1. No category

Seminars in Arthritis and Rheumatism 43 (2013) 195–203
Contents lists available at ScienceDirect
Seminars in Arthritis and Rheumatism
journal homepage: www.elsevier.com/locate/semarthrit
Where and how to inject the knee—A systematic review☆, ☆☆
Nasimah Maricara,n, Matthew J. Parkesa, Michael J. Callaghana, David T. Felsona,b,c,
Terence W. O'Neilla,b
a
Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Oxford Road, Manchester, UK
NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre,
Manchester, UK
c
Clinical Epidemiology Unit, Boston University School of Medicine, Boston, MA
b
a r t i c l e in fo
Keywords:
Osteoarthritis of the knee
Clinical trials
Injection
Aspiration
Accuracy
Systematic review
a b s t r a c t
Objectives: The knee can be injected at different anatomic sites with or without image-guidance. We
undertook a systematic review to determine the accuracy of intra-articular knee injection (IAKI) and
whether this varied by site, use of image-guidance, and experience of injectors, and whether accuracy of
injection, site, or use of image-guidance influenced outcomes following IAKIs.
Methods: Medline, Embase, AMED, CINAHL, Web of Knowledge, Cochrane Central Registers for Controlled Trials up to Dec 2012 were searched for studies that evaluated either accuracy of IAKIs or
outcomes related to accuracy, knee injection sites, or use of image-guidance. Within-study and betweenstudy analyses were performed.
Results: Data from 23 publications were included. Within-study analyses suggested IAKIs at the superomedial patellar, medial midpatellar (MMP), superolateral patellar (SLP) and lateral suprapatellar bursae
sites were more accurate when using image-guidance than when blinded (ranges of pooled risk difference
0.09–0.19). Pooling data across studies suggested blinded IAKIs at the SLP site were most accurate (87%)
while MMP (64%) and anterolateral joint line (ALJL) sites were (70%) least accurate. Overall about one in five
blinded IAKIs were inaccurate. There was some evidence that experience of the injector was linked with
improved accuracy for blinded though not image-guided injections. Based on a small number of studies,
short but not longer-term outcomes for ultrasound-guided were found to be superior to blinded IAKIs.
Conclusions: Image-guided IAKIs are modestly more accurate than blinded IAKIs especially at the MMP and
ALJL sites. Blinded injections at SLP site had good accuracy especially if performed by experienced injectors.
Further studies are required to address the question whether accurate localization is linked with an
improved response.
& 2013 The Authors. Published by Elsevier HS Journals, Inc. All rights reserved.
Introduction
The knee is one of the commonest target joints for intraarticular injection therapy [1–4]. There are a number of possible
anatomic injection sites [5–7]. Clinicians' choice of technique is
often influenced by their experience and training.
It seems likely that increased accuracy of localization of the
injection within the joint should improve treatment response.
However, unlike shoulder injections where there is established
evidence for using image-guided injections [1,8–12], the evidence
☆
This is an open-access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided
the original author and source are credited.
☆☆
This review was funded by a program grant from Arthritis Research UK (Grant
Number 18676). Nasimah Maricar is funded by a Clinical Doctoral Fellowship award
from the National Institute for Health Research.
n
Corresponding author.
E-mail address: [email protected] (N. Maricar).
base for needle-guidance during intra-articular knee injections
(IAKI) is weaker. It remains uncertain whether approaches for
localization such as using air arthrogram [13,14], fluoroscopy [15],
ultrasound [16,17], and magnetic resonance imaging (MRI) [18]
actually improve IAKI accuracy. Also it remains unclear whether
improved accuracy is associated with better clinical response.
We undertook a systematic review with the aim of determining—
(i) the accuracy of IAKI and whether this varied by site, imaging, and
experience of injectors and, (ii) whether accuracy, site of injection, or
the use of image-guidance were linked with therapeutic response.
We also undertook a meta-analysis of the accuracy of “blinded”
(without image-guidance) vs guided IAKI (with image-guidance).
Methods
Search strategies
Publications that looked at accuracy of IAKIs or clinical outcome
associated with intra-articular needle placement, delivered
0049-0172/$ - see front matter & 2013 The Authors. Published by Elsevier HS Journals, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.semarthrit.2013.04.010
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N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
blinded or guided, or at varying knee injection sites were identified from searching six databases up to Dec 2012: Medline (1948
onwards), Embase (1974 onwards), AMED (1985 onwards), Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus
(1937 onwards), Web of Science (1950 onwards), and the Cochrane
Central Registers for Controlled Trials. The databases were
searched individually for all possible terms and combination of
terms to accommodate differences in their search engines. All
medical subject-heading searches (MeSH) were explored when
possible. The key terms used in combination (“AND”) were knee,
intra-articular, injection, aspiration, trials, and accuracy.
observational studies, “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) checklist of 22 items was
used to assess quality [25] with close reference to further elaboration and explanation of the criteria given in another publication
of the STROBE statement [26]. For non-RCT, quality was assessed
using the “Transparent Reporting of Evaluations with Nonrandomized Designs” (TREND) checklist [27]. The data were
extracted independently by two reviewers (N.M. and M.J.P.). Two
assessors (N.M. and M.J.C.) independently assessed and scored the
publications for quality and reached consensus in cases of
disagreement.
Study selection criteria
Data extraction and analyses
In this review, injection “sites” refer to specific areas in the knee
for needle entry and injection “approaches” refer to techniques of
delivering the injections or aspirations including angling of the
needle or position of the knee, flexed or extended. Guided IAKIs
included any needle-guidance techniques to assist getting into the
joint such as injections or aspirations aided by ultrasound, fluoroscopy, or air-arthrography. For assessing accuracy of IAKI, we
included studies that used participants with knee osteoarthritis
(OA), inflammatory arthritis, mixed samples of OA and inflammatory arthritis, those without knee pathologies, and cadavers. For
formal comparison of blinded and guided IAKI, we included
studies that used at least two treatments arms; one delivering
blinded injection at a particular site and another using guided
injection at the same site, allowing within-study comparison. We
found that most studies provided information about one treatment
arm only. To maximize utilization of the available data, we therefore included a between-study comparison of the various injection
sites pooling the accuracy of blinded and guided IAKIs separately.
