British Journal of Anaesthesia, 116 (5): 597–609 (2016)

doi: 10.1093/bja/aew099
Review Article

The analgesic efficacy of local infiltration analgesia

vs femoral nerve block after total knee arthroplasty:
a systematic review and meta-analysis
E. Albrecht1,*, O. Guyen2, A. Jacot-Guillarmod3 and K. R. Kirkham4
1
Department of Anaesthesia, 2Department of Orthopaedic surgery, 3Department of Anaesthesia, Lausanne
University Hospital, Lausanne, Switzerland, and 4Department of Anaesthesia, Toronto Western Hospital,
University of Toronto, Toronto, Canada
*Corresponding author. E-mail: eric.albrecht@chuv.ch

Abstract
Many consider femoral nerve block the gold standard in pain management following knee arthroplasty. Local infiltration
analgesia is an alternate approach that applies the concept of surgical wound infiltration with local anaesthetics. This meta-
analysis aims to compare both analgesic treatments for analgesia and functional outcomes after total knee arthroplasty.
This meta-analysis was performed according to the PRISMA statement guidelines. The primary outcomes were cumulative
i.v. morphine consumption, pain scores at rest and on movement on postoperative day one (analogue scale,0–10). Secondary
outcomes included range of motion, quadriceps muscle strength, length of stay and rates of complications (neurologic events,
cardiovascular events, falls and knee infections). Fourteen trials, including 1122 adult patients were identified. There was no
difference in i.v. morphine consumption (mean difference: −2.0 mg; 95% CI: −4.9, 0.9 mg; I 2=69%; P=0.19), pain scores at rest
(mean difference: −0.1; 95% CI: −0.4, 0.3; I 2=72%; P=0.80) and pain scores on movement (mean difference: 0.2; 95% CI: −0.5, 0.8;
I 2=80%; P=0.64) on postoperative day one (a negative mean difference favours local infiltration analgesia). The qualities of
evidence for our primary outcomes were moderate according to the GRADE system. There were no clinical differences in
functional outcomes or rates of complications. Complication rates were captured by three trials or fewer with exception of
knee infection, which was sought by eight trials. Local infiltration analgesia provides similar postoperative analgesia after total
knee arthroplasty to femoral nerve block. Although this meta-analysis did not capture any difference in rates of complications,
the low number of trials that specifically sought these outcomes dictates caution.

Key words: analgesia; nerve block; postoperative pain; regional anaesthesia; total knee arthroplasty

Total knee arthroplasty (TKA) causes moderate to severe post-
surgical pain, 1 with femoral nerve block (FNB) considered
by many as the gold standard analgesic therapy after this
surgery.2–5
Local infiltration analgesia (LIA) applies the concept of surgi-
cal wound infiltration with local anaesthetics6 7 to joint surgery.8
The technique was first reported for knee arthroplasty by Bianco-
ni and colleagues9 fewer than 15 years ago. Since then, it has
gained widespread popularity among orthopaedic surgeons be-
cause of its ease of application, cost effectiveness and lack of ap-
parent motor block of the lower limb.10 11 The initial enthusiasm
prompted a number of randomized controlled trials comparing
LIA with FNB, which reported conflicting results for analgesic ef-
ficacy.12–14 Several systematic reviews have endeavoured to clar-
ify the magnitude of analgesic effect of both procedures, but their
results are limited by the absence of quantitative meta-analysis

Accepted: March 1, 2016

© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
For Permissions, please email: journals.permissions@oup.com

