriate statistical tests (for example Chi-square, I2)?
  8. An assessment of publication bias should include a combination of graphical aids (for example funnel plot, other available tests) and/or statistical tests (for example Egger regression test, Hedges-Olken). Note: If no test values or funnel plot included, score “no”. Score “yes” if mentions that publication bias could not be assessed because there were fewer than 10 included studies.
  9. Sources of support (including commercial co-authorship) should be reported in both the systematic review and the included studies. Note: To get a “yes,” source of funding or support must be indicated for the systematic review AND for each of the included studies.

Considerations

The most commonly used antibiotic in cement is gentamicin, which is commercially available and has broad-spectrum activity and is effective against the main bacterial causes of deep infection. Since revision risk is lowest if antibiotic-impregnated cement is combined with systemic antibiotic prophylaxis, as shown by Engeseater (2003), the working group recommends always using systemic antibiotic prophylaxis too.

Authorization date and validity

Last review : 12-02-2019

Last authorization : 12-02-2019

Module

Party in control

Year of authorization

Next assessment of actuality

Frequency of assessment actuality

Which party/parties monitors actuality

Important factors that might lead to change in recommendations

Antibiotic-impregnated bone cement

NOV

2018

2023

Eens in de vijf jaar

NOV

-

Initiative and authorization

Initiative : Nederlandse Orthopaedische Vereniging

Authorized by:
  • Koninklijk Nederlands Genootschap voor Fysiotherapie
  • Nederlandse Orthopaedische Vereniging
  • Nederlandse Vereniging voor Klinische Geriatrie
  • Nederlandse Vereniging voor Medische microbiologie

General details

The development of this guideline was funded by the Stichting Kwaliteitsgelden Medisch Specialisten (SKMS; Foundation for Quality Funding for Medical Specialists).

Scope and target group

Aim of the guideline

The main purpose of the guideline is to provide the best possible care to patients with osteoarthritis of the hip, by informing optimal treatment decisions and reducing unwarranted variation in the delivery of care and long-term failure of the implants.

 

Envisaged users of the guideline

This guideline was developed for all Dutch healthcare providers of patients with osteoarthritis of the hip.

Members of the guideline panel

This guideline was developed and sponsored by the Netherlands Orthopaedic Association (NOV), using government funding from the Quality Funding for Medical Specialists (Stichting Kwaliteitsgelden Medisch Specialisten in the Netherlands, SKMS). Patient participation was cofinanced by the Quality Funding Patient Consumers (Stichting Kwaliteitsgelden Patiënten Consumenten, SKPC) within the program ‘Quality, insight and efficiency in medical specialist care’ (Kwaliteit, Inzicht en Doelmatigheid in de medisch specialistische Zorg, KIDZ). The early preparative phase started in October 2016. The guideline was officially authorised by the Netherlands Orthopaedic Association on February 12, 2019. Decisions were made by consensus. At the start of guideline development, all working group members completed conflict of interest forms.

 

Members of the guideline development working group

  • Dr. B.A. Swierstra, orthopaedic surgeon, Sint Maartenskliniek, Nijmegen, NOV, Chair
  • Dr. R.H.M. ten Broeke, orthopaedic surgeon, Maastricht University Medical Centre, NOV
  • Drs. P.D. Croughs, medical microbiologist, Erasmus University Medical Center, NVMM
  • Dr. R.A. Faaij, geriatrician, Diakonessen Hospital, Utrecht, NVKG
  • Dr. P.C. Jutte, orthopaedic surgeon, University Medical Center Groningen, NOV
  • D.E. Lopuhaä, policy worker patient advocacy, Dutch Arthritis Society
  • Dr. W.F.H. Peter, physiotherapist, Leiden University Medical Center, KNGF
  • Dr. B.W. Schreurs, orthopaedic surgeon, Radboud University Medical Centre, Nijmegen, NOV
  • Dr. S.B.W. Vehmeijer, orthopaedic surgeon, Reinier de Graaf Hospital, Delft, NOV
  • Dr. A.M.J.S. Vervest, orthopaedic surgeon, Tergooi Hospital, Hilversum, NOV
  • J. Vooijs†, patient with osteoarthritis, National Association ReumaZorg Nederland
  • Drs. G. Willemsen-de Mey, chairperson, National Association ReumaZorg Nederland