There were too few data to look at outcome in relation to accuracy
and knee injection sites; however, we were able to pool data in
relation to the influence of image-guidance on outcome. Outcome
measures relating to treatment response were not specified a
priori.
A fixed-effects meta-analysis was used to pool those studies
that evaluated a specific injection site under both blinded and
guided conditions within the same trial (within-study analyses).
Heterogeneity in trial outcomes was assessed using the I2 statistic.
Results of other studies evaluating accuracy of specific injection
sites were also pooled (between-study analyses). Accuracy was
assessed as the percentage of those injected in which the injection
was correctly localized. For within-study comparisons, difference
in accuracy (guided vs blinded) was assessed using absolute risk
difference (ARD) with associated 95% confidence intervals (CI),
where the risk ratio is the “risk” of an accurate injection in the
guided group to the “risk” of an accurate injection in the blinded
group. For between-study comparisons, difference in accuracy
between groups was assessed also using the chi-square statistic
and relative risk (RR). We used a fixed-effects meta-analysis to
pool data looking at outcomes in relation to use of image-guidance
(ultrasound). Results were considered significant if p-values were
less than 0.05 (two sided) or if the 95% CI of the RR and ARD did
not include one and zero, respectively.
Results
Search outcome
Knee joint injection accuracy
Accurate IAKI occurs when the needle is placed within the
intra-capsular joint space and inaccurate injection when the
needle is placed extra-articularly or gets embedded into other
intra-capsular tissues such as plica. To determine the accuracy of
IAKI, a number of approaches are available such as injection of
contrast or air with radiography [13,14], sonography [19] or
fluoroscopy [20], magnetic resonance imaging (MRI) [18], surgical
confirmation of intra- or extra-articular placement of drugs
[21,22], and for aspiration successful removal of synovial fluid.
There is no gold standard for assessing accuracy of IAKI. It is
recognized that all these techniques are subject to a degree of
observer error in evaluation of the images while surgical confirmation is too invasive for routine use. In this review, we
included all studies that made an independent attempt to corroborate intra-articular placement including successful aspiration of
synovial fluid. For this review, the results on accuracy of the sites
of injection were tabulated by injection site and also whether
image-guidance was used or not. We did not look separately at
accuracy by method of image-guidance.
Quality assessment
For randomized controlled trials (RCTs), study quality was
graded using the Jadad score [23]. Concealment to treatment
allocation was scored as adequate, inadequate, or unclear if there
was insufficient information to make the judgment [24]. For
From all databases, 710 publication records were retrieved and
302 duplicates eliminated (Fig. 1). Text-words from 408 records
were screened, and of these, 296 records failed to meet study
selection criteria. Of the 112 abstracts read, 56 were not relevant
and were excluded. A further 56 full-text articles were read for
eligibility. Of these 33 were rejected for not evaluating accuracy of
IAKI sites, blinded or guided IAKIs, or clinical outcome associated
with intra-articular needle placement. Twenty-three publications
finally met the inclusion criteria (Fig. 1); some of these addressed
accuracy only, others both accuracy and treatment outcome
(Table 1).
Twelve of 23 studies were RCTs, three non-RCTs, and eight
observational studies. Twenty-two publications addressed accuracy of IAKIs and/or aspiration, seven assessed accuracy of IAKIs at
different sites [14,15,21,22,28–30], four at one injection site
[20,31–33], and 13 compared blinded and guided IAKIs
[2,13,19,20,28,30,34–40]. Of the six studies that reviewed clinical
outcomes, one was pertaining to accuracy of IAKI [29], two
compared between different knee injection sites [28,33], and three
compared outcomes between guided and blinded IAKIs [40,41]
(Table 1). In two papers, the injection site was not specified during
blinded IAKIs [2,4]. There were also two studies that investigated
knee injections performed at the same site but using different
approaches depending on the angling of the needle or the position
of the knee, flexed or extended [28,29]; though in one of these
studies, the accuracy relating to each approach was not formally
assessed [28]. In three papers [14,20,30] the authors were
N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
197
Records identified from all sources (n=710)
MEDLINE
AMED
Embase
Cochrane Register
Web of Knowledge
CINAHL
199
122
110
117
155
5
Others
2
Duplicates (n=302)
No. of records screened
408
Fail to meet study selection criteria (n=296)
No. of abstract read
112
Not relevant to study questions (n=56)
No. of full text read
56
No. of full text articles excluded (n=33), reasons:5
• Reviews of Treatment
• Injection not in knee joint
5
• Did not consider accuracy and comparison
of outcomes of knee injections
23
No. of studies for qualitative synthesis n=23:
-
For IAKI approaches and accuracy = 22
-
For IAKI clinical outcome = 6
Fig. 1. Summary of search results.
contacted to provide clarity relating to accuracy and injection sites.
The required information was obtained for one of the studies [20];
in the others [14,30], site of knee injections was designated as
unknown.
Data quality
For the 12 RCTs, only five had Jadad scores of three and above
[2,29,35–37] and were deemed as high-quality trials [42] and five
had adequate allocation concealment [2,29,35,36,39] (see Supplementary Tables S1–S3). Others were single-blinded trials where
either patients or injectors were not blinded to the intervention
groups. For the observational studies, seven of eight studies
fulfilled 10–18 of the 22 STROBE criteria [4,13,19,21,31,32,38],
while all three non-randomized trials had TREND scores of 10–
15 of 22 [14,15,34] (see Supplementary Tables S1–S3).