597
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 598 | Albrecht et al.
assessment,15–18 the fact that they do not address this question
directly,19 or did not investigate the relative benefit of each inter-
vention on functional recovery.20
This meta-analysis aims to compare the analgesic efficacy,
the functional outcomes and the technique-related complica-
tions of FNB and LIA after TKA in adult patients.
Methods
Literature search and inclusion criteria
The authors applied the recommendations of the ‘Preferred Re-
porting Items for Systematic Reviews and Meta-Analyses’ (PRIS-
MA) statement.21 The electronic databases MEDLINE (until
February 2016), the Cochrane Central Register of Controlled Clin-
ical Trials (until February 2016), and the Excerpta Medica data-
base, EMBASE (until February 2016) were searched with the
following terms: Knee joint OR Knee surgery OR Total knee re-
placement OR Total knee arthroplasty. These search results
were associated with Local infiltration analgesia OR Periarticular
infiltration OR Peri-articular infiltration OR Periarticular injection
OR Peri-articular injection OR Intraarticular infiltration OR Intra-
articular infiltration OR Intraarticular injection OR Intra-articular
injection OR Intraarticular analgesia OR Intra-articular analgesia.
Findings were further restricted by associating with Regional an-
aesthesia OR Regional anesthesia OR Anaesthetic technique OR
Anesthetic technique OR Anaesthesia conduction OR Anesthesia
conduction OR Local anaesthetics OR Local anesthetics OR Nerve
block OR Peripheral nerve block OR Femoral nerve block OR
Adductor canal block OR Saphenous nerve block. The following
keywords were also searched: Anaesth*, Anesth*, Nerve*, Re-
placement*, Arthroplasty*. Search results were limited to rando-
mized controlled trials and humans. No language restriction was
placed on the search. Lastly, bibliographies of retrieved articles
were scrutinized for any relevant trials not yet identified in the
primary search.
Population
The meta-analysis addresses male or female adults undergoing
TKA.
Intervention and comparator
Only randomized trials comparing LIA to a group of patients hav-
ing single-shot or continuous femoral nerve, saphenous nerve, or
adductor canal blocks were included in the present meta-ana-
lysis. Any article that applied the LIA technique described by
Kerr and Kohan,11 in total or in part to a group (infiltration of
any layer of the knee joint: posterior part, anterior part, peri-
articular soft tissue), was included. We excluded trials comparing
LIA with a combination of epidural analgesia and FNB22–24 or in-
vestigating the analgesic efficacy of the combination of LIA and
FNB with the combination of sciatic nerve block and FNB.25–27
Outcomes
The specific outcomes sought from each article were derived fol-
lowing our approach described in a previous meta-analysis on
acute postoperative pain.28 The primary acute pain-related out-
comes were cumulative i.v. morphine consumption, and pain
scores at rest and on movement on postoperative day one (24
postoperative h). Secondary acute pain-related outcomes sought
were cumulative i.v. morphine consumption at two and 12 post-
operative h, and on postoperative day two and three; pain scores
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at rest and on movement measured at two and 12 postoperative h,
and on postoperative day two and three; incidences of post-
operative nausea or vomiting, pruritus within the first 24 h post-
operatively, and chronic postoperative pain. Additional functional
outcomes evaluated were range of motion or knee flexion on post-
operative days one, two and three; quadriceps muscle strength on
postoperative days one, two and three; Knee Society score29 at six
weeks, three and 12 months postoperatively; and length of stay.
We also aimed to capture any analgesic technique-related compli-
cation, such as rates of neurologic events, cardiovascular events,
falls, knee joint infections, prosthesis loosening, or revision surgery.
Finally, local anaesthetic plasma concentrations were retrieved
whenever possible.
Trial characteristics
Extracted trial characteristics included type (single-shot injection
or catheter insertion) and technique of LIA and peripheral nerve
block, respectively; type, concentration and volume of local anaes-
thetics; type of other components used; anaesthetic strategy for
surgery, and type and modality of postoperative analgesia.
Rating of the studies
The quality of the research methodology of each randomized trial
was assessed following the Cochrane Collaboration’s Risk of Bias
Tool for randomized controlled trials.30 Two authors (A.J.G. and
K.K.) separately screened, reviewed and rated the items for each
trial using this method and extracted data for the analyses. Dis-
agreements with scoring or extracted data were addressed after
discussion with a third author (E.A.).
Data extraction
Means, standard deviation, standard error of means, 95% confi-
dence interval (CI), number of events and total number of partici-
pants were extracted from the text, tables or graphs from each
source study. The authors of trials that failed to report the sample
size or results as a mean and standard deviation, or standard
error of the mean, or 95% CI, were contacted twice by email to re-
quest the missing data or raw data. If no response was obtained,
median and interquartile range were used for means and stand-
ard deviation approximation, as follows: the mean was estimated
as equivalent to the median and the standard deviation was ap-
proximated to be the interquartile range divided by 1.35.31 All
opioids were converted into equi-analgesic doses of i.v. mor-
phine for analysis (i.v. morphine 10 mg=oral morphine 30
mg=IV hydromorphone 1.5 mg=oral hydromorphone 7.5 mg=IV
pethidine 75 mg=oral oxycodone 20 mg=IV tramadol 100 mg).32 33
Pain scores reported as Visual, Verbal or Numeric Rating Scales
were converted to a standardized 0–10 analogue scale for quantita-
tive evaluations. Finally, we rated the quality of evidence for each
outcome following the Grades of Recommendation, Assessment,
Development, and Evaluation (GRADE) Working Group system.34
Statistical analysis
Review Manager software (RevMan version 5.3.5; Copenhagen,
The Nordic Cochrane Centre, The Cochrane Collaboration 2014)
was used to perform meta-analyses. This software estimates
the weighted mean differences for continuous data and risk
ratio for categorical data between groups. It produces an overall
estimate of the pooled effect. As most data sets were heteroge-
neous, they were analysed using a random effects model, and
are presented as the mean difference or relative risk (RR) with
 Local infiltration vs nerve block after knee replacement | 599

95%. Our primary outcomes (i.v. morphine consumption, pain
scores at rest and on movement on postoperative day one) were
analysed in subgroups according to the specialization of the cor-
responding author (anaesthetist vs orthopaedic surgeon). We
conducted a meta-analysis when two or more trials reported
similar outcomes. I 2 was used to evaluate heterogeneity. Prede-
termined thresholds were established for low (25–49%), moderate
(50–74%), and high (>75%) levels.35 Publication biases were evaluated
for our primary outcomes by drawing a funnel plot of standard
error of the mean difference (y-axis) as a function of the mean dif-
ference (x-axis) and confirmed with Duval and Tweedie’s trim
and fill test,36 performed using Comprehensive Meta-analysis
Version 2 software (Biostat, Englewood, NJ). A 2-sided
P value <0.05 was considered significant.
Results
One thousand three hundred and forty-seven citations were
identified from the literature search strategy, 14 of which met
the inclusion criteria, representing a total of 1122 patients (Fig. 1).
Table 1 presents the trial characteristics. According to our as-
sessment following the Cochrane Collaboration Risk of Bias tool
(Fig. 2), the majority of trials had a low risk of bias. Attempts
were made to contact eight authors,13 14 41 38 45 39 40 47 and two

Regional anaesthesia Knee joint Local infiltration

Regional anesthesia
Anaesthetic technique
Anesthetic technique
Anaesthesia conduction
Anesthesia conduction
Identification
Knee surgery analgesia
Knee replacement Periarticular infiltration
Knee arthroplasty Peri-articular infiltration
Replacement* as a keyword Periarticular injection
Arthroplast* as a keyword Peri-articular injection

Local anaesthetics Intraarticular infiltration

Local anesthetics
Nerve block
Peripheral nerve block
Femoral nerve block
Adductor canal block
Saphenous nerve block
Anaesth* as a keyword
Anesth* as a keyword
Nerve* as a keyword
Intra-articular infiltration
Intraarticular injection
Intra-articular injection
Intraarticular analgesia
AND
Intra-articular analgesia
1347 citations

Did not meet inclusion

criteria after title review
Screening

91 abstracts

Did not meet inclusion

criteria after abstract
review
Eligibility

16 full text
articles

Did not meet inclusion

criteria after article
review

0 articles retrieved from

14 full text scanning bibliographies
articles
Included

14 full text
articles

Fig. 1 PRISMA flow diagram showing literature search results. Fourteen randomized controlled trials were included in the analysis.

