British Journal of Anaesthesia 113 (3): 360–74 (2014)

Advance Access publication 17 June 2014 . doi:10.1093/bja/aeu155

Analgesic efficacy of local infiltration analgesia in hip and knee

arthroplasty: a systematic review
L. Ø. Andersen 1,2* and H. Kehlet 1,3

1
The Lundbeck Centre for Fast-track Hip and Knee Arthroplasty, Copenhagen, Denmark
2
Department of Anesthesiology and Intensive Care, Bispebjerg Hospital, Copenhagen, Denmark
3
Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
* Corresponding author. E-mail: lasseandersen@email.dk

Editor’s key points
† Growing interest in local
infiltration pain relief has
led to novel management
of patients in hip and knee
arthroplasty.
† The authors examined the
evidence base for this
practice, finding better
support for its use in knee
surgery than in hip
surgery.
† Wound infusion catheters
were not shown to provide
additional benefit, and
length of hospital stay
appeared unaffected by
local infiltration protocols.
In recent years, there has been an increasing interest in local infiltration analgesia (LIA) as a
technique to control postoperative pain. We conducted a systematic review of randomized
clinical trials investigating LIA for total knee arthroplasty (TKA) and total hip arthroplasty
(THA) to evaluate the analgesic efficacy of LIA for early postoperative pain treatment. In
addition, the analgesic efficacy of wound catheters and implications for length of hospital
stay (LOS) were evaluated. Twenty-seven randomized controlled trials in 756 patients
operated on with THA and 888 patients operated on with TKA were selected for inclusion in
the review. In THA, no additional analgesic effect of LIA compared with placebo was
reported in trials with low risk of bias when a multimodal analgesic regimen was
administered perioperatively. Compared with intrathecal morphine and epidural analgesia,
LIA was reported to have similar or improved analgesic efficacy. In TKA, most trials reported
reduced pain and reduced opioid requirements with LIA compared with a control group
treated with placebo/no injection. Compared with femoral nerve block, epidural or
intrathecal morphine LIA provided similar or improved analgesia in the early postoperative
period but most trials had a high risk of bias due to different systemic analgesia between
groups. Overall, the use of wound catheters for postoperative administration of local
anaesthetic was not supported in the included trials, and LOS was not related to analgesic
efficacy. Despite the many studies of LIA, final interpretation is hindered by methodological
insufficiencies in most studies, especially because of differences in use of systemic analgesia
between groups. However, LIA provides effective analgesia in the initial postoperative period
after TKA in most randomized clinical trials even when combined with multimodal systemic
analgesia. In contrast, LIA may have limited additional analgesic efficacy in THA when
combined with a multimodal analgesic regimen. Postoperative administration of local
anaesthetic in wound catheters did not provide additional analgesia when systemic analgesia
was similar and LOS was not related to use of LIA with a fast-track set-up.
Keywords: anaesthesia, local; arthroplasty; pain, postoperative

Local infiltration analgesia (LIA) with intra-operative adminis-
tration of local anaesthetic in various combinations with epi-
nephrine, non-steroidal anti-inflammatory drugs, opioids,
steroids, or all to the wound is a simple, surgeon-administered
technique for the treatment of postoperative pain after hip
(THA) and knee (TKA) arthroplasty.1 – 7 The technique may be
supplemented by placement of a wound catheter intended
to prolong analgesia by infusion of local anaesthetic (and
other analgesics) to the wound in the postoperative period.5 8 9
The LIA technique was originally presented by Bianconi and
colleagues,10 Kerr and Kohan11, and others, with promising
preliminary results especially from a non-randomized observa-
tional study in 325 patients demonstrating excellent pain
control and discharge from hospital the day after surgery in
71% of patients.11 The technique has gained widespread
use12 – 14 although the optimal design of the LIA technique
(i.e. infiltration technique, drug mixture, use of wound cathe-
ters, etc.) has not been completely evaluated.5
However, the specific evidence of analgesic efficacy of
LIA after THA and TKA has been confounded by frequent
limitations in study design because of the lack of comparable
systemic analgesia between groups. Furthermore, wide varia-
tions in the LIA technique/drug combinations have been
used in the clinical trials.
We, therefore, critically evaluated the analgesic efficacy of
intra-operative LIA in THA and TKA in a systematic search
and review of the available randomized clinical trials in the
early (,72 h) postoperative period along with an assessment