Knee joint injection sites and approaches
Publications included in this review sometimes used different
terms to describe the sites of injections, but by using the enclosed
descriptions of how the injections were performed including
diagrams or pictures, we were able to identify eight different
injection sites. These included medial injection techniques such as
over the anteromedial joint line (AMJL), medial midpatellar
(MMP), and superomedial patellar (SMP) and lateral injection
techniques over the anterolateral joint line (ALJL), lateral
midpatellar (LMP), superolateral patellar (SLP), lateral suprapatellar bursa (LSB), and also infrapatellar (IFP) (Fig. 2). In five
publications sites were classified as “unknown.” Infrapatellar site
was used least and evaluated in one publication only.
Thirteen approaches at eight sites were described during
blinded IAKIs. For anteromedial joint line injection, the needle
was inserted within the portal formed by inferomedial patellar
border, patellar tendon, and medial tibial plateau, directing the
needle toward intercondylar notch with the knee extended [21] or
flexed 301 [29] or 901 [15,29]. With the medial midpatellar, the
injection was made between patella and patellar groove of femur
at mid medial patellar junction with the knee extended
[21,33,37,39]. The superomedial patellar injection was performed
with the needle inserted in a 451 cephalomedial to caudolateral
direction between the femoral condyle and the lateral border of
patella at the superior one-third margin of the patella with the
knee extended [38].
In contrast, the anterolateral joint line injection could be
performed using four approaches with the needle inserted within
the portal formed by inferolateral patellar border, patellar tendon,
and lateral tibial plateau directing the needle towards intercondylar notch with the knee flexed [15,21] or directing the needle
toward medial femoral condyle with the knee extended [28] or
flexed between 301 and 401 [20] or flexed to 901 [28]. For lateral
midpatellar approach, the injection was made between patella and
patellar groove of femur at mid lateral patellar junction with the
knee in an extended position [15,21,39]. In the superolateral
patellar injection, the needle was inserted 1 cm above and 1 cm
198
N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
Table 1
Published papers
Authors
Phenotype
Intervention
Method for assessing
accuracy
Assessment
Balint et al.
[34]
Bliddal [13]
Knee OA and RA
Successful aspiration
Accuracy: blinded (unknown site) vs ultrasound-guided (via LSB)
Air on XR
Accuracy and outcome: blinded vs air-arthrography guided via SLP
Bum Park et al.
[35]
Chavez-Chiang
et al. [28]
Cunnington
et al. [2]
Curtiss et al.
[36]
Esenyel et al.
[21]
Glattes et al.
[14]
Im et al. [37]
Jackson et al.
[15]
Jones et al. [4]
Lopes et al. [31]
Knee OA
Aspiration of synovial
fluid
Steroid/local
anesthetic/air
Hyaluronic acid
XR þ contrast
Accuracy: blinded vs ultrasound-guided via LSB
Ultrasound
Inflammatory
arthritis
Cadaveric knees
Steroid/local
anesthetic
Aspiration of synovial
fluid
Methylene blue
XR þ contrast
Treatment outcome: blinded injection via LMP and LJL (knee extended)
Accuracy: ultrasound-guided via LJL (knee flexed)
Accuracy and outcome: blinded vs ultrasound-guided
Dissection
Accuracy: blinded (SLP) vs ultrasound-guided (LSB)
Cadaveric knees
Methylene blue
Dissection
Accuracy: blinded injection via MJL, MMP, LJL, and LMP
Knees needing
injection
Knee OA
Knee OA
Local anesthetic
Hyaluronic acid
Hyaluronic acid
XR þ contrast
Accuracy: blinded injection via SLP
“Squishing sound” test
XR þ contrast
Accuracy: blinded vs ultrasound-guided via MMP
Fluoroscopy
Accuracy: blinded injection via AM, AL, and LMP
Knee OA and RA
Inflammatory
arthritis
Knee OA
Steroid
Steroid
XR þ contrast
XR þ contrast
Local anesthetic
Knee OA
Hyaluronic acid
XR þ contrast “Backflow Accuracy: blinded injection via SLP
of fluid” test
Fluoroscopy
Accuracy: blinded vs fluoroscopy-guided via SMP
Knee OA
Knee OA
Knee OA
Steroid/local
Hyaluronic acid/local
anesthetic/air
Steroid
Cadaveric knees
Methylene blue
Knee OA and RA
Aspiration of synovial
fluid
Steroid/local
anesthetic
Hyaluronic acid
Successful aspiration
Accuracy and outcome: blinded vs ultrasound-guided aspiration via LSB
–
Outcome: blinded vs ultrasound-guided via AMJL
XR þ contrast
Accuracy and outcome: blinded injection via MJL (flexed 30◦), MJL (flexed 90◦),
and LMP
Methylene blue
XR þ contrast
Accuracy: fluoroscopy-guided via ALJL
Aspiration of synovial
fluid
Hyaluronic acid/
methylene blue
Successful aspiration
Accuracy and outcome: blinded vs ultrasound-guided
Arthroscopy
Accuracy: blinded injection via SMP, SLP, and LJL
Luc et al. [32]
Myung et al.
[38]
Park et al. [39]
Qvistgaard
et al. [19]
Shah and
Wright [33]a
Shah and
Wright [33]b
Sibbitt et al.
[40]
Sibbitt Jr et al.
[41]
Toda and
Tsukimura
[29]
Waddell et al.
[20]
Wiler et al. [30]
Wind and
Smolinski
[22]
Knee OA
Knee OA
Knee OA
Knee OA
Non-arthritic
kneesc
Effused knees
Knees undergoing
arthroscopy
Accuracy and outcome: blinded injection
Accuracy and outcome: blinded injection
XR þ contrast
Accuracy: ultrasound-guided via MMP, LMP, and SLP
Air on ultrasound image Accuracy: ultrasound-guided via SLP
Dissection
Outcome: blinded M vs IFP injection
Accuracy: blinded injection via IFP
Abbreviations: OA, osteoarthritis; RA, rheumatoid arthritis; M, medial; L, lateral; MP, medial patellar; IFP, infrapatellar; AM, anteromedial; AL, anterolateral; MMP, medial
midpatellar; SMP, superomedial patellar; MJL, medial joint line; LMP, lateral midpatellar; SLP, superolateral patellar; LJL, lateral joint line; LSB, lateral suprapatellar bursa.
a
b
c
Trial comparing outcomes of knee injections delivered at two sites in 36 patients.