 

Readers:

  • S. Nijssen, medical microbiologist, VieCuri Medical Center, Venlo, NVMM
  • R.J. Rentenaar, medical microbiologist, University Medical Center, Utrecht, NVMM
  • Dr. A.T. Bernards, medical microbiologist, Leiden University Medical Center, NVMM

 

With the help of:

  • Dr. M.A. Pols, senior advisor, Knowledge Institute of the Dutch Association of Medical Specialists
  • Dr. M.L. Molag, advisor, Knowledge Institute of the Dutch Association of Medical Specialists
  • A.L.J. Kortlever- van der Spek, junior advisor, Knowledge Institute of the Dutch Association of Medical Specialists
  • M.E. Wessels MSc, clinical librarian, Knowledge Institute of the Dutch Association of Medical Specialists

Declaration of interest

At the start of the project, the members of the working group have declared in writing if, in the last five years, they have held a financially supported position with commercial businesses, organisations or institutions that may have a connection with the subject of the guidelines. Enquiries have also been made into personal financial interests, interests pertaining to personal relationships, interests pertaining to reputation management, interests pertaining to externally financed research, and interests pertaining to valorisation of knowledge. These declarations of interest can be requested from the secretariat of the Knowledge Institute of the Dutch Association of Medical Specialists. See below for an overview.

 

Werkgroeplid

Mogelijke conflicterende belangen met betrekking tot deelname werkgroep

Toelichting

Dr. B.W. Schreurs

Presentaties voor Stryker over de Exeter totale heupprothese (educational fee naar afdeling)

Doet reviews voor DEKRA KEMA (betaald)

Voorzitter European Hip Society (onbetaald)

Voorzitter wetenschappelijke adviesraad LROI (onbetaald)

Voorzitter adviesraad botbank Sanquin (onbetaald)

Lid Commissie Orthopedisch Implantaten Classificatie NOV (onbetaald)

 

Dr. P.C. Jutte

Hoofdonderzoeker LEAK-studie (ZonMW)

Voorzitter werkgroep weke delen en bottumoren

Lid werkgroep orthopedische infecties NOV

Lid werkgroep bottumoren NOV

Lid commissie beentumoren Nederland

Lid onderwijscommissie NOV

Lid medische adviesraad patientvereniging Sarcoma NL

 

D.E. Lopuhaä

Geen belangen

 

Dr. R.H.M. ten Broeke

Voorzitter werkgroep "Heup" (Dutch Hip Society) NOV sinds 2015 (onbetaald)

Daarvoor gedurende 3 jaar reeds bestuurslid van deze werkgroep (onbetaald)

Klinisch onderzoek gefinancierd door firma Stryker (RSA en PET-CT-onderzoek bij vergelijking van 2 ongecementeerde cupdesigns) (onbetaald)

 

Dr. W.F.H. Peter

Geen belangen

 

Dr. P.D. Croughs

Geen belangen

 

Dr. S.B.W. Vehmeijer

Directeur Orthoparc (onbetaald)

Bestuurslid Dutch Hip Society (onbetaald)

National Representative European Hip Society (onbetaald)

Consulent Zimmer Biomet (betaald)

 

Dr. B.A. Swierstra

Voorzitter Stichting OrthoResearch (onbetaald)

Advisory Board Arthroplasty Watch (onbetaald)

Lid Wetenschappelijke Advies Raad Landelijke Registratie Orthopaedische Implantaten (onbetaald)

Board of Directors International Society of Orthopaedic Centers (onbetaald)

Coeditor Acta Orthopaedica (onkostenvergoeding)

 

Dr. R.A. Faaij

Geen belangen

 

Dr. A.M.J.S. Vervest

Lid-beroepsgenoot Regionaal Tuchtcollege voor de Gezondheidszorg Den Haag (betaald)

Voorzitter Centrale Opleidings Commissie Tergooi (onbetaald)

 

J. Vooijs

Geen belangen

 

Drs. G. Willemsen – de Mey

Geen belangen

 

Meelezers

Drs. S. Nijssen

ISO 15189 auditor, betaald door RvA

 

Dr. R.J. Rentenaar

Commissie bacteriologie Stichting Kwaliteitsbewaking Medische Laboratoria (SKML) (tegen onkostenvergoeding).