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LIA in hip and knee arthroplasty
of the risk of bias in each individual trial. Secondary outcomes
were assessment of the analgesic efficacy of wound catheters
determined by postoperative opioid consumption and implica-
tions for length of hospital stay (LOS).
Methods
Search strategy and criteria
Protocol and registration: the review protocol was not regis-
tered prior to data collection and writing of the manuscript.
Types of studies: prospective randomized clinical trials inves-
tigating analgesic efficacy of intra-operative peri-articular
injection of local anaesthetic for THA and TKA.
Types of participants: participants of any age operated on
with TKA or THA.
Types of intervention: trials comparing the analgesic efficacy
of intra-operative local anaesthetic infiltration with placebo
(saline or no injection), peripheral nerve block techniques
(PNB), continuous epidural analgesia, or intrathecal mor-
phine. In addition, clinical trials evaluating the analgesic
effect of postoperative local anaesthesia administration
through wound/intra-articular catheters.
Types of outcome measures: primary outcome measure was
postoperative pain recorded on a visual analogue scale or
numeric rating scale. Secondary outcome measure was
postoperative opioid consumption and LOS.
Information sources: literature search was performed using
the National Institute of Health PubMed database, Google
Scholar, and the Cochrane Library without language, age,
or gender restrictions.
Search: search was performed using the terms ‘local infiltra-
tion analgesia’, ‘LIA’, ‘hip arthroplasty’, ‘THA’, ‘knee arthro-
plasty’, and/or ‘TKA’. The reference list of each identified
trial was reviewed to ensure inclusion of all randomized con-
trolled trials investigating LIA for THA or TKA. Trials published
until June 1, 2013 were included. Selected recent publica-
tions thereafter were only included in the discussion.
Study selection: the authors independently performed as-
sessment of study eligibility in an unblinded manner and dis-
agreement was resolved by consensus.
Data collection process: data were independently extracted
by the authors from each included trial.
Data items: information on (a) study characteristics, partici-
pants, and design, (b) type of intervention (including specific
LIA technique applied), (c) type of systemic analgesia, (d)
pain and opioid requirements in the early (,72 h) period,
and (e) analgesic efficacy of supplemental wound catheter
administration of local anaesthetic in the postoperative
period along with (f) LOS was extracted from each included
trial and summarized
Risk of bias in individual studies: a summary assessment of
risk of bias in individual studies was performed in accord-
ance with the preferred reporting items for systematic
reviews and meta-analyses (PRISMA) statement.
Summary measures: study outcomes were summarized
with qualitative interpretation of individual studies
methods and results.
BJA
Results
A total of 27 studies were identified for inclusion in the review.
The search of PubMed, Google Scholar, and the Cochrane library
with combined search terms produced 43 citations of which 14
were excluded because they did not meet the inclusion criteria
as described on the basis of title and abstract. An additional
two studies8 9 were excluded from the review after detailed as-
sessment because these trials did not meet the inclusion cri-
teria as described. No additional studies were identified after
checking the reference lists of identified trials and unpublished
studies were not searched for (Fig. 1).
All 27 studies selected for the review were randomized con-
trolled trials and involved 888 patients operated on with TKA
and 756 patients operated on with THA. The study character-
istics are outlined in Table 1 (THA) and Table 2 (TKA).
Primary study outcome measures included pain at rest
and with mobilization measured on a visual analogue scale,
cumulated opioid consumption in the postoperative period
and time to discharge readiness, actual LOS, or functional
outcome measures such as range of knee motion. A summary
of study outcome measures is presented in Table 1 (THA) and
Table 2 (TKA).
Risk of study bias of included trials is summarized in Table 3
(THA) and Table 4 (TKA). In THA only 2 trials (including 132
patients) were considered with a low risk of bias (Table 3).
The remaining 8 trials investigating the analgesic efficacy of
LIA for THA were all confounded by incomplete blinding or
because systemic analgesia (NSAID) was different in control
and intervention groups thereby preventing interpretation
of LIA per se. In TKA only 2 trials (including 28 patients/56
knees operated on with simultaneous bilateral knee arthro-
plasty) could be considered with low risk of bias (Table 4).
The remaining 15 trials in TKA were inadequately blinded or
did not include similar systemic analgesia in intervention and
control groups and therefore prevented interpretation of the
LIA per se.
Studies comparing LIA with saline injections
or no injections
In this subgroup, 7 randomized trials in THA15 – 21 including 496
patients compared LIA with saline or no injections (Table 1).
Only two of these trials had low risk of bias (Table 3) with iden-
tical systemic analgesia in both groups,17 18 and in these trials
postoperative pain sores were very low and no statistically
significant differences in pain scores or opioid requirements
were observed in the early postoperative period (0–24 h post-
operatively) when LIA was combined with a multimodal
systemic analgesic regimen with acetaminophen, celecoxib,
and gabapentin (Table 1).
In TKA 7 randomized trials25 – 31 including 328 patients
investigated the analgesic efficacy of LIA compared with
saline or no injection (Table 2). Six of these trials25 – 28 30 31
reported reduced pain scores and reduced opioid consumption
in the early postoperative period (0–32 h postoperatively) and
1 trial comparing LIA with placebo in combination with a
femoral nerve block (FNB) in both groups reported similar
361
BJA Andersen and Kehlet

Literature search

• Databases: PubMed, Google Scholar and the Cochrane

Library

• Limits: prospective randomized clinical trials investigating

analgesic efficacy of intra-operative peri-articular
injection of local anaesthetic for hip, or both knee,
arthroplasty without age or language restrictions

Search results combined (n=43)

Articles screened on basis of title and abstract

Excluded (n=14)

LIA in combination with other postoperative analgesic regimen (n=1)

Not THA or TKA (n=7)

Included (n=29)
Not investigating analgesic effect of LIA (n=6)

Manuscript review and application of inclusion criteria

Excluded (n=2)

Not investigating intra-operative infiltration (n=2), but included in

discussion on wound catheter and site of administration

Included (n=27)

LIA vs placebo (n=14) LIA vs PNB (n=5) LIA vs epidural (n=4) LIA vs systemic LIA vs intra-
analgesia(n=1) thecal morphine
(n=3)

Fig 1 Flow diagram of study selection.

analgesic efficacy in the initial 24 h after surgery.29 However,
only two of these trials had low risk of bias27 28 and the remain-
ing studies were confounded by incomplete blinding or un-
matched systemic analgesia between groups (Table 4).
Studies comparing LIA with PNB
In THA no studies compared LIA with PNB.
In TKA 5 studies including 307 patients compared LIA with
single-shot or continuous femoral nerve block (cFNB).23 32 – 35
One trial compared cFNB in combination with LIA with cFNB
in combination with a reduced LIA including only infiltration
of the posterior part of the knee joint capsule, and therefore,
the reported similar analgesic efficacy in both groups does
not fully allow concluding whether one technique (LIA) is su-
perior to the other (cFNB).33 The remaining four trials were con-
founded by incomplete blinding and systemic analgesia was
not similar in the two groups. In one trial LIA provided superior
analgesia with reduced pain scores only the day after surgery
and reduced need for opioid in the initial 32 h after surgery