Trial to determine infrapatellar injection accuracy using four OA cadaveric knees.
Six of the 11 participants had a history of knee complaints. Shaded row: within-study analyses.
lateral to superolateral margin of patella in a 451 angle cephalolateral to caudomedial direction with the knee extended
[14,22,29,32,39]. During lateral knee injection into the suprapatellar bursa, the needle was inserted from superolateral aspect
of patella, one-fingerbreadth above and one-fingerbreadth lateral
to the patella with the knee extended [35,40]. The infrapatellar
injection was performed over the lateral condyle of tibia with the
needle directed upwards and medially while the knee was in a
flexed position [33].
For studies that performed guided IAKIs, two medial sites,
MMP [37,39] and SMP [38] and four lateral sites, ALJL [20,28], LMP
[39], SLP [13,39], and LSB [2,19,34–36,40] were used. The lateral
sites were more commonly used during guided IAKIs while
blinded injections were more frequently delivered through
medial sites.
Within-study analyses
Guided vs blinded IAKIs
Five studies were included in the within-study analyses and
these involved four injection sites (Fig. 3).
Statistical heterogeneity of the five pooled studies was small (I²
¼ 28%). For the two pooled studies on LSB using ultrasoundguided IAKIs, there was no statistical heterogeneity (I² ¼ 0%).
Guided IAKIs at MMP, SMP, LSB, and SLP sites were found to be
significantly more accurate (ranges pooled ARD 0.09–0.19; p o
0.05) than their respective blinded injections (Fig. 3). The accuracy
of medial sites (ranges of pooled ARD 0.18–0.19) was improved to a
greater extent than the lateral sites (pooled ARD ranges 0.09–0.14)
by guided injections. Of all the four sites, compared to a blinded
N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
199
Fig. 2. Injection sites in knee.
injection, accuracy at SLP showed least improvement following
image-guidance using air-arthrography.
Between-study analyses
Accuracy: Influence of injection site, image-guidance, and experience
of clinician
Blinded
Of the three medial sites at which blinded injections were
performed, the SMP site was linked with greatest accuracy of
injection (82%), followed by AMJL (74%) and MMP (64%) (Table 2).
One publication reported that injections performed at AMJL with
knees flexed to 301 was more accurate (p ¼ 0.035) than knees
flexed to 901 [29].
Of the four lateral sites at which blinded injections were
performed, the SLP site was linked with greatest accuracy of
injection (87%), followed by LMP (84%), LSB (83%), and ALJL
(70%) (Table 2).
accuracy of IAKI. The study found that the injector's experience
influenced the accuracy rate of blinded injections at the SLP site;
accuracy rate of 55% (95% CI 34–74) for the less experienced
injector compared to 100% (95% CI 81–100) for the more
experienced injector [36]. Luc et al. [32], however, in their trial
of 33 knee injections reported a similar accuracy for blinded
injections at the SLP site for a clinical fellow (96%) and
experienced rheumatologist (100%). Two other publications that
included “unknown” sites of blinded knee injections found similar
accuracy irrespective of the level of experience, seniority, and
training [2,4].
Guided. Similar accuracy was found for less experienced junior
clinicians and injectors with more experience during guided IAKIs
[2,32]. Cunnington et al. [2] reported 91% accuracy when a
research fellow performed the injections using sonographicguidance while Luc et al. [32] reported 100% accuracy when a
medical fellow used “backflow of injected fluid” during IAKIs to
confirm intra-articular placement of needles.
Guided
Of the two medial sites investigated during guided IAKIs, the
SMP site was linked with greatest accuracy (100%) while MMP
improved to 86% with image-guidance (Table 2). Based on a pooled
study comparison, IAKIs at the MMP (ARD 0.22; 95% CI, 0.10–0.33;
p ¼ 0.0005) and SMP sites (ARD 0.18; 95% CI, 0.14–0.22; p
o 0.0001) were significantly more accurate using imageguidance than when given blinded (Table 3). No studies evaluated
the AMJL site.
Pooling data across studies (Table 2), all four lateral sites (ALJL,
LMP, SLP, and LSB) had excellent accuracy, 95–100%, when performed guided, though the best lateral site was still the SLP. Based
on a pooled study comparison, there was a significant improvement in the accuracy of injections at LSB and SLP sites (pooled ARD
0.13–0.15; p r 0.0001) while LMP site also improved (ARD 0.12;
95% CI 0.001–0.20; p ¼ 0.05) with image-guidance (Table 3). IAKIs
at ALJL were highly more accurate when guided (ARD 0.28; 95% CI,
0.20–0.35; p o 0.0001) (Table 3).
Outcome
Experience
Blinded. Of four publications, only one study was designed
formally to investigate the impact of injectors' experience on the
In this systematic review, blinded IAKIs overall were reasonably
accurate, in particular the lateral injection sites. The use of needleguidance improved the accuracy of IAKIs significantly. There was,
Because of small numbers and differences in study design, it
was not possible to pool data from those studies that looked at
outcome associated with either accuracy or site of injection. There
were three studies that reported outcomes related to use of imageguidance (using ultrasound); one was conducted on subjects with
knee OA without effusion [41], another on OA and RA knees with
effusion [40], and a third in knees with effusion [30]. Figure 4
shows the forest plots for two of these studies that suggested
better pain reductions at 2 weeks with guided IAKIs [40,41]; no
outcome data on pain was available in the third [30]. There was no
difference in longer-term pain-relief, though duration of response
was a month longer with ultrasound-guidance [41]. Using volume
of synovial fluid aspirated as the outcome, image-guidance was
associated with greater volume aspirated (see Fig. 4).