Verschillende producenten stellen soms kleine hoeveelheden van producten ter beschikking kosteloos of tegen gereduceerd tarief t.b.v. verificatie doeleinden

 

Dr. A.T. Bernards

Geen belangen

 

Patient involvement

Attention was paid to the patients’ perspective by participation in the working group of the Dutch Arthritis Society and National Association ReumaZorg Nederland. In addition, the Patients Federation Netherlands assessed the draft guideline during the consultation phase and made suggestions for improvement of the guideline.

Method of development

Evidence based

Implementation

Recommendation

Time needed for implementation:
<1 year,

1 to 3 years or

>3 years

Expected effects on costs

Conditions for implementation

Possible barriers to implementation1

Actions for implementation2

Reponsibility for these actions3

Other remarks

All

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

Methods and proces

The guideline was developed in agreement with the criteria set by the advisory committee on guideline development of the Dutch Association of Medical Specialists (Medisch Specialistische Richtlijnen 2.0; OMS 2011), which are based on the AGREE II instrument (Brouwers (2010); www.agreetrust.org). The guideline was developed using an evidence-based approach endorsing GRADE methodology, and meeting all criteria of AGREE-II. Grading of Recommendations Assessment, Development and Evaluation (GRADE) is a systematic approach for synthesising evidence and grading of recommendations offering transparency at each stage of the guideline development (Guyatt, 2011; Schünemann, 2013).

 

The guideline development process involves a number of phases: a preparatory phase, development phase, commentary phase, and authorisation phase. After authorisation, the guideline has to be disseminated and implemented and its uptake and use have to be evaluated. Finally, the guideline has to be kept up-to-date. Each phase involves a number of practical steps Schünemann, (2014).

 

As a first step in the early preparatory phase, a broad forum discussion was held and all relevant stakeholders were consulted to define and prioritise the key issues the recommendations should address. Subsequently, the methodologist together with the chairman of the working group created a draft list of key issues, which was extensively discussed in the working group.

 

Despite aiming for an update of the guideline from 2010, due to financial constraints not all clinical questions from the former edition could be updated, so it was decided to perform a so-called modular update. Selecting modules with a higher priority for update formed part of this discussion and selection process. This resulted in the following approach.

 

Modules that were updated:

  • Indications for primary total hip arthroplasty.
  • Type of bearing (part of the module surgical techniques).
  • Diameter of the head (part of the module surgical techniques).
  • Surgical approach (part of the module surgical techniques).
  • Systemic antibiotics (part of the module perioperative care in primary total hip arthroplasty).
  • Antibiotic-impregnated bone cement (part of the module perioperative care in primary total hip arthroplasty).
  • Preoperative decolonisation (part of the module perioperative care in primary total hip arthroplasty).
  • Routine follow-up (part of the module postoperative care).

 

Modules considered still valid:

  • cemented versus uncemented hip prosthesis (part of the module surgical techniques in primary total hip arthroplasty).

 

Modules removed from the guideline:

  • Resurfacing hip prosthesis (part of the module surgical techniques in primary total hip arthroplasty).
  • Minimally invasive surgery (part of the module surgical techniques in primary total hip arthroplasty).
  • Guidelines for MRSA carriers (part of the module perioperative care in primary total hip arthroplasty).

 

Modules that were replaced by a reference to related guidelines:

  • Hematogenous infection (part of the module postoperative care).
  • Prevention of thrombo-embolic complications (part of the module perioperative care in primary total hip arthroplasty).
  • Physcial therapy (part of the module perioperative care in primary total hip arthroplasty).