362
 LIA in hip and knee arthroplasty
Table 1 Randomized trials investigating LIA for THA

Author, year Procedure Study design Intraoperative Catheter Postop. injection(s) Outcomes (time after Comment
(number of injection total volume) placement time/volume/type surgery) LIA vs control
patients)
LIA vs placebo/no injection
Andersen, 200715 THA (37) Intraoperative Ropivacaine (300 mg) Intra-articular 24 h/21.5 ml  pain (4 h, 8 h, POD † Double-blinded design
periarticular injection vs Ketorolac (30 mg) Ropivacaine 300 mg 1 –4, 1+2 weeks) † No ketorolac in the control group
placebo Epinephrine (0.5 mg) Ketorolac 30 mg opioid (8– 96 h) † Systemic analgesia with paracetamol
(151.5 ml) Epinephrine 0.5 mg  physical function 1 g/6 h and oxycodone p.n.
(1 week)
Busch, 201016 THA (64) Intraoperative Ropivacaine (400 mg) – –  opioid (6, 24 h) † No morphine or NSAID in the control
periarticular injection vs Ketorolac (30 mg)  pain on activity (PACU) group
no injection Morphine (5 mg) ↔ pain at rest † Multiple anaesthetic procedures
Epinephrine (0.6 mg) ↔ patient satisfaction (general/regional)
↔ postoperative † Pain assessment time poorly defined
complications † Pain on activity poorly defined
- ropivacaine dose below † Systemic analgesia with morphine-PCA
toxic level (n¼5) and oral paracetamol, caffeine, codeine
↔ LOS and oxycodone
Andersen, 201017 Bilateral THA Intraoperative Ropivacaine (340 mg) Intra-articular 8+24 h/20+50 ml ↔ pain (0 – 48 h) † Double-blinded design
(12) periarticular injection vs Epinephrine (1.2 mg) Ropivacaine † Systemic analgesia with gabapentin,
placebo 40+100 mg celecoxib and paracetamol resulted in
Epinephrine low postoperative pain scores
(1:100 000)
Lunn, 201118 THA (120) Intraoperative Ropivacaine (300 mg) – – ↔ pain (0 – 8 h) † Double-blinded design
periarticular injection vs Epinephrine (1.5 mg) ↔ opioid (0 –8 h) † Systemic analgesia with gabapentin,
placebo (150 ml) celecoxib and paracetamol resulted in
low postoperative pain scores
Murphy, 201119 THA (91) Intraoperative Levobupivacaine – – ↔ pain (0 – 72 h) † No description of how pain data were
periarticular injection vs (150 mg)  opioid (0 –48 h) collected
placebo (60 ml) ↔ PONV † Surgeon not blinded to injection type
† Systemic analgesia with morphine-PCA
0 –48 h
Dobie, 201220 THA (92) Intraoperative Levobupivacaine – –  pain (7+12 h) † No clear description of how pain data
periarticular injection vs (200 mg) ↔ opioid (0 –24 h) were collected
no injection Epinephrine ↔ mobilization (24 h) † Systemic analgesia with i.v. morphine
(1:200 000) ↔ LOS (10 mg/4 –6 h) and paracetamol 1 g/6 h.
(160 ml) † Low postoperative pain scores in both
groups
Liu, 201221 THA (80) Intraoperative Bupivacaine (30 mg) – –  opioid (0 –36 h) † Double-blinded design
periarticular injection vs Morphine (5 mg)  pain (6 –36 h) † No morphine or betamethasone in the
placebo Betamethasone (1 ml)  ROM (24 h, POD 2+7) control group
Epinephrine (1:1000) † Systemic analgesia with morphine-PCA
(60 ml) and celecoxib 200 mg/12 h
LIA vs epidural analgesia:
Andersen, 200722 THA (75) Intraoperative Ropivacaine (200 mg) Intra-articular 8 h/20 ml  pain (20 – 96 h) † Non-blinded design
periarticular injection vs Ketorolac (30 mg) Ropivacaine 150 mg  opioid (0 –20 h) † No control for morphine (epidural group)
epidural Epinephrine (0.5 mg) Ketorolac 30 mg  ability to walk (8 h) or ketorolac (LIA group) in either group
(102 ml) Epinephrine 0.5 mg  LOS (4.5 vs 7 days) † Systemic analgesia with paracetamol
 side-effects 1 g/6 h and oxycodone p.n.

BJA
363

Continued
BJA Andersen and Kehlet

compared with cFNB.32 In the trial by Parvataneni and collea-

gues23, systemic analgesia was different between groups hin-

† No ketorolac in the intra-thecal morphine

† Groups not comparable with injection of

group and undefined opioid-PCA in the

† Systemic analgesia with paracetamol

dering conclusions on analgesic efficacy of LIA per se. The trial

morphine and steroid only in the LIA

1 g/8 h and ibuprofen 400 mg/12 h

by Affas and colleagues34 was not blinded and reported equal

† Inadequate definition of systemic

† Patient and investigator blinded

analgesic efficacy of LIA compared with FNB in the first 24 h
after surgery. The randomized trial by Koh and colleagues35
compared LIA on top of cFNB with cFNB alone, and reported
† Not double-blinded

control group only.

reduced pain with LIA in the initial 48 h along with reduced
need for opioid in the initial 24 h after surgery. Interpretation
and conclusions of these trials is furthermore hindered by dif-
analgesia
Comment

ferent techniques of PNB (Table 2).

group
Studies comparing LIA with epidural analgesia
↔ mobilization (6 weeks
surgery) LIA vs control

In THA, 1 trial in 75 patients compared LIA with continuous

 LOS (3.2 vs 4.2 days)
Outcomes (time after

 satisfaction (POD 1)
pain (POD1,2 and 3)

epidural analgesia.22 The results demonstrated reduced pain

 opioid (0 –24 h)
↔ pain (0 – 48 h)

20–96 h postoperatively and reduced need for opioid 8–96 h

and 3 months)

 mobilization

postoperatively with LIA. This trial has high risk of bias

(6+24 h)
↔ PONV

because of the non-blinded design and because systemic

analgesia was different between groups (Table 1).
In TKA, 3 trials in 204 patients investigated the analgesic ef-
ficacy of LIA compared with continuous epidural analgesia.36 – 38
Postop. injection(s)
time/volume/type

The trial by Spreng and colleagues36 reported increased pain

Levobupivacaine

Ketorolac 30 mg

with LIA on the day of surgery but decreased pain and opioid
24 h/21 ml

requirements on postoperative days 1–3. Furthermore, LIA

100 mg

with local infiltration of NSAID provided improved analgesia by

–

5–10 mm on the VAS scale compared with similar systemic ad-

ministration of NSAID. Of the remaining two trials, the trial by
Intra-articular

Thorsell and colleagues38 reported reduced pain scores and

placement
Catheter

similar opioid consumption up to 72 h after surgery with LIA

compared with epidural, but this trial has a high risk of bias
–

because of incomplete descriptions on how pain was recorded

injection total volume)