Discussion
200
N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
Guided
Blinded
Events Total Events Total Weight
Study or Subgroup
Superolateral Patellar
56 10.2%
51
56
56
Bliddal 1999
10.2%
56
56
Subtotal (95% CI)
51
56
Total events
Heterogeneity: Not applicable
Test for overall effect: Z = 2.18 (P = 0.03)
Lateral Suprapatellar Bursa
49
41
50
48
Bum Park 2012
22
18
42
42
Sibbitt 2012
71
92
Subtotal (95% CI)
59
90
Total events
Heterogeneity: Chi² = 0.32, df = 1 (P = 0.57); I² = 0%
Test for overall effect: Z = 2.92 (P = 0.003)
Medial Mid Patellar
45
43
Im 2009
45
Subtotal (95% CI)
43
Total events
Heterogeneity: Not applicable
Test for overall effect: Z = 2.60 (P = 0.009)
34
Risk Difference
M-H, Fixed, 95% CI
Risk Difference
M-H, Fixed, 95% CI
0.09 [0.01, 0.17]
0.09 [0.01, 0.17]
9.1%
5.3%
14.3%
0.12 [0.01, 0.24]
0.18 [0.02, 0.35]
0.14 [0.05, 0.24]
44
44
8.1%
8.1%
0.18 [0.05, 0.32]
0.18 [0.05, 0.32]
368
368
67.3%
67.3%
0.19 [0.15, 0.23]
0.19 [0.15, 0.23]
34
Superomedial Patellar
298
368
368
Myung 2007
368
Subtotal (95% CI)
298
368
Total events
Heterogeneity: Not applicable
Test for overall effect: Z = 9.25 (P < 0.00001)
0.17 [0.14, 0.21]
539 100.0%
561
Total (95% CI)
442
557
Total events
Heterogeneity: Chi² = 5.59, df = 4 (P = 0.23); I² = 28%
Test for overall effect: Z = 10.08 (P < 0.00001)
Test for subgroup differences: Chi² = 5.11, df = 3 (P = 0.16), I² = 41.3%
-0.2
-0.1
0
0.1
0.2
Favors blinded injection
Favors guided injection
Fig. 3. Forest plot—Injection accuracy of guided vs blinded knee injections.
however, insufficient evidence to suggest that increased accuracy
of knee injections resulted in an improved therapeutic outcome.
The use of ultrasound-guided IAKIs though may lead to better
short-term benefit.
We found good accuracy with most lateral approaches even
when performed blinded, suggesting clinicians have a choice when
selecting injection sites over the lateral aspect of the knee.
However, due to a relatively low accuracy of ALJL injection when
undertaken blinded (70%), we suggest it might be better undertaken with image-guidance. We also found the MMP was the least
accurate site for both blinded and guided injections. A possible
explanation for this is that with the approach the needle may
engage with the medial knee plica or fat pad [3,43]. Medial
injections with a partially flexed knee are deemed anecdotally
least successful, more painful, and most likely to be loculated
[43,44]. However, although there were few studies, our review did
not find any significant difference in accuracy when injections
were performed with the knee in extension or flexion.
Accuracy of injection for ultrasound-guided injections was not
improved except with injection of the anterior lateral joint line site
The experience of injectors may influence the accuracy of
blinded injections [4,36] though further studies are needed. In
contrast, image-guided knee injections can be delivered accurately
independent of the injector's experience (including junior clinicians with a short training period) [2,32]. This perhaps indicates
that delivering an injection blinded using anatomical palpation
may require experiential learning.
From the pooled data across studies, all four lateral sites (ALJL,
LMP, SLP, and LSB) had excellent accuracy, 95–100%, when performed guided though the best lateral site was SLP. Both withinstudy and between-study analyses found that guided injections,
irrespective of sites of injection, to be more accurate than blinded
injections. Overall it can be estimated that approximately one in
five blinded injections are inaccurate. Other reviews have found
similar findings with respect to accuracy of blinded vs guided
injections [45] and blinded injections at the LMP and AMJL sites
[46]. Daley et al. [1] pooled seven papers evaluating three knee
injection sites and a total of 429 injections but excluded trials
investigating accuracy of IAKIs performed on cadaveric knees. Our
review included more papers that have been published since then,
pooling results from 22 studies, evaluating accuracy of eight
injection sites, and totaling 2735 knee injections. Herman [46]
though, who included cadaveric samples, found a lower accuracy
for the MMP [56% (95% CI 45–66)] and ALJL sites [67% (95% CI
43–91)] but higher accuracy for the SLP [91% (95% CI 84–99)] and
SMP sites [93% (95% CI 81–98)]. The reason for the differences in
values could be due to the smaller number of publications available
at the time of their review and unlike Hermans [46], our review
grouped injections performed over the lateral joint line as ALJL
irrespective of the degree of flexion or extension of the knees.
In this review, guided injections were undertaken primarily using
ultrasound. Only three of the 15 publications that evaluated accuracy
of IAKIs used other guided techniques such as air-arthrography [13]
and fluoroscopy [20,38]. When analysis of accuracy of IAKIs was
assessed for ultrasound-guided injections only, accuracy of all sites
remained the same with the exception of the ALJL site where
accuracy reduced slightly to 97%. The SMP site has not been
evaluated for accuracy, perhaps reflecting the difficulty of the ultrasound technique when performed over the medial aspect of the knee.
In two studies, ultrasound was used to both guide and assess
accuracy. In one, confirmation of accuracy was determined by the
appearance of an injected volume of air (air bubble) within the
knee joint on the ultrasound image [19]. A limitation of this
method though is that the evidence of placement lasts only a
few seconds as the air bubbles soon dissolve and disappear. The
other trial did not describe how accuracy was determined [28].