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 600
Table 1 Trial characteristics

| Albrecht et al.
Reference Group (n) Local infiltration analgesia Femoral nerve block Anaesthetic Postoperative analgesia Primary outcome Comments
Solution Technique Solution Technique strategy

Single-shot injection
Ashraf and Local infiltration Ropivacaine 0.2% 150 ml, Infiltration into all layers Ropivacaine 0.2% Ultrasound Spinal Acetaminophen, Pain scores at 4 -
colleagues, analgesia ketorolac 30 mg, of the knee joint 30 ml anaesthesia undefined non- postoperative h
201312 (19), epinephrine 1 mg (total during the surgery (bupivacaine steroidal anti-
Femoral nerve volume 152 ml) (posterior part, without inflammatory
block (21) anterior part, opiate) drugs, i.v. patient-
periarticular soft controlled analgesia
tissue) of morphine,
oxycodone
Fan and Local infiltration Ropivacaine 1% 10 ml, Infiltration into all layers Ropivacaine 0.5% Ultrasound General Parecoxib, i.v. patient- Not specified -
colleagues, analgesia morphine sulphate of the knee joint 20 ml combined anaesthesia controlled analgesia
201537 (79), 10 mg, betamethasone during the surgery with nerve (not detailed) of morphine
Femoral nerve 5 mg, normal saline ( posterior part, stimulation
block (78) 38 ml (total volume anterior part,
50 ml) periarticular soft
tissue)
Moghtadaei Local infiltration Ropivacaine 1% 30 ml, Infiltration into all layers Ropivacaine 1% Nerve Spinal Acetaminophen, Morphine -
and analgesia ketorolac 30 mg, of the knee joint 20 ml stimulation anesthesia ibuprofen, i.v. consumption
colleagues, (18), epinephrine 0.5 mg, during the surgery (bupivacaine morphine between 24
201438 Femoral nerve normal saline 118.5 ml ( posterior part, without and 48
block (18) (total volume 150 ml) anterior part, opiate) postoperative h
periarticular soft
tissue)
Parvataneni Local infiltration Bupivacaine 0.5% 40–80 ml, Infiltration into all layers Not specified Not specified Spinal Acetaminophen, Not specified -
and analgesia morphine sulfate 4–10 of the knee joint anesthesia celecoxib, ketorolac,
colleagues, (31), mg, epinephrine 0.3 mg, during the surgery (not detailed) oxycodone, i.v.
200739 Femoral nerve methylprednisolone ( posterior part, morphine
block (29) acetate 40 mg, anterior part,
cefuroxime 750 mg, periarticular soft
normal saline 22 ml tissue)
(total volume 73.7–114.3
ml)
Uesugi and Local infiltration Ropivacaine 0.75% 20 ml, Infiltration into the Ropivacaine 0.75% Nerve Spinal Diclofenac Pain scores in the A sciatic nerve block
colleagues, analgesia morphine 10 mg (male) posterior part of the 20 ml stimulation anesthesia postoperative was performed
201440 (100), or 5 mg (female), capsule (20 ml) and (bupivacaine period (time in patients
Femoral nerve epinephrine 0.3 mg, the periarticular soft without period not allocated to
block (100) dexamethasone 3.3 mg, tissue (22–24 ml) opiate) specified) femoral nerve
normal saline 20 ml block with
(total volume 42–44 ml) ropivacaine
0.75% 10 ml.
Continuous infusion and iterative injections
Affas and Local infiltration Ropivacaine 0.2% 150 ml, 30 ml intracutaneously Ropivacaine 0.2% Nerve Spinal Acetaminophen, i.v. Pain scores on Patients with a
colleagues, analgesia ketorolac 30 mg, before incision, 80 ml 30 ml, followed stimulation anaesthesia patient-controlled movement femoral nerve
201141 (20), epinephrine 0.5 mg in the posterior part by 15 ml every (bupivacaine analgesia of at 24 block received i.
Femoral nerve (total volume 156 ml) of the capsule and 4h for 24 h without morphine postoperative h v. ketorolac
block (20) 46 ml infused opiate) 10 mg every 8h
through an intra- for 24 h (total
articular catheter dose 30 mg).
placed at the end of
the surgery for 24 h