Bupivacaine 2 –400 mg

and because the trial was not blinded. In the trial by Andersen
Epinephrine (0.5 mg)
Prednisolone 40 mg

and colleagues37 LIA was reported to reduce pain scores 2–72

Cefuroxime 750 mg
Epinephrine 0.3 mg
Morphine 4 –10 mg

Ketorolac (30 mg)

Levobupivacaine

h postoperatively along with a reduction in opioid requirements

Intraoperative

in the initial 48 h, but again with different systemic analgesia

(125 mg)

(106 ml)

between groups hindering interpretation of LIA per se. All

trials had high risk of bias because of incomplete blinding
(?)

along with different systemic analgesia between groups.

periarticular injection vs
intra-thecal morphine
Intraoperative local

Studies comparing LIA with systemic analgesia

infiltration vs PCA

In the only study, Parvataneni and colleagues23 randomized 71

Intraoperative
Study design

patients operated on with THA to LIA with bupivacaine, mor-

phine, epinephrine, prednisolone, and antibiotics vs patient-
controlled analgesia with opioid (undefined). In this trial,
patients treated with LIA reported reduced pain on post-
operative days 1–3 along with a reduction in LOS (3.2 vs 4.2
(number of
Procedure

days). However, this trial also has a very high risk of bias
patients)

THA (71)

THA (60)

because of inadequate definitions of the systemic analgesia

LIA vs intra-thecal morphine

administered and because the trial was not blinded. Further-

LIA vs systemic analgesia:

more, the administration of multiple analgesic drugs simultan-

Rikalainen-Salmi,
Table 1 Continued

eously and in unspecified amount hinders exact interpretation

Parvataneni,

of the results.
Author, year

200723

201224

Studies comparing LIA with intra-thecal morphine

In THA, 1 trial including 60 patients had compared LIAwith intra-
thecal morphine administration.24 This trial reported equal pain

364
LIA in hip and knee arthroplasty BJA

Table 2 Randomized clinical trials investigating the analgesic efficacy of LIA for TKA

Author, year Procedure Study design Intraoperative Catheter Postoperative Outcomes, LIA Comment
(number of injection, type, placement injection(s) vs control
patients) (total volume) time/volume/ (time after
type surgery)
LIA vs placebo/no injection
Busch, 200625 TKA (64) Intraoperative Ropivacaine – –  pain (4 h) † Not
local infiltration vs 400 mg  opioid (6, 12, observer-blinded
no injection Ketorolac 24 h) † No ketorolac and
30 mg  satisfaction morphine in the
Epimorphine (4 h) control group
5 mg ↔ ROM † Anaesthesia not
Epinephrine (6 weeks) standardized
1:100 000 Plasma (general and
(100 ml) ropivacaine regional)
concentration † Systemic
below toxic analgesia with
levels (n¼5) morphine-PCA in
both groups
Vendittoli, TKA (42) Intraoperative Ropivacaine Intra-articular 20 h/15 ml/  pain † Double-blinded
200626 local infiltration vs 275 mg Ropivacaine (24, 48 h) design
no injection Epinephrine 150 mg  opioid (8, 16, † No control for
1:100 000 24, 48 h) ketorolac in the
Ketorolac ↔ ROM (5 control group
30 mg days) † Spinal anaesthesia
(160 ml) (all patients)
† Systemic
analgesia with
paracetamol 500
mg/6 h+celecoxib
200 mg/12 h,
morphine-PCA in
both groups
Andersen, Bilateral Intraoperative Ropivacaine Intra-articular 8 and 24 h/  pain (4 –32 h) † Double-blinded
200827 TKA (12) local infiltration vs 340 mg 20+50 ml/ design in bilateral
placebo Epinephrine Ropivacaine knee arthroplasty
1.2 mg 40/100 mg † Systemic
(170 ml) Epinephrine analgesia with
(1:100 000) paracetamol (slow
release) 2 g/12 h,
celecoxib 200 mg/
12 h and
gabapentin
(300+600 mg)
Andersen, Bilateral Intra- and Ropivacaine Subcutaneous 6 and 24 h/20 ml  Pain 1 –6 h † Double-blinded
201028 TKA (16) postoperative 500 mg Ropivacaine ↔ pain (24 h design in bilateral
subcutaneous Epinephrine 100 mg postoperative knee arthroplasty
injection vs 2 mg injection) † Systemic
placebo (250 ml) analgesia with
paracetamol (slow
release) 2 g/12 h,
celecoxib 200 mg/
12 h and
gabapentin
(300+600 mg)
Krenzel, TKA (66) Intraoperative Ropivacaine 2 2 ↔ pain † Double-blinded
200929 local 100 mg (4 –24 h) design
infiltration+FNB (20 ml) ↔ opioid † Systemic
vs placebo+FNB (4 –24 h) analgesia with
↔ celecoxib,
mobilization pregabalin and
(0 –24 h) fentanyl-PCA in
both groups
† Incomplete
description of