Table 2
Accuracy of blinded and guided knee injections
Blinded knee approach: accuracy, no. out of total (%)
Lead author
Medial injections
AMJL
MMP
Guided knee approach: accuracy, no. out of total (%)
Lateral injections
SMP
ALJL
Unknown
LMP
SLP
Balint et al. [34]
Bliddal [13]
MMP
ALJL
SMP
LMP
Unknown
SLP
4/10 (40)
18/19 (95)
56/56
(100)
41/49
(84)
48/50 (96)
74/76 (97)
27/33 (82)
32/35 (91)
40/40 (100)
31/40 (78)
57/78 (73)
44/78 (56)
66/78 (85)
58/78 (74)
20/20 (100)
34/44 (77)
43/45
(96)
60/80 (75)
57/80 (71)
74/80 (93)
39/59 (66)
37/37 (100)
32/33 (97)
298/368
(81)
368/368
(100)
Park et al. [39]
30/40
(75)
41/43
(95)
43/43
(100)
Qvistgaard et al. [19]
184/184
(100)
Shah and Wright [33]
4/4
(100)
Sibbitt et al. [40]
Toda and Tsukimura
[29]
Waddell et al. [20]
18/22
(82)
74/100 (74)
42/42 (100)
35/50 (70)
20/20
(100)
Wiler et al. [30]
Wind and Smolinski
[22]
SUBTOTAL
TOTAL
GRAND TOTAL
LSB
N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
Jackson et al. [15]
Jones et al. [4]
Lopes et al. [31]
Luc et al. [32]
Myung et al. [38]
IFP
Lateral injections
51/56 (91)
Bum Park et al. [35]
Chavez-Chiang et al.
[28]
Cunnington et al. [2]
Curtiss et al. [36]
Esenyel et al. [21]
Glattes et al. [14]
Im et al. [37]
LSB
Medial injections
25/27 (93)
40/43 (93)
191/258
(74)
78/122
338/411
(64)
(82)
607/791 (77)
19/44 (43)
142/202
(70)
37/39
(95)
39/44 (89)
132/158
(84)
225/260
(87)
562/695 (81)
1284/1635 (79)
59/71
(83)
4/4
(100)
115/149
(77)
115/149
(77)
73/85
368/368
(86)
(100)
441/453 (97)
94/96 (98) 41/43
99/99
(95)
(100)
598/608 (98)
364/370
(98)
37/39
(95)
37/39
(95)
1076/1100 (98)
Abbreviations: AMJL, anteromedial joint line; MMP, medial midpatellar; SMP, superomedial patellar; ALJL, anterolateral joint line; LMP, lateral midpatellar; SLP, superolateral patellar; LSB, lateral suprapatellar bursa; IFP,
infrapatellar.
201
202
N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
Table 3
Accuracy of knee injection: influence of site and image-guidance—Relative and absolute risk difference*
Knee injection site
Medial midpatellar (guided vs blind)
Superomedial patellar (guided vs blind)
Anterolateral joint line (guided vs blind)
Lateral midpatellar (guided vs blind)
Superolateral patellar (guided vs blind)
Lateral suprapatellar bursa (guided vs blind)
Medial knee injections as a group (guided vs blind)
Lateral knee injections as a group (guided vs blind)
Guided vs Blinded injections as a group
Blinded knee injections: lateral vs medial as a group
Guided knee injections: lateral vs medial as a group
Relative risk
(95% confidence Interval)
Absolute risk difference
(95% confidence interval)
Chi squared2, p-value
1.34 (1.15–1.57)
0.22
0.18
0.28
0.12
0.13
0.15
0.21
0.17
0.19
0.04
0.01
12.17, p ¼ 0.0005
72.03, p o 0.0001
30.03, p o 0.0001
3.91, p ¼ 0.05
14.73, p ¼ 0.0001
35.44, p o 0.0001
92.13, p o 0.0001
101.48, p o 0.0001
124.54, p o 0.0001
3.75, p ¼ 0.05
1.29, p ¼ 0.3
1.22
1.39
1.14
1.15
1.18
(1.16–1.27)
(1.27–1.53)
(1.04–1.26)
(1.10–1.21)
(1.07–1.32)
1.27
1.22
1.24
1.05
1.01
(1.21–1.32)
(1.17–1.26)
(1.21–1.27)
(1.00–1.12)
(0.99–1.03)
(0.10–0.33)
(0.14–0.22)
(0.20–0.35)
(0.001–0.20)
(0.10–0.18)
(0.08–0.26)
(0.17–0.24)
(0.14–0.20)
(0.17–0.21)
(0.00–0.08)
( 0.01 to 0.03)
n
Relative risk is the proportionate difference in accuracy of injections (between groups as defined in each row) while absolute risk difference is the absolute difference in
accuracy.
The exclusion of these two studies from the analysis did not,
however, affect the results.
Few studies identified in this review attempted to correlate
accuracy of knee injection with treatment outcome. Indeed there
was only one trial on knee OA; this trial reported better outcome
for accurate injections when compared to inaccurate IAKIs [29].
Two other studies [2,4] evaluated outcomes of accurate IAKIs
together with outcomes from other joints injections (including
shoulder, elbow, wrist, ankle, finger, and acromioclavicular joints)
making it difficult to assess outcome specifically at the knee joint.
Accuracy of injection varies at different joint sites and for studies
that pooled data across many joints, it might have been more
informative if treatment outcome was reported by joint [2,4,47].
For trials that used a mixed sample of OA and RA such as that by
Sibbitt et al. [40], it would have been helpful also if the therapeutic response in the OA group was presented separately from
the RA group as it is possible that disease type may have
influenced outcome. In a separate trial, compared to those whose
injections were targeted within the joint, there was no difference
in outcome in those where the injection was delivered extraarticularly [48].
There were also only two studies that compared outcome
between different knee injection sites but found no difference
between those sites [28,33], that is, between LMP and ALJL [28]
and IFP and medial knee injections [33], though in the latter study
the IFP site was associated with less frequent joint aspiration and
worse patients' perceived improvement [33].
For outcome relating to IAKIs, the best studied issue has been a
comparison of outcomes of ultrasound-guided vs blinded injections, though accuracy of these injections was not assessed. From
the few studies, ultrasound-guided injections resulted in better
aspiration [40] and short-term therapeutic benefit than blinded
IAKIs [40,41].