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 Carli and Local infiltration Ropivacaine 0.2% 100 ml, Infiltration into the Ropivacaine 0.2% Nerve Spinal Acetaminophen, Cumulative All patients received
colleagues, analgesia ketorolac 30 mg, posterior part of the 8 ml followed by stimulation anaesthesia celecoxib, i.v. morphine an infiltration of
201013 (20), epinephrine 0.5 mg capsule (see an infusion of (bupivacaine patient-controlled consumption the posterior
Femoral nerve (total volume 101.5 ml) comments). Second ropivacaine 0.2% without analgesia of at 48 capsule of the
block (20) injection through an 8 ml/h for 48h opiate) morphine, postoperative h knee with
intra-articular oxycodone ropivacaine
catheter at 24 0.2% 50 ml,
postoperative h of ketorolac 30 mg
an infusion of and
Ropivacaine 0.5% epinephrine
50 ml, ketorolac 0.25 mg.
30 mg, epinephrine Justification
0.25 mg (total was to cover
volume 51.25 ml) popliteal pain
(total volume
51.25 ml).
Chaumeron Local infiltration Ropivacaine 0.2% 150 ml, Infiltration into the Ropivacaine 0.25% Nerve Spinal Acetaminophen, Cumulative -
and analgesia ropivacaine 1% 10 ml, posterior part of the 20 ml, followed stimulation anaesthesia celecoxib, i.v. morphine
colleagues, (29), ketorolac 30 mg, capsule and the by an infusion of (bupivacaine patient-controlled consumption
201314 Femoral nerve epinephrine 0.5 mg periarticular soft ropivacaine 0.2% without analgesia of at 48
block (30) (total volume 161.5 ml) tissue. Second 8 to 10 ml/h for opiate) morphine for 48 h postoperative h
injection of 48 to 72 h followed by oral
ropivacaine 1% 15 narcotics
ml through an intra- (hydromorphone,
articular catheter codeine,
between 16 and 24 oxycodone)
postoperative h

Local infiltration vs nerve block after knee replacement

Kovalak and Local infiltration Levobupivacaine 0.25% Infiltration into all layers Levobupivacaine Ultrasound Spinal Acetaminophen, Not specified Patients with local
colleagues, analgesia 75 ml, epinephrine of the knee joint 0.25% 10 ml combined anaesthesia dexketoprofen, i.v. infiltration
42
2015 (29), 0.75 mg (total volume during the surgery followed by an with nerve (not patient-controlled analgesia had a
Femoral nerve 75 ml) ( posterior part, infusion of stimulation detailed) analgesia of single injection
block (30) anterior part, levobupivacaine tramadol for 24 h during the
periarticular soft 8 ml/h for 24 h followed by oral surgery only.
tissue) tramadol
Kurosaka Local infiltration Ropivacaine 0.75% 40 ml, Infiltration into all layers Ropivacaine 0.2% 20 Ultrasound General Loxoprofen, i.v. patient- Pain scores at 24 Patients with local
and analgesia ketoprofen 100 mg, of the knee joint ml followed by anaesthesia controlled analgesia postoperative h infiltration
colleagues, (21), epinephrine 0.5 mg, during the surgery an infusion of (not of morphine analgesia had a
43
2016 Femoral nerve normal saline 40 ml ( posterior part, ropivacaine detailed) single injection
block (21) (total volume 85 ml) anterior part, 0.15% 5 ml/h for during the
periarticular soft 48 h) surgery only.
tissue)
Kutzner and Local infiltration Ropivacaine 0.75% 50 ml, Continuous infusion Continuous infusion Not specified General Acetaminophen, Pain scores at 24 -
colleagues, analgesia morphine sulphate 2 through a catheter of ropivacaine anaesthesia etoricoxib, oral postoperative h
201544 (60), mg, normal saline 148 positioned below 0.2% at a rate of 8 (not oxycodone or
Femoral nerve ml (total volume 350 ml) the fascia at a rate of ml/h for 48 h (no detailed) intramuscular
block (60) 8 ml/h for 44 h (no initial bolus piritramide
preliminary injection)
infiltration)

Continued

| 601
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 Table 1 Continued

602
Reference Group (n) Local infiltration analgesia Femoral nerve block Anaesthetic Postoperative analgesia Primary outcome Comments

| Albrecht et al.
Solution Technique Solution Technique strategy

Ng and Local infiltration Ropivacaine 1% 30 ml, Infiltration into all layers Ropivacaine 0.2% Nerve General i.v. patient-controlled Cumulative Patients with local
colleagues, analgesia epinephrine 1 mg, of the knee joint 20 ml followed stimulation anaesthesia analgesia of morphine infiltration
201245 (16), triamcinolone during the surgery by an infusion of with morphine consumption analgesia had a
Femoral nerve acetonide 40 mg, ( posterior part, 10 ml/h for 72 h remifentanil at 72 single injection
block (16) normal saline 70 ml anterior part, postoperative h during the
(total volume 101,5 ml) periarticular soft surgery only.
tissue)
Spangehl Local infiltration Ropivacaine 0.5% 40–80 ml, Infiltration into all layers Ropivacaine 0.5% Nerve General Acetaminophen, Pain scores at 24 Patients with local
and analgesia ketorolac 30 mg, of the knee joint 30 ml followed stimulation anaesthesia diclofenac, postoperative h infiltration
colleagues, (81), epinephrine 0.1–0.3 mg, during the surgery by an infusion of or (not gabapentine, i.v. analgesia had a
201546 Femoral nerve morphine sulphate ( posterior part, ropivacaine 0.2% ultrasound detailed) hydromorphone or single injection
block (79) 5 mg, normal saline up anterior part, of 6–12 ml/h for oral oxycodone during the
to a total volume of periarticular soft 48 h surgery only.
120 ml tissue).
Toftdahl and Local infiltration Ropivacaine 0.2% 150 ml, Infiltration into all layers Ropivacaine 1% Nerve Spinal Acetaminophen, Oxycodone Patients in group
colleagues, analgesia ketorolac 30 mg, of the knee joint 20 ml, followed stimulation anaesthesia ibuprofen, consumption PNB received
200747 (40), epinephrine 0.5 mg during the surgery by an infusion of (bupivacaine oxycodone, i.v. (time period bupivacaine
Femoral nerve (total volume 152 ml) ( posterior part, ropivacaine 0.2% without morphine not specified) 50 mg with
block (37) anterior part, 10 ml/h for 48h opiate) morphine 4 mg
periarticular soft with bolus of into the
tissue). Two boluses 20 ml available intraarticular
of 22 ml every 12 h every 8 h drain at the end
for 24 h were of surgery (total
injected through the volume 20 ml).
catheter
(ropivacaine 1%
20 ml, ketorolac 30
mg and epinephrine
0.5 mg)