Continued

365
BJA Andersen and Kehlet

Table 2 Continued

Author, year Procedure Study design Intraoperative Catheter Postoperative Outcomes, LIA Comment
(number of injection, type, placement injection(s) vs control
patients) (total volume) time/volume/ (time after
type surgery)
methodology
(inclusion/data
recording)
Essving, TKA (48) Intra- and Ropivacaine Intra-articular .21 h/22 ml opioid (0– † Double-blinded
201030 postoperative 400 mg Ropivacaine 48 h) design
local infiltration vs Ketorolac 200 mg Pain 3 –48 h † No ketorolac in
no injection/saline 30 mg Ketorolac 30 mg  ROM control group
(postop. injection) Epinephrine Epinephrine (24+48 h) † Systemic
0.5 mg 0.1 mg Plasma analgesia with
(166 ml) ropivacaine paracetamol 1 g/
concentration 6 h and
below toxic morphine-PCA in
levels (n¼8) both groups
↔ long-term
outcomes
(3 months)
Zhang, 201131 TKA (80) 3 study groups: Ropivacaine Intra-articular 0–48 h/ 4 ml h21  opioid (24 – † Double-blinded
(a) LIA+postop. 300 mg Ropivacaine 48 h) with design
ropivacaine Ketorolac 2 mg ml21 or postop. † No ketorolac in
infusion 30 mg saline 0.9% ropivacaine inf. control group
(b) LIA+postop. Epinephrine  pain (8 –48 h) † Systemic
saline infusion 0.5 mg with postop. analgesia with
(c) postop. saline (152 ml) ropivacaine inf. morphine-PCA in
infusion  LOS (3 vs all groups
4 days) † Pain data recorded
 ROM by multiple
(7+90 days) (undefined)
 patient investigators
satisfaction
LIA vs PNB
Toftdahl, TKA (80) Intraoperative Ropivacaine Intra-articular 8 h and 24 h/ ↔ pain † Not
200732 local infiltration vs 300 mg 20+20 ml/ (0 –24 h) observer-blinded
FNB Ketorolac Ropivacaine pain (POD1) † Intraarticular
30 mg 200 mg ↔ pain (POD2) bupivacaine
Epinephrine Ketorolac 30 mg  opioid (50 mg) and
0.5 mg Epinephrine (0 –32 h) morphine (4 mg)
(150 ml) 0.5 mg  mobilization/ with PNB
ROM (POD 1,2) † Multiple
investigators
† Systemic
analgesia with
paracetamol
1 g/6 h, ibuprofen
400 mg/8 h and
oxycodone
20 mg/12 h
Parvataneni, TKA (60) Intraoperative Bupivacaine – – ↔ pain (POD 1, † Not
200723 local infiltration vs 2– 400 mg 2, 3, 14) double-blinded
FNB +PCA Morphine ↔ satisfaction † Groups not
4– 10 mg (6 weeks and comparable with
Epinephrine 3 months) injection of
0.3 mg ↔ ROM (POD 2 morphine and
Prednisolone and 3 months) steroid only in LIA
40 mg ↔ group and
Cefuroxime mobilization (6 undefined
750 mg weeks and opiod-PCA in
(total volume 3 months) control group only
not reported) † Inadequate
definition of
systemic
analgesia

Continued

366
LIA in hip and knee arthroplasty BJA

Table 2 Continued

Author, year Procedure Study design Intraoperative Catheter Postoperative Outcomes, LIA Comment
(number of injection, type, placement injection(s) vs control
patients) (total volume) time/volume/ (time after
type surgery)
Carli, 201033 TKA (40) Intraoperative Ropivacaine Intra-articular 24 h/50 ml ↔ pain (POD † Double-blinded
local infiltration 300 mg Ropivacaine 1+2) design
and postoperative Ketorolac 250 mg opioid † Intraoperative
intra-articular 45 mg Ketorolac 30 mg (0 –48 h) infiltration of
infusion vs Epinephrine Epinephrine  mobilization ropivacaine 100
continuous FNB 0.75 mg 0.25 mg POD 1+2 mg/ketorolac 30
(200 ml)  late recovery mg/epinephrine
of walking 0.25 mg also in the
capacity cPNB group
(6 weeks) † Systemic
analgesia with
celecoxib
100 mg/12 h,
acetaminophen
1 g/6 h and
morphine-PCA in
both groups
Affas, 201134 TKA (40) Intraoperative Ropivacaine – – ↔ opioid † Not blinded
local infiltration vs 300 mg (0 –24 h) † Systemic
FNB Ketorolac ↔ pain analgesia with
30 mg (0 –24 h) acetaminophen
Epinephrine 1 g/6 h and
0.5 mg morphine-PCA in
(156 ml) both groups
† Ketorolac
administered in
similar dose in
both groups
† Patients with
rheumatoid
arthritis not
excluded and not
similar between
groups
Koh, 201135 TKA (87) Intraoperative Ropivacaine – –  pain (0 –48 h) † Not
local 300 mg  opioid observer-blinded
infiltration+cFNB Morphine (0 –24 h) † Surgery performed
vs cFNB 10 mg ↔ ROM (7 days by a single surgeon
Ketorolac postoperative) and pain data
30 mg ↔ LOS recorded by a
Epinephrine single investigator
0.3 mg † No intraop.
Cefuroxime morphine/
750 mg ketorolac in
(100 ml) control group
† Systemic
analgesia similar
between groups
(ketorolac and
fentanyl-PCA)
LIA vs epidural analgesia
Spreng, TKA (99) 3 study groups: Ropivacaine Intra-articular 24 h/20 ml  pain (day † Double-blinded
201036 (a) epidural 150 mg Ropivacaine of surgery) design, but with
analgesia (48 h) Epinephrine 142 mg  pain incomplete
(b) LIA with local 0.5 mg Ketorolac 30 mg (POD 1 –3) blinding of the
NSAID and opioid +/2 Ketorolac (i.v. or i.a.) opioid (48 h, epidural group
(c) LIA with i.v. 30 mg 72 h) † Epidural analgesia
NSAID and opioid +/2 Morphine  mobilization not as effective as
5 mg (150 ml)  pain (POD otherwise
1– 3) with local reported
vs i.v. NSAID/ † Morphine (5 mg)