There are a number of limitations to be considered when
interpreting the results of this review. First, there were relatively
few studies that permitted within-study analyses of the accuracy of
blinded vs guided injections. There was, however, little evidence of
statistical heterogeneity of the pooled studies suggesting a low risk
of bias. Second, we included studies investigating the accuracy of
IAKIs performed on cadavers [21,36] where it may be argued that
altered tissue properties could affect the outcome (accuracy of
injection). However, the use of knee dissections to verify accurate
placement of injected materials provide direct evidence in contrast
to relying on interpretation of the spread of contrast material on
radiographs during imaging to deduce intra-articular placement. We
analyzed our data by including and excluding cadaveric studies and
found accuracy for SLP and LSB to be comparable while for ALJL and
LMP to be slightly higher if the cadaveric studies were excluded.
Third, it is possible that accuracy of injection sites could also be
influenced by the method of assessment of injection accuracy
Fig. 4. Forest plot—Outcome of guided vs blinded knee injections.
N. Maricar et al. / Seminars in Arthritis and Rheumatism 43 (2013) 195–203
(including observer variability), though generally there was a trend
for greater accuracy irrespective of the assessment method.
Conclusion
Blinded IAKIs can be performed with reasonably good accuracy,
though accuracy does vary by injection site and is improved with
needle-guidance. Injectors' experience may influence the accuracy
of blinded injections. Further studies are required to address the
question whether accurate localization is linked with an improved
clinical outcome.
Acknowledgments
The Research into Osteoarthritis in Manchester (ROAM)
research team Arthritis Research UK
Appendix A.
Supplementary Information
Supplementary data associated with this article can be found in
the online version at http://dx.doi.org/10.1016/j.semarthrit.2013.
04.010.
References
[1] Daley EL, Bajaj S, Bisson LJ, Cole BJ. Improving injection accuracy of the elbow,
knee, and shoulder: does injection site and imaging make a difference?
A systematic review Am J Sports Med 2011;39:656–62.
[2] Cunnington J, Marshall N, Hide G, Bracewell C, Isaacs J, Platt P, et al.
A randomized, double-blind, controlled study of ultrasound-guided corticosteroid injection into the joint of patients with inflammatory arthritis.
Arthritis Rheum 2010;62:1862–9.
[3] Gnanadesigan N, Smith RL. Knee pain: osteoarthritis or anserine bursitis? J Am
Med Dir Assoc 2003;4:164–6.
[4] Jones A, Regan M, Ledingham J, Pattrick M, Manhire A, Doherty M. Importance
of placement of intra-articular steroid injections. BMJ 1993;307:1329–30.
[5] Courtney P, Doherty M. Joint aspiration and injection and synovial fluid
analysis. Best Pract Res Clin Rheumatol 2009;23:161–92.
[6] Lockman LE. Practice tips. Knee joint injections and aspirations: the triangle
technique. Can Fam Physician 2006;52:1403–4.
[7] Zuber TJ. Knee joint aspiration and injection. Am Fam Physician 2002;66:
1497–507.
[8] Esenyel CZ, Esenyel M, Yesiltepe R, Ayanoglu S, Bulbul M, Sirvanci M, et al. The
correlation between the accuracy of steroid injections and subsequent
shoulder pain and function in subacromial impingement syndrome. Acta
Orthop Traumatol Turc 2003;37:41–5.
[9] Eustace JA, Brophy DP, Gibney RP, Bresnihan B, FitzGerald O. Comparison of
the accuracy of steroid placement with clinical outcome in patients with
shoulder symptoms. Ann Rheum Dis 1997;56:59–63.
[10] Partington PF, Broome GH. Diagnostic injection around the shoulder: hit and
miss? A cadaveric study of injection accuracy. J Shoulder Elbow Surg 1998;7:
147–50.
[11] Souza PM, Aguiar RO, Marchiori E, Bardoe SA. Arthrography of the shoulder: a
modified ultrasound guided technique of joint injection at the rotator interval.
Eur J Radiol 2010;74:e29–32.
[12] Yamakado K. The targeting accuracy of subacromial injection to the shoulder:
an arthrographic evaluation. Arthroscopy 2002;18:887–91.
[13] Bliddal H. Placement of intra-articular injections verified by mini airarthrography. Ann Rheum Dis 1999;58:641–3.
[14] Glattes RC, Spindler KP, Blanchard GM, Rohmiller MT, McCarty EC, Block JA.
Simple, accurate method to confirm placement of intra-articular knee injection. Am J Sports Med 2004;32:1029–31.
[15] Jackson DW, Evans NA, Thomas BM. Accuracy of needle placement into the
intra-articular space of the knee. J Bone Joint Surg Am 2002;84:1522–7.
[16] Di SL, Paoloni M, Ioppolo F, Dimaggio M, Di RS, Santilli V. Ultrasound-guided
aspiration and corticosteroid injection of Baker's, cysts in knee osteoarthritis:
a prospective observational study. Am J Phys Med Rehabil 2010;89:970–5.
[17] Hurdle MF. In: Narouze SN, editor. Ultrasound-guided knee injections atlas of
ultrasound-guided procedures in interventional pain management. New York:
Springer; 2011. p. 331–4.
[18] Tarhan S, Unlu Z. Magnetic resonance imaging and ultrasonographic evaluation of the patients with knee osteoarthritis: a comparative study. Clin
Rheumatol 2003;22:181–8.
203
[19] Qvistgaard E, Kristoffersen H, Terslev L, Danneskiold-Samsoe B, Torp-Pedersen
S, Bliddal H. Guidance by ultrasound of intra-articular injections in the knee
and hip joints. Osteoarthritis Cartilage 2001;9:512–7.
[20] Waddell D, Estey D, Bricker DC, Marsala A. Viscosupplementation under
fluoroscopic control. Am J Med Sports 2001;3:237–41.