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 Local infiltration vs nerve block after knee replacement | 603

trials,13 45 46 below 100 ml in five others37 39 40 42 43 and 350 ml

in one.44 The solution for LIA contained epinephrine combined

Blinding of participants and personnel (performance bias)

with ketoprofen43 or ketorolac in eight trials,12 13 14 38 41 46 47 com-
bined with a steroid in four trials,37 39 40 45 or with morphine in
five trials.37 39 40 44 46 Finally, in one trial the solution contained

Blinding of outcome assessment (detection bias)

Random sequence generation (selection bias)
an antibiotic.39 Ropivacaine doses for the initial injection of
FNB were 60 mg or less in most trials12–14 41–45 five trials injected

Incomplete outcome data (attrition bias)

ropivacaine 100 mg,37 150 mg40 46 or 200 mg,38 47 while one trial

Allocation concealment (selection bias)

did not specify.39

Selective reporting (reporting bias)

There were no differences in i.v. morphine consumption, pain
scores at rest or pain scores on movement on postoperative day
one (Table 2). Subgroup analysis according to the specialization
of the corresponding author (anaesthetist vs orthopaedic sur-
geon) did not reveal any difference (morphine consumption:
P=0.19; pain scores at rest on postoperative day one: P=0.80;
pain scores on movement on postoperative day one: P=0.64).

Other bias
With regards to the funnel plots for our primary outcomes,
the Duval and Tweedie’s trim and fill test revealed the point esti-
mates for the combined studies to be −0.18 (95% CI: −0.50, 0.13),
Affas et al. 2011 ref 37 + + – ? – + + −0.09 (95% CI: −0.35, 0.16), −0.28 (95% CI: −0.74, 0.18) for i.v. mor-
phine consumption, pain scores at rest, and pain scores on move-
Ashraf et al. 2013 ref 12 + + – + + + +
ment on postoperative day one, respectively. These findings
Carli et al. 2010 ref 13 + + – + + + + suggest an absence of publication bias. The qualities of evidence
for our primary outcomes were moderate according to the GRADE
Chaumeron et al. 2013 ref 14 + + + + + + +
working system.
Fan et al. 2015 ref 43 ? + + + + + + Tables 2 and 3 presents secondary acute pain-related out-
comes and functional outcomes, respectively. Based on two trials
Kovalak et al. 2015 ref 44 – + – – + + +
that specifically reported the reduction in i.v. morphine con-
Kurosaka et al. 2015 ref 45 + ? – ? + + + sumption at 12 postoperative h the difference between groups
reached statistical significance, however the clinical impact is
Kutzner et al. 2015 ref 46 – + – – + + +
questionable. Similarly, range of motion on postoperative day
Moghtadaei et al. 2014 ref 38 + ? + + + + + two, Knee Society knee score at six weeks and length of stay
were statistically different but without direct clinical relevance.
Ng et al. 2012 ref 39 + ? ? + + – +
There were no significant differences in the other secondary out-
Parvataneni et al. 2007 ref 40 ? ? – + ? + + comes. No trials aimed to capture chronic postoperative pain.
With respect to the occurrence of complications, knee infection
Spangehl et al. 2014 ref 47 + + – – + + + was sought by eight trials representing a total of 313 patients in
Toftdahl et al. 2007 ref 41 ? + – ? + + + group LIA.13 14 38–40 42 45 47 With the exception of prosthesis loosen-
ing or revision surgery that were not captured, individual compli-
Uesugi et al. 2014 ref 42 + + + + + + + cations were recorded by three or fewer trials. There were no
differences between groups in complication rates (Table 4). No
trials reported serum local anaesthetic concentration.
Fig. 2 Cochrane collaboration risk of bias summary: evaluation of bias risk
items for each included study. Blue circle, low risk of bias; green circle, high
risk of bias; pink circle, unclear risk of bias.
Discussion
This systematic review and meta-analysis evaluates the post-
operative analgesic efficacy and functional outcomes of LIA in
provided the additional data requested.13 47 Data were approxi- comparison to FNB. Based on 14 randomized controlled trials
mated from median and range in one trial,38 and were not usable and 1122 patients, our results show that both techniques are
in another,39 as neither standard deviations, confidence interval equivalent in terms of pain and functional outcomes. However,
nor percentiles were reported. higher doses of local anaesthetic are required within the LIA
Five trials compared single-shot injection techniques,12 37–40 group. Although the reported complication rate was not different
whereas nine studied continuous infusion techniques or itera- between groups, the small number of trials that specifically
tive injections.13 14 41–47 With the exception of four trials where sought to capture these outcomes limits the generalizability of
authors used ultrasound guidance12 37 42 43 and two where it this conclusion. The quality of evidence for both the primary
was not specified,39 44 all authors performed the FNB with the and secondary outcomes is moderate to very low because of in-
help of a nerve stimulator only. No trial compared LIA with a sa- consistency in absolute effects observed for all outcomes and
phenous nerve or adductor canal blocks. the limited number of trials reporting many outcomes.
The total dose of ropivacaine injected for LIA was consistently The desire to optimize care pathways for TKA is a timely issue
300 mg,12 13 14 38 41 43 45 47 except in four trials where authors ad- in many anaesthesia practices. Funding and efficiency concerns
ministered bupivacaine 200 to 400 mg,39 ropivacaine 100 mg37 or encourage the application of evidence-based techniques to im-
150 mg,40 and a continuous infusion of ropivacaine over a period prove both early and late outcomes.48 As an example, the intro-
of 44 h.44 The volumes injected for LIA varied between 150 and duction of outpatient TKA requires careful attention to the
200 ml in five trials,12 14 38 41 47 between 100 and 120 ml in three immediate postoperative issue of analgesia with a similar