Continued

367
BJA Andersen and Kehlet

Table 2 Continued

Author, year Procedure Study design Intraoperative Catheter Postoperative Outcomes, LIA Comment
(number of injection, type, placement injection(s) vs control
patients) (total volume) time/volume/ (time after
type surgery)
opioid, mean administered in
difference 5 – LIA groups but not
10 mm (VAS 0 – the epidural group
100 mm) † Systemic
analgesia with
paracetamol 1 g/
6 h and
morphine-PCA
Andersen, TKA (40) Intraoperative Ropivacaine Intra-articular 0–48 h/192 ml  pain (2 –72 h) † Not
201037 local infiltration 300 mg Ropivacaine opioid observer-blinded
and postoperative Ketorolac 380 mg (0 –48 h) † No ketorolac in the
intra-articular 30 mg Ketorolac 60 mg control group
infusion vs Epinephrine 0.5 † Epidural analgesia
epidural analgesia mg (152 ml) not as effective as
otherwise
reported
† Systemic
analgesia with
paracetamol 1 g/
6 h and
morphine-PCA in
both groups
Thorsell, TKA (65) Intra- and Ropivacaine Intra-articular 24 h/20 ml  mobilization † Not
201038 postoperative 300 mg Bupivacaine  pain (2 –72 h) observer-blinded
local infiltration vs Ketorolac 100 mg ↔ opioid † No ketorolac in the
epidural analgesia 30 mg Ketorolac 30 mg (0 –48 h) control group
Epinephrine Epinephrine  patient † Incomplete
0.5 mg 0.1 mg satisfaction information on
(156 ml) pain data and
method of
recording
† Systemic
analgesia with
opioid alone
LIA vs intra-thecal morphine
Essving, TKA (49) Intraoperative Ropivacaine Intra-articular 21 and 45 h/22  opioid † Double-blinded
201139 local infiltration 400 mg ml Ropivacaine (0 –48 h) design
and postoperative Ketorolac 200 mg  pain (0 –48 h) † No ketorolac in the
intra-articular 30 mg Epinephrine  LOS control group
injections vs Epinephrine 0.1 mg (3 vs 4 days) (intrathecal
intrathecal 0.5 mg Ketorolac 30 mg ↔ ROM morphine)
morphine (166 ml)  mobilization † Systemic
(24+48 h) analgesia with
 patient morphine-PCA in
satisfaction both groups
Tammachote, TKA (57) Intraoperative Bupivacaine – – ↔ pain (0– 48 † Patient and
201340 local infiltration 100 mg h) observer blinded
and postoperative Morphine 5 mg ↔ ketorolac but surgeon not
intra-articular Ketorolac 30 (0 –48 h) blinded
injections vs mg  PONV (?) † Systemic
intrathecal Epinephrine ↔ LOS analgesia with
morphine (1:1000) ketorolac-PCA,
(100 ml) acetaminophen
and amitriptyline
† No intraoperative
systemic
morphine and
ketorolac in the
intrathecal
morphine group

368
LIA in hip and knee arthroplasty BJA

Table 3 Summary of the included studies investigating the analgesic efficacy of LIA for THA

Trials No. of Concealment of Patients Health care Data Outcome Systemic analgesia
patients randomization blinded providers collectors assessors similar between groups
blinded blinded blinded with control for
ketorolac in LIA
Andersen and 37 + + + + + 2
colleagues15
Andersen and 75 + 2 2 2 2 2
colleagues22
Parvataneni and 71 + 2 2 2 2 2
colleagues23
Busch and 64 + + + + + 2
colleagues16
Andersen and 12 + + + + + (no ketorolac in LIA)
colleagues17
Lunn and 120 + + + + + (no ketorolac in LIA)
colleagues18
Murphy and 91 + + 2 2 ? (no ketorolac in LIA)
colleagues19
Dobie and 92 + + ? ? ? (no ketorolac in LIA)
colleagues20
Rikalainen-Salmi and 60 + + + + + 2
colleagues24
Liu and colleagues16 80 + + + + + 2

scores in the initial 48 h after surgery in both groups, but with
increased need for opioid in the LIA group. Systemic analgesia
was not similar between groups imposing a high risk of bias.
In TKA, 2 trials comprising 106 patients investigated the
analgesic efficacy of LIA compared with intrathecal mor-
phine.39 40 Essving and colleagues39 reported reduced pain
scores and reduced opioid consumption in the first 48 h after
surgery with LIA compared with intrathecal morphine. System-
ic analgesia was not identical in the study groups imposing a
high risk of bias. Another trial including 57 patients demon-
strated similar analgesic efficacy with a multimodal peri-
articular injection with bupivacaine, ketorolac, morphine, and
epinephrine compared with 0.2 mg intrathecal morphine.40 No
control for local infiltration with morphine and ketorolac was
given to the control group imposing a risk of bias in this trial.
Analgesic efficacy of wound catheter administration
of local anaesthetic in the postoperative period
More than half of the trials included for this review (15/27 trials)
have included a woundcatheter for postoperative administration
of a local anaesthetic, in various combinations with ketorolac and
epinephrine.
In THA an intra-articular catheter was placed in four trials,
and postoperative administration of ropivacaine alone or in
combination with ketorolac was administered 8 or 24 h post-
operatively.15 17 22 24 None of these four trials has specifically
evaluated the potential analgesic efficacy of the wound cath-
eter administrations per se, and in two trials no difference in
postoperative analgesia was demonstrated.17 24 The remain-
ing two trials demonstrated improved analgesia with LIA+
wound catheter compared with the control groups (saline
and epidural analgesia, respectively), but the difference in an-
algesic efficacy was not demonstrated to be related to the
postoperative injections through the wound catheter.15 22
In TKA, an intra-articular wound catheter was included in
the LIA technique in 10 trials27 26 30 – 33 36 – 39 and in 1 trial a sub-
cutaneous catheter was placed.28
The analgesic efficacy of postoperative intra-articular ad-
ministration of local anaesthetic with ketorolac and epineph-
rine was not specifically evaluated in these 10 trials, but
overall nine of these trials26 27 30 31 – 36 37 – 39 reported
reduced pain and opioid requirements up to 72 h after
surgery compared with the control group. However, analgesia
may partly have derived from the intraoperative LIA alone, and
a specific analgesic efficacy of an intra-articular wound cath-
eter was not convincingly demonstrated in TKA. Thus, the inclu-
sion of ketorolac in the LIA solution may account for the
reported analgesic effect and not controlled for by similar sys-
temic administration of NSAID except for the positive trial of
Spreng and colleagues.36 A subcutaneous catheter with post-
operative administration of local anaesthetic 24 h postopera-
tively did not provide improved analgesia compared with
similar administration of saline in 16 patients operated on
with bilateral TKA in contrast to the analgesic effect by intra-
operative subcutaneous infiltration.28
Length of hospital stay
The randomized clinical trials with LIA for THA and TKA have
reported very variable data on LOS and potential reasons for
the differences in LOS were not described (Table 5). Thus, LOS
varied from 2.5 to 7 days in the included trials, and was not
related to the choice of analgesic technique in the trials