[21] Esenyel C, Demirhan M, Esenyel M, Sonmez M, Kahraman S, Sinel B, et al.
Comparison of four different intra-articular injection sites in the knee: a
cadaver study. Knee Surg Sports Traumatol Arthrosc 2007;15:573–7.
[22] Wind WM Jr., Smolinski RJ. Reliability of common knee injection sites with
low-volume injections. J Arthroplasty 2004;19:858–61.
[23] Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of
randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12.
[24] Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical Evidence of Bias. J Am
Med Assoc 1995;273:408–12.
[25] von EE, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The
Strengthening the Reporting of Observational Studies in Epidemiology
(STROBE) statement: guidelines for reporting observational studies. J Clin
Epidemiol 2008;61:344–9.
[26] Vandenbroucke JP, Ev Elm, Altman DG, Gotzsche PC, Mulrow CD, Pocock
SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Ann Intern Med
2007;147:573–7.
[27] Des J, Lyles C, Crepaz N. Improving the reporting quality of nonrandomized
evaluations of behavioral and public health interventions: the TREND statement. Am J Public Health 2004;94:361–6.
[28] Chavez-Chiang CE, Sibbitt WL Jr., Band PA, Chavez-Chiang NR, Delea SL,
Bankhurst AD. The highly accurate anteriolateral portal for injecting the knee.
Sports Med Arthrosc Rehabil Ther Technol 2011;3:6.
[29] Toda Y, Tsukimura N. A comparison of intra-articular hyaluronan injection
accuracy rates between three approaches based on radiographic severity of
knee osteoarthritis. Osteoarthritis Cartilage 2008;16:980–5.
[30] Wiler JL, Costantino TG, Filippone L, Satz W. Comparison of ultrasound-guided
and standard landmark techniques for knee arthrocentesis. J Emerg Med
2010;39:76–82.
[31] Lopes RV, Furtado RNV, Parmigiani L, Rosenfeld A, Fernandes ARC, Natour J.
Accuracy of intra-articular injections in peripheral joints performed blindly in
patients with rheumatoid arthritis. Rheumatology (Oxford) 2008;47:1792–4.
[32] Luc M, Pham T, Chagnaud C, Lafforgue P, Legre V. Placement of intra-articular
injection verified by the backflow technique. Osteoarthritis Cartilage
2006;14:714–6.
[33] Shah KD, Wright V. Intra-articular hydrocortisone in osteo-arthrosis. Ann
Rheum Dis 1967;26:316–8.
[34] Balint PV, Kane D, Hunter J, McInnes IB, Field M, Sturrock RD. Ultrasound
guided versus conventional joint and soft tissue fluid aspiration in rheumatology practice: a pilot study. J Rheumatol 2002;29:2209–13.
[35] Bum Park Y, Ah Choi W, Kim YK, Chul Lee S, Hae Lee J. Accuracy of blind versus
ultrasound-guided suprapatellar bursal injection. J Clin Ultrasound 2012;40:20–5.
[36] Curtiss HM, Finnoff JT, Peck E, Hollman J, Muir J, Smith J. Accuracy of
ultrasound-guided and palpation-guided knee injections by an experienced
and less-experienced injector using a superolateral approach: a cadaveric
study. PM R 2011;3:507–15.
[37] Im SH, Lee SC, Park YB, Cho SR, Kim JC. Feasibility of sonography for intraarticular injections in the knee through a medial patellar portal. J Ultrasound
Med 2009;28:1465–70.
[38] Myung JS, Lee JW, Lee JY, et al. Usefulness of fluoroscopy-guided intraarticular injection of the knee. J Korean Radiol Soc 2007;56:563–7.
[39] Park Y, Lee SC, Nam HS, Lee J, Nam SH. Comparison of sonographically guided
intra-articular injections at 3 different sites of the knee. J Ultrasound Med
2011;30:1669–76.
[40] Sibbitt W, Kettwich L, Band P, Chavez-Chiang N, Delea S, Haseler LJ, et al. Does
ultrasound guidance improve the outcomes of arthrocentesis and corticosteroid injection of the knee? Scand J Rheumatol 2012;41:66–72.
[41] Sibbitt WL Jr., Band PA, Kettwich LG, Chavez-Chiang NR, Delea SL, Bankhurst
AD. A randomized controlled trial evaluating the cost-effectiveness of sonographic guidance for intra-articular injection of the osteoarthritic knee. J Clin
Rheumatol 2011;17:409–15.
[42] Moher D, Pham B, Jones A, et al. Does quality of reports of randomised trials
affect estimates of intervention efficacy reported in meta-analyses? Lancet
1998;352:609–13.
[43] Roberts NW, Hayes CW, Breitbach SA, Owen J. Dry taps and what to do about
them: a pictorial essay on failed arthrocentesis of the knee. Am J Med
1996;100:461–4.
[44] Schumacher HR. Aspiration and injection therapies for joints. Arthritis Rheum
2003;49:413–20.
[45] Daley EL, Bajaj S, Bisson LJ, Cole BJ. Improving injection accuracy of the elbow,
knee, and shoulder: does injection site and imaging make a difference?
A systematic review Am J Sports Med 2011:39.
[46] Hermans J, Bierma-Zeinstra SM, Bos PK, Verhaar JA, Reijman M. The most
accurate approach for intra-articular needle placement in the knee joint:
a systematic review. [Review]. Semin Arthritis Rheum 2011;41:106–15.
[47] Sibbitt WL, Band PA, Chavez-Chiang NR, Delea SL, Norton HE, Bankhurst ADA.
Randomized controlled trial of the cost-effectiveness of ultrasound-guided
intraarticular injection of inflammatory arthritis. J Rheumatol 2011;38:252–63.
[48] Sambrook PN, Champion GD, Browne CD, Cairns D, Cohen ML, Ray RO, et al.
Corticosteroid injection for osteoarthritis of the knee: peripatellar compared
to intra-articular route. Clin Exp Rheumatol 1989;7:609–13.