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 604
Table 2 Secondary acute pain-related outcomes and opioid-related side-effects. A negative mean difference favours Local infiltration analgesia group, and a positive difference, Femoral nerve
block group. CI, confidence interval; n, number of events; N, total number of participants; , standard deviation

| Albrecht et al.
Outcomes References Group Mean difference [95% CI] I 2 (%) P value Quality of evidence
Local infiltration analgesia Femoral nerve block or Relative risk [95% CI] (GRADE)

Mean or n  N Mean or n  N

IV morphine consumption equivalent (mg)

2 postoperative h - - - - - - - - - - -
12 postoperative h Chaumeron 201314 12.5 10.7 29 18.7 11.3 30 −4.0 [−6.0, −2.0] 0 <0.0001 Very low
Toftdahl 200747 19.9 3.3 40 14.6 5.8 37
Postoperative day one Affas 201141 24.0 17.1 20 32.0 19.2 20 −2.0 [−4.9, 0.9] 69 0.19 Moderate
Carli 201013 34.9 29.0 20 21.6 21.3 20
Fan 201637 17.2 2.2 79 17.4 2.3 78
Kurosaka 201543 11.6 3.7 21 15.6 7.0 2.1
Moghtadaei 201438 10.0 3.7 18 12.5 7.4 18
Ng 201245 18.0 14.3 16 16.4 13.5 16
Spangehl 201446 49.0 29.0 81 43.0 29.0 79
Toftdahl 200747 32.1 7.4 40 38.9 11.3 37
Postoperative day two Carli 201013 59.6 47.9 20 35.6 28.3 20 −0.9 [−4.3, 2.6] 43 0.63 Low
Fan 201637 12.7 2.5 79 12.3 2.6 78
Chaumeron 201314 57.9 39.9 29 57.2 37.6 30
Moghtadaei 201438 15.0 7.4 18 15.0 8.3 18
Spangehl 201446 30.0 29.0 81 33.0 28.0 79
Toftdahl 200747 52.8 12.5 40 60.0 17.9 37
Postoperative day three Chaumeron 201314 25.9 15.2 29 15.0 31.7 30 0.8 [−3.9, 5.4] 40 0.75 Low
Fan 201637 7.9 2.4 79 7.6 2.1 78
Ng 201245 42.0 14.6 16 39.0 12.8 16
Toftdahl 200747 70.8 18.2 40 77.6 25.0 37
Pain scores at rest (analogue scale, 0–10)
two postoperative h Ashraf 201312 1.6 2.4 19 3.6 3.2 21 −0.7 [−2.4, 0.9] 88 0.39 Low
Chaumeron 201314 1.7 5.8 29 3.5 5.4 30
Moghtadaei 201438 3.0 1.5 18 4.0 1.5 18
Uesugi 201440 1.2 2.4 100 0.2 0.5 100
12 postoperative h Moghtadaei 201438 6.0 1.5 18 5.0 0.9 18 0.6 [−0.1, 1.2] 57 0.08 Very low
Uesugi 201440 0.9 1.4 100 0.6 0.9 100
Postoperative day one Affas 201141 1.6 1.5 20 2.1 1.7 20 −0.1 [−0.4, 0.3] 72 0.80 Moderate
Ashraf 201312 2.9 2.3 19 4.4 2.3 21
Carli 201013 4.0 2.7 20 2.7 2.2 20
Chaumeron 201314 1.7 2.9 29 1.7 3.2 30
Fan 201637 3.4 0.7 79 3.4 0.7 78
Kovalak 201542 3.2 2.0 28 1.9 1.4 32
Kurosaka 201543 3.4 1.0 21 4.2 1.3 21
Kutzner 201544 5.1 2.5 60 4.6 2.6 60
Moghtadaei 201438 6.0 0.7 18 6.0 0.7 18
Ng 201245 2.8 0.9 16 2.7 1.1 16
Spangehl 201446 2.8 1.8 81 2.4 1.6 79
Uesugi 201440 1.6 1.8 100 2.7 2.3 100