369
BJA Andersen and Kehlet

Table 4 Summary of the included studies investigating the analgesic efficacy of LIA for TKA

Trials No. of Concealment of Patients Health care Data Outcome Systemic analgesia
patients randomization blinded providers collectors assessors similar between groups
blinded blinded blinded with control for ketorolac
in LIA
Busch and 64 + + 22 2 2 2
colleagues25
Vendittoli and 42 + + + + + 2
colleagues26
Toftdahl and 80 + + 2 2 2 2
colleagues32
Paravataneni and 60 2 2 2 2 2 2
colleagues23
Andersen and 12 + + + + + (no ketorolac in LIA)
colleagues27
Krenzel and 66 ? + + ? ? (no ketorolac in LIA)
colleagues29
Andersen and 16 + + + + + (no ketorolac in LIA)
colleagues28
Essving and 48 + + + + + 2
colleagues30
Spreng and 99 + 2 2 2 + +
colleagues36
Andersen and 40 + 2 2 2 2 2
colleagues37
Thorsell and 65 2 2 2 2 2 ?
colleagues38
Carli and 40 + + + + + 2
colleagues33
Essving and 49 + + + + + 2
colleagues39
Affas and 40 + 2 2 2 2 +
colleagues34
Zhang and 80 + + + + + 2
colleagues31
Koh and 87 + 2 2 2 2 2
colleagues35
Tammachote and 57 + + 2 + + 2
colleagues40

(Table 5). Only 12 studies described well-defined discharge
criteria (Table 5), but LOS dependency of pain was not reported
in any study.
Discussion
Effective treatment of postoperative pain is important to allow
early rehabilitation along with early (,3 days) discharge from
hospital to home after THA and TKA.41 The LIA technique is of
clinical interest attributable to the simplicity and apparent
safety of the technique, although large-scale and sufficiently
powered safety studies of the technique are lacking.5 The LIA
technique has gained widespread use in recent years despite
relatively limited evidence of analgesic efficacy from rando-
mized and lack of properly designed clinical trials.1 2 4 5 6 7 14
TKA is associated with moderate-to-severe acute and sub-
acute postoperative pain27 42 and where different non-opioid
analgesic agents have been shown to provide some analgesia;
acetaminophen, NSAID and COX-2 inhibitors, gabapentin, and
glucocorticoid.43 44 In contrast, postoperative pain after THA is
less pronounced and therefore more effectively treated with
multimodal systemic analgesia.42 44 45 46 In spite of this,
most trials included in this review have made use of limited
or insufficient simple oral multimodal systemic analgesia
(Tables 1 and 2).
This systematic review summarizes the evidence for anal-
gesic efficacy of intraoperative wound infiltration of local an-
aesthetic in various combinations with NSAID, steroids,
opioids, and epinephrine (LIA). Overall, the randomized clinical
trials in TKA reported an analgesic efficacy of LIA in the early
postoperative period when compared with placebo or no
injection and most trials have reported decreased post-
operative pain and reduction in opioid requirements in the
early (,48 h) postoperative period.25 – 31 The analgesic efficacy

370
LIA in hip and knee arthroplasty BJA

Table 5 LOS in randomized trials using LIA for unilateral hip and knee arthroplasty. Data presented as days in hospital unless otherwise stated. TDR,
time to discharge readiness

Author, year LOS, LIA LOS, control Well-defined discharge criteria (+

+)
TKA
Busch, 200625 Mean 5.2 5.2 2
Vendittoli, 200626 Mean 4.8 5.2 +
Toftdahl, 200732 Median 5 6 2
Parvataneni, 200723 Not reported Not reported 2
Andersen, 200827 Mean 2.8 3.3 +
Andersen, 201028 Not reported Not reported +
Krenzel, 200929 Not reported Not reported 2
Essving, 201030 Median 3 5 +
Spreng, 201036 TDR mean 3.5 and 4.0 TDR 5.5 +
Andersen, 201037 Median 4 4 +
Carli, 201033 Median 5 5 2
Thorsell, 201038 Mean 4.7 5 2
Essving, 201139 Median 3 4 +
Affas, 201134 Not reported Not reported 2
Zhang, 201131 Not reported Not reported 2
Koh, 201135 Not reported Not reported 2
Tammachote 201340 Not reported Not reported 2
THA
Andersen, 200715 Mean 2.6 2.8 +
Andersen, 200722 Median 4.5 7 +
Parvataneni, 200723 Not reported Not reported 2
Andersen, 201117 Median 4 4 +
Busch, 201016 Mean 5.2 5.8 2
Lunn, 201118 Mean 2.7 2.5 +
Murphy, 201119 Not reported Not reported 2
Dobie, 201220 Mean 3.5 3.9 2
Liu, 201121 Not reported Not reported 2
Rikalainen-Salmi, 201224 Median 4 4 +

of LIA per se was also supported in a trial in bilateral knee
arthroplasty where patients served as their own controls.27
However, in most of these trials, and more recent studies,47
repeated injections in wound-placed catheters were done,
but without control for local vs systemic NSAID, limiting inter-
pretation on the duration intraoperative LIA. In THA, seven
trials have compared LIA with placebo or no injection,15 – 21
but only two of these trials, including the largest (n¼120)
trial, incorporated similar systemic analgesia in intervention
and control groups and concluded that LIA provided no add-
itional analgesic effect when combined with a multimodal an-
algesic regimen consisting of acetaminophen, celecoxib, and
gabapentin.17 18 The remaining trials were in risk of bias by
not using a blinded design or because systemic analgesia
was different between groups.
Trials comparing LIA with FNB in TKA mostly reported equal
analgesic efficacy of these techniques23 32 – 35 but with differ-
ent nerve block techniques. Furthermore, these trials did not
include similar systemic control for local infiltration of ketoro-
lac with LIA in the FNB group hindering final conclusions.
However, a FNB may hinder early postoperative mobilization
because of the motor block of the quadriceps muscle, and
patients may have a risk of falling in the first days after
surgery because of the block.48 For these reasons LIA may be
preferable to a FNB, although the latter remains the ‘golden
standard’ after TKA.46 Data on PNB compared with LIA in THA
were not retrieved from the search in this review.
Data comparing LIA with continuous epidural analgesia
are limited, although one trial in THA22 and three trials in
TKA36 – 38 have compared the analgesic efficacy of these
techniques. Although the results may favour LIA over con-
tinuous epidural analgesia, most trials were not sufficiently
blinded or applied different systemic analgesia in the study
groups without control for ketorolac in the LIA solution
(Tables 3 and 4). Furthermore, the epidural analgesia tech-
nique was different between trials and overall continuous
epidural analgesia is not recommended in THA or TKA
because of side-effects.49
LIA has not been sufficiently evaluated in randomized trials
investigating the analgesic efficacy compared with different
multimodal systemic analgesia. However, the two trials in
THA comparing LIA with saline injection with application of a