 

Modules not updated because guidelines are expected soon:

  • Anaesthesiological technique (part of the module perioperative care in primary total hip arthroplasty).

 

Modules that were added:

  • Patient Reported Outcome Measures.
  • Place and organisation of fasttrack.
  • Organization of care for frail elderly.

 

The selected (high priority) issues were translated into carefully formulated clinical questions, defining patient/problem, intervention, and prioritising the outcomes relevant for decision-making.

 

The literature was systematically searched using the databases MEDLINE (Ovid), Embase and the Cochrane Database of Systematic Reviews. Selection of the relevant literature was based on predefined inclusion and exclusion criteria and was carried out by a member of the working group in collaboration with the methodologist. For each of the clinical questions, the evidence was summarised by the guideline methodologist using the GRADE approach: a systematic review was performed for each of the relevant outcomes and the quality of evidence was assessed in one of four grades (high, moderate, low, very low) by analysing limitations in study design or execution (risk of bias), inconsistency of results, indirectness of evidence, imprecision, and publication bias. The evidence synthesis was complemented by a working group member considering any additional arguments relevant to the clinical question. Evidence synthesis, complementary arguments, and draft recommendations were extensively discussed in the working group and final recommendations were formulated. Final recommendations are based on the balance of desirable and undesirable outcomes, the quality of the body of evidence across all relevant outcomes, values and preferences, and (if relevant) resource use. The strength of a recommendation reflects the extent to which the guideline panel was confident that desirable effects of the intervention outweigh undesirable effects, or vice versa, across the range of patients for whom the recommendation is intended. The strength of a recommendation is determined by weighting all relevant arguments together, the weight of the body of evidence from the systematic literature analysis, as well as the weight of all complementary arguments. Guideline panels must use judgment in integrating these factors to make a strong or weak recommendation. Thus, a low quality of the body of evidence from the systematic literature analysis does not exclude a strong recommendation, and weak recommendations may follow from high quality evidence Schünemann, (2013).

 

After reaching consensus in the working group, the draft guideline was subjected to peer review by all relevant stakeholders. Amendments were made and agreed upon by the working group, and the final text was presented to the Netherlands Orthopaedic Association (NOV), the Royal Dutch Society for Physical Therapy (KNGF), the Dutch Society of Medical Microbiology (NVMM) and the Dutch Geriatrics Society (NVKG) for formal authorisation and to the National Association ReumaZorg Nederland and the Dutch Arthritis Society for approval. The final guideline was approved by the National Association ReumaZorg Nederland and the Dutch Arthritis Society, and was officially authorised by the Netherlands Orthopaedic Association, the Royal Dutch Society for Physical Therapy, the Dutch Society of Medical Microbiology and the Dutch Geriatrics Society. The guideline was published and is freely accessible in the Dutch guideline database (Richtlijnendatabase, www.richtlijnendatabase.nl). The Dutch guideline database has a modular structure, with each clinical question as a separate entry, thus allowing for modular updates.

 

References

Brouwers M, Kho ME, Browman GP, et al. AGREE II: Advancing guideline development, reporting and evaluation in healthcare. Can Med Assoc J. Dec;182:E839-842; doi: 10.1503/cmaj.090449.

Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology. 2011;64 383–394. (doi:10.1016/j.jclinepi.2010. 04.026).

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from www.guidelinedevelopment.org/ handbook.

Schünemann HJ, Wiercioch W, Etxeandia I, et al. Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise. CMAJ. 2014;186(3):E123-42. doi: 10.1503/cmaj.131237. Epub 2013 Dec 16. PubMed PMID: 24344144.

OMS, Orde van Medisch Specialisten. Eindrapport Medisch Specialistische Richtlijnen 2.0. Available from: https://www.demedischspecialist.nl/onderwerp/raad-kwaliteit. 2011.

Search strategy

Searches are available upon request. Please contact the Richtlijnendatabase.