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 Postoperative day two Carli 201013 2.5 2.6 20 1.6 2.1 20 0.3 [−0.1, 0.5] 48 0.09 Moderate
Chaumeron 201314 1.6 6.6 29 1.2 5.0 30
Fan 201637 3.0 0.6 79 2.8 0.7 78
Kovalak 201542 1.5 1.3 28 0.4 0.7 32
Kurosaka 201543 4.0 2.0 21 4.0 1.3 21
Kutzner 201544 3.4 2.3 60 3.3 2.2 60
Ng 201245 1.6 1.0 16 1.6 1.0 16
Spangehl 201446 1.5 1.4 81 1.7 1.5 79
Uesugi 201440 2.6 2.0 100 2.4 2.0 100
Postoperative day three Chaumeron 201314 1.2 3.7 29 1.1 3.8 30 0.1 [−0.1, 0.3] 0 0.17 Low
Fan 201637 2.8 0.5 79 2.7 0.6 78
Kurosaka 201543 3.5 2.0 21 4.0 1.5 21
Kutzner 201544 2.8 2.1 60 2.6 1.8 60
Ng 201245 1.4 1.1 16 0.8 1.1 16
Pain scores on movement (analogue scale, 0–10)
two postoperative h Chaumeron 201314 2.6 4.4 29 3.7 5.25 30 −1.1 [−3.6, 1.4] - 0.38 Very low
12 postoperative h - - - - - - - - - - -
Postoperative day one Affas 201141 2.4 1.3 20 2.4 1.7 20 0.2 [−0.5, 0.8] 80 0.64 Moderate
Carli 201013 5.8 2.9 20 5.2 2.2 20
Chaumeron 201314 4.9 2.1 29 4.7 3.3 30
Fan 201637 6.9 0.5 79 7.1 0.6 78
Kovalak 201542 5.6 1.5 28 4.5 1.2 32
Ng 201245 7.3 1.0 16 6.4 1.0 16

Local infiltration vs nerve block after knee replacement

Toftdahl 200747 3.0 3.0 40 5.0 3.0 37
Postoperative day two Carli 201013 4.4 2.5 20 4.6 2.3 20 −0.1 [−0.4, 0.3] 34 0.71 Low
Chaumeron 201314 5.1 4.4 29 3.9 4.1 30
Fan 201637 6.6 0.5 79 6.5 0.6 78
Kovalak 201542 4.5 1.3 28 4.3 1.1 32
Ng 201245 5.9 1.1 16 6.6 0.8 16
Toftdahl 200747 4.0 2.2 40 4.5 3.0 37
Postoperative day three Chaumeron 201314 5.2 3.8 29 3.7 6.3 30 0.4 [−0.1, 0.8] 0 0.10 Very low
Fan 201637 7.9 2.4 79 7.6 2.1 78
Ng 201245 5.5 0.9 16 5.1 0.8 16
Postoperative nausea and vomiting
Fan 201637 21 - 79 18 - 78 1.1 [0.9, 1.3] 0 0.56 Low
Kurosaka 201543 0 - 21 0 - 21
Moghtadaei 201438 1 - 18 1 - 18
Ng 201245 0 - 16 0 - 16
Spangehl 201446 19 - 81 18 - 78
Toftdahl 200747 31 - 40 28 - 37
Uesugi 201440 12 - 100 8 - 100
Pruritus
Kurosaka 201543 0 - 21 0 - 21 0.8 [0.5, 1.2] - 0.30 Very low
Uesugi 201440 0 - 100 0 - 100
Toftdahl 200747 18 - 40 21 - 37

| 605
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| Albrecht et al.
Table 3 Functional outcomes. A negative mean difference favours Femoral nerve group, and a positive difference, Local infiltration analgesia group, except for Length of stay, where the reverse is
true. CI, confidence interval; n, number of events; N, total number of participants; , standard deviation

Outcome Reference Group Mean difference I 2 (%) P value Quality of

Local infiltration analgesia Femoral nerve block [95% CI] evidence
(GRADE)
Mean or n  N Mean or n  N

Range of motion (degrees)

Postoperative day one Carli 201013 66.2 13.4 20 70.0 19.5 20 −4.8 [−11.2, 1.6] 60 0.14 Low
Chaumeron 201314 79.0 33.2 29 76.2 30.3 30
Kovalak 201542 85.9 11.1 28 97.2 10.2 32
Kutzner 201544 32.6 13.2 60 34.0 18.0 60
Postoperative day two Carli 201013 76.0 12.3 20 78.6 8.0 20 −5.7 [−8.8, −2.6] 0 0.0004 Low
Chaumeron 201314 85.5 27.8 29 89.2 21.3 30
Kovalak 201542 91.3 10.7 28 99.4 7.6 32
Kutzner 201544 43.1 14.4 60 48.0 19.1 60
Postoperative day three Carli 201013 83.0 12.0 20 85.3 6.2 20 −4.2 [−8.5, 0.2] 9 0.06 Low
Chaumeron 201314 87.5 28.3 29 85.3 29.5 30
Kutzner 201544 55.6 16.6 60 62.9 16.8 60
Quadriceps muscle strength ( pounds)
Postoperative day one Ng 201245 2.0 0.4 16 2.2 0.2 16 −0.1 [−0.4, 0.1] - 0.19 Very low
Postoperative day two Ng 201245 2.6 0.5 16 2.7 0.2 16 −0.2 [−0.4, 0.1] - 0.23 Very low
Postoperative day three Ng 201245 2.8 0.2 16 2.8 0.2 16 0.0 [−0.2, 0.2] - 1.00 Very low
Knee Society score
six weeks Carli 201013 138.0 34.0 20 156.0 24.0 20 −8.7 [−15.9, −1.6] 22 0.02 Very low
Kovalak 201542 49.2 4.9 28 56.5 7.4 32
three months Fan 201637 86.5 3.1 79 86.8 3.2 78 −0.3 [−1.3, 0.7] 0 0.56 Very low
Ng 201245 92.0 8.3 16 92.0 8.3 16
12 months Fan 201637 93.9 3.1 79 94.2 2.6 78 −0.3 [−1.2, 0.6] 0 0.52 Very low
Ng 201245 97.2 9.2 16 97.2 9.2 16
Length of stay (days)
Affas 201141 5.4 1.2 19 5.7 1.3 21 −0.3 [−0.5, −0.1] 0 0.005 Low
Carli 201013 5.7 2.6 20 5.2 2.4 20
Chaumeron 201314 6.6 2.1 29 6.8 2.6 30
Fan 201637 17.3 3.7 79 18.6 4.7 78
Kovalak 201542 4.6 0.7 28 4.8 0.7 32
Kutzner 201544 8.6 2.2 60 9.0 2.2 60
Moghtadaei 201438 5.0 1.5 18 5.0 1.1 18
Spangehl 201446 2.4 0.7 81 2.8 1.3 74