371
BJA
multimodal systemic analgesic regimen demonstrated very
low pain scores and equally low opioid requirements in this
setting, seriously questioning the analgesic potential of LIA
in THA.17 18
Compared with intra-thecal morphine, LIA may provide
similar (two trials) or improved (one trial) analgesia.24 39 40
However, intrathecal morphine may not be recommended as
first-choice for neither TKA nor THA45 46 and the available
data are in high risk of bias because of the lack of blinding or dif-
ferent systemic analgesia administered in intervention and
control groups along with a lack of control for ketorolac in the
LIA solution (Tables 3 and 4).
Most of the available studies were not designed to assess
the analgesic efficacy of postoperative local anaesthetic ad-
ministration in TKA or THA, and have made use of an
intra-articular catheter for postoperative injection as part of
the LIA technique but without evaluation of the analgesic effi-
cacy of postoperative injections. Also other studies with single
injection of intra-articular injection of local anaesthetic have
mostly been negative.50 Most importantly, interpretation is
limited by the lack of control for NSAID in the LIA solution,
and without similar NSAID administration in the control
group, except one study.36 Postoperative administration of
local anaesthetic through wound catheters may have no or
limited analgesic efficacy in THA and TKA, regardless of
anatomic placement (intra-articular, subcutaneous, or intra-
capsular placement).8 9 28 51 52 Furthermore, the volume/
concentration relationship of local anaesthetics delivered
through a wound catheter may be of minor clinical relevance.53
While LIA is administered intra-operatively to all tissues
incised or instrumented in most trials,54 only few trials have
investigated the optimal anatomical location of local anaes-
thetic administration (i.e. anterior or posterior joint capsule,
subcutaneous tissue, muscle, synovia along with comparisons
of the relative importance of infiltration of these different ana-
tomical locations). However, it has been concluded that the
subcutaneous infiltration is necessary to provide sufficient an-
algesia in the early postoperative period.28
The choice of analgesic technique may have very limited
impact on LOS beyond 24 h and organizational issues, with a
well-organized fast-track set-up, may be the most important
factor for achieving a short stay around 2– 3 days after TKA.55
The local infiltration of NSAID may have limited analgesic ef-
ficacy when compared with similar systemic administration56
but in the only one trial investigating locally vs systemically
administered NSAID with LIA, the reported analgesic potential
was limited (around 5–10 mm on a VAS scale).36
This review may be limited by possible incomplete retrieval
of relevant randomized clinical trials, although the search was
performed repeatedly and the authors have published clinical
trials and reviews on the subject in the past decade.
However, it cannot be excluded that some studies were not
identified from the search as presented. Another limitation to
the study may be that the studies identified and included in
this systematic review were only assessed by the two authors
and not by a larger group of independent investigators which
may have biased the assessment of individual trials.
372
Andersen and Kehlet
However, the assessments were performed in a systematic
and similar manner for all trials included, in accordance with
the PRISMA statement and the Cochrane Handbook for Sys-
tematic Reviews guidelines for assessing individual studies’
risk of bias. A further limitation to this review may be the lack
of a direct comparison and meta-analysis of study outcome
measures (pain, opioid requirements). However, the included
trials varied widely in design of the LIA technique rendering a
systematic comparison of outcome measures unlikely to
produce relevant new data on the analgesic efficacy of LIA in
THA and TKA.
In conclusion, intra-operative LIA may have an analgesic
effect in the early postoperative period after TKA as demon-
strated in 4 trials with low risk of bias, but not in THA when
multimodal systemic analgesia is provided. LIA may be
equally effective (four trials) or provide superior analgesia
(one trial) compared with FNB in TKA, but all trials have a
high risk of bias because of insufficient study design and
because different nerve block techniques were applied
thereby hindering conclusions. Compared with continuous epi-
dural analgesia results are limited but demonstrates improved
or similar analgesia with LIA. However, continuous epidural an-
algesia is not recommended after TKA or THA because of the
relatively high risk of side effects. Compared with intrathecal
morphine, the data are limited and inconclusive because of in-
sufficient design.
Overall, most trials have not included a systemic control for
locally infiltrated ketorolac with LIA in the control group, and/or
have applied different systemic or insufficient systemic anal-
gesia in study groups making final conclusions difficult on the
analgesic efficacy of LIA per se.
Future randomized controlled trials investigating the
analgesic efficacy of LIA in major joint arthroplasty should
incorporate optimized oral multimodal systemic analgesic
regimens comprising perioperative treatment with paracetamol,
an NSAID/COX-2 inhibitor, and possibly a gabapentinoid along
with morphine for rescue analgesia. Importantly, future trials
should apply identical systemic analgesia in study groups, includ-
ing control for NSAID in the LIA solution, to allow more definite
conclusions on the analgesic efficacy of the technique. These
strategies would allow a more precise comparison of the data
collected from future trials and meta-analysis of the combined
data. Finally, the efficacy–side-effect relation of incorporating
NSAID in the LIA solution requires further studies and the use
of catheter techniques in TKA.
Authors’ contributions
Both authors performed the literature search independently
and contributed equally to analysis of the collected trials for in-
clusion in the review along with interpretation of study results.
L.Ø.A.: writing of the manuscript including tables and figure.
H.K.: detailed contributions to manuscript revisions including
tables and figure.
Declaration of interest
None declared.
LIA in hip and knee arthroplasty
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Handling editor: J. G. Hardman