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 Local infiltration vs nerve block after knee replacement | 607

Table 4 Complications. CI, confidence interval; n, number of events; N total number of participants

Outcome Reference Group Relative risk I 2 (%) P value Quality of

Local infiltration Femoral [95% CI] evidence
analgesia nerve block (GRADE)

n N n N
14
Neurologic events Chaumeron 2013 1 29 1 30 0.7 [0.1, 4.0] 0 0.67 Very low
Moghtadaei 201438 1 18 2 18
Uesugi 201440 0 100 0 100
Cardiovascular events Affas 201141 0 20 0 20 3.8 [0.4, 33.0] 0 0.23 Very low
Carli 201013 1 20 0 20
Toftdahl 200747 2 40 0 37
Falls Chaumeron 201314 0 29 1 30 0.2 [0.0, 1.8] 0 0.16 Low
Spangehl 201446 0 81 3 79
Knee infections Carli 201013 0 20 0 20 1.6 [0.2, 12.6] 29 0.66 Moderate
Chaumeron 201314 0 29 2 30
Kovalak 201542 0 28 0 32
Moghtadaei 201438 1 18 0 18
Ng 201245 0 16 0 16
Parvataneni 200739 0 31 0 29
Toftdahl 200747 3 40 0 47
Uesugi 201440 0 100 0 100

attention to quality indicators around functional recovery and
complication rates.49 50 The choice of anaesthetic and analgesic
technique may be therefore be critical. However, our results sug-
gest that there is presently no evidence to argue for improved re-
covery with either LIA or FNB.
Apart from the goal of analgesic optimization, peripheral
nerve blockade has been questioned because of the potential
for motor blockade and suggested potential for falls during the
recovery period. Ilfeld and colleagues 51 reported a significant
difference in fall rates between placebo infusion vs local
anaesthetic (0% vs 7%, P=0.013) during continuous FNB. This
risk remains controversial with other trials suggesting no asso-
ciation,2 including a large administrative database review of
191,570 TKA patients.52 Although LIA avoids blockade of the
motor fibres to the quadriceps muscles, this meta-analysis
found no difference in the reported rate of motor related compli-
cations, including falls, when compared with FNB. A potential
confounder of this comparison was the inclusion of adductor
canal studies in the meta-analysis search criteria. However, no
trial using this technique met the inclusion criteria for this
meta-analysis.
Of note, one concern raised with LIA is the large dose of
local anaesthetic used during infiltration. Affas and collea-
gues53 performed quantitative analysis of plasma ropivacaine
concentrations after both LIA and repeated FNB. They identi-
fied no difference in maximum plasma concentrations, when
similar total doses of ropivacaine were administered, however
the median plasma concentration was significantly higher in
the LIA group. These authors did not report any signs of clinical
local anaesthetic toxicity, a finding consistent with our results.
Additional concerns regarding the LIA technique include the
wide range of injectate volume between 42 and 350 ml, dif-
ferences of adjuncts injected, unestablished stability of the
mixture and off-label route of administration for certain
drugs (e.g., non-steroidal anti-inflammatory drugs). In the ab-
sence of a clear rationale behind the mixture administered,
animal data and consensus among orthopaedic societies,
there is a compelling need for improved standardization of
the LIA procedure.
Our meta-analysis has several limitations. Although we at-
tempted to explain the observed heterogeneity by grouping re-
sults according to the specialization of the corresponding
author, heterogeneity remained moderate. This finding may
potentially be explained by the large variations in volumes and
adjuncts injected for LIA. Except for pain outcomes on post-
operative day one, fewer than half of the included trials reported
the same acute-pain related outcomes. In addition, functional
outcomes were frequently not reported. Consequently, the im-
pact of each intervention on functional outcomes during post-
operative recovery remains undetermined. Additional research
comparing both techniques with an eye to intermediate and
long-term functional recovery, would be a highly valuable add-
ition to the current literature.
In conclusion, LIA provides similar postoperative analgesic ef-
ficacy to FNB after total knee arthroplasty, but requires a higher
dose of local anaesthetic. The reported incidence of complica-
tions does not differ between groups although systemic concen-
trations of local anaesthetic cannot be determined from the
included trials. The degree of results heterogeneity suggests
that these findings should be interpreted with caution. Similarly,
the number of included trials for many outcomes remains small
and there is a need for more comprehensive standardized com-
parative evaluations of functional outcomes after these two
techniques.
Authors’ contributions
Study design/planning: E.A.
Study conduct: E.A., A.J.G., K.R.K.
Data analysis: E.A., A.J.G.
Writing paper: E.A., K.R.K.
Revising paper: all authors
Acknowledgments
We are grateful to Mrs Isabelle von Kaenel for the assistance
in the literature search. Head librarian, Lausanne University
Hospital, Lausanne, Switzerland.

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 608 | Albrecht et al.
Declaration of interest
E.A. has received grants from the Swiss Academy for Anaesthesia
Research (SACAR), Lausanne, Switzerland (no grant numbers at-
tributed) and from B.Braun Medical AG, Sempach, Switzerland
(no grant numbers attributed).
Funding
This work was supported by departmental funding (Depart-
ment of Anaesthesia, Lausanne University Hospital, Lausanne,
Switzerland).
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Handling editor: J. G. Hardman