The Journal of Arthroplasty 36 (2021) 2227e2238

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The Journal of Arthroplasty

j o ur n a l h o me p a g e : w w w . ar t h ro p l a s t y j o u r n a l . o r g

Systematic Review & Meta-Analysis

Simultaneous Bilateral Total Knee Arthroplasty Is Associated With

Shorter Length of Stay but Increased Mortality Compared With
Staged Bilateral Total Knee Arthroplasty: A Systematic Review and
Meta-Analysis
Navnit S. Makaram, MSc, MRCS (Ed) a, b, *, Simon B. Roberts, PhD, FRCS (Tr & Orth) b,
Gavin J. Macpherson, FRCS (Tr & Orth) a
a
Department of Orthopaedics and Trauma, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
b
Department of Orthopaedics and Trauma, The University of Edinburgh, Edinburgh, United Kingdom

a r t i c l e i n f o a b s t r a c t

Article history: Background: Primary total knee arthroplasty (TKA) is associated with high patient satisfaction. However,
Received 23 September 2020 controversy remains regarding the safety and efficacy of conducting simultaneous bilateral (simBTKA)
Received in revised form versus staged bilateral TKA (staBTKA). The objective of this systematic review and meta-analysis was to
27 December 2020
evaluate the current evidence for simBTKA versus staBTKA and compare clinical outcomes including
Accepted 18 January 2021
mortality, complications and length of stay (LOS).
Available online 23 January 2021
Methods: A search was performed of PubMed, MEDLINE, EMBASE and Cochrane central databases be-
tween January 2000 and March 2020. Search terms included “simultaneous,” “staged,” and “bilateral
Keywords:
arthroplasty
TKA.” Inclusion criteria comprised studies comparing outcomes of simBTKA versus staBTKA. Quality of
outcomes included studies was assessed and meta-analyses of pooled data was conducted.
knee Results: 29 articles published between 2001 and 2020 were included in qualitative synthesis from 927
survivorship potentially relevant titles, comprising 257,284 patients. 104,207 patients underwent simBTKA and
loosening 153,632 patients underwent staBTKA. simBTKA was associated with significantly increased 90-day
mortality rate (P < .00001, OR 2.24, 95% CI 1.79-2.81), increased incidence of pulmonary embolism (P
< .00001, OR 1.69, 95% CI 1.51-1.89), venous thrombosis (P < .00001, OR 1.33, 95% CI 1.23-1.43), and
neurological complications (P ¼ .002, OR 1.42, 95% CI 1.13-1.77). Incidence of superficial and deep
infection was significantly increased with staBTKA (P ¼ .02, P < .00001 respectively). Revision rate within
one year was equivocal. Mean LOS was 2.1 days shorter for simBTKA.
Conclusion: SimBTKA was associated with decreased incidence of infection and LOS but increased inci-
dence of 90-day mortality, venous thromboembolism and neurological complications. Revision rates
were equivocal. Patients should be selected and counseled based on the risks respective to each strategy.
© 2021 Elsevier Inc. All rights reserved.

Total knee arthroplasty (TKA) is one the most commonly per-

Funding: This research did not receive any specific grant from funding agencies in
the public, commercial, or not-for-profit sectors.
One or more of the authors of this paper have disclosed potential or pertinent
conflicts of interest, which may include receipt of payment, either direct or indirect,
institutional support, or association with an entity in the biomedical field which
may be perceived to have potential conflict of interest with this work. For full
disclosure statements refer to https://doi.org/10.1016/j.arth.2021.01.045.
* Reprint requests: Navnit S. Makaram, MSc, MRCS (Ed), Department of Ortho-
paedics, The University of Edinburgh, Little France Crescent, Edinburgh, United
Kingdom.
formed orthopedic operations. In 2018, 99,093 total knee arthro-
plasties were performed in the United Kingdom [1]. In the United
States, recent projections have predicted that in 2020, 1,065,000
primary TKAs will require to be performed, with this estimate ris-
ing to 3,416,000 primary TKAs being required to be performed by
2040 [2].
TKA is highly effective in relieving pain and restoring function in
patients with severe osteoarthritis (OA) of the knee [3]. The most
common indication for primary TKA is OA, with the burden of de-
mand increasing with ageing populations. Nearly half of all adults
are clinically diagnosed with osteoarthritis before the age of 85 [4].

https://doi.org/10.1016/j.arth.2021.01.045
0883-5403/© 2021 Elsevier Inc. All rights reserved.
2228 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238
Bilateral symptoms are present in one-third of patients with
knee OA at initial clinical presentation [5]. 40% of patients under-
going unilateral TKA proceed to contralateral TKA within eight
years [6].
It has been estimated that an uncomplicated primary TKR in a
patient costs £5,422, including inpatient stay and ward care
amounting to 16.8% of the cost per TKR [7]. Perioperative care
therefore comprises a significant proportion of the overall cost for
each TKR. Strategies that safely reduce length-of-stay for patients
undergoing bilateral TKA have the potential to improve the cost-
effectiveness of the procedures.
Given the need for an efficient and effective strategy to manage
current demand, and the high incidence of bilateral knee OA
requiring arthroplasty, the safety and effectiveness of simultaneous
bilateral (simBTKA) over staged bilateral (simBTKA) total knee
arthroplasty needs to be evaluated. SimBTKA is defined as bilateral
TKA being performed under the same anesthetic, whilst staBTKA
involves two unilateral TKAs being performed under separate an-
aesthetics, most commonly defined as within one year of each
other.
There is no consensus in the literature as to whether simBTKA or
staBTKA is safer, more effective, or more cost-efficient. SimBTKA
has previously been described as a safe and efficient strategy for
patients with bilateral symptoms, associated with higher patient
satisfaction, shorter length of hospital stay and lower costs to an
institution [8e11].
The primary aim of this systematic review and meta-analysis is
to compare clinical outcomes, including medical and surgical
complications, between patients undergoing simBTKA and
staBTKA. The secondary aim is to compare length of stay between
patients undergoing simBTKA and staBTKA.
Patients and Methods
The literature search was performed in line with the Preferred
Reporting Items for Systematic Review and Meta-Analysis state-
ment [12]. The study is registered with PROSPERO (International
Prospective Register of Systematic Reviews (CRD42020204073).
PubMed, MEDLINE, EMBASE and Cochrane central databases were
searched to identify all studies published between January 2000
and March 2020 that evaluated the outcome of patients undergoing
simBTKA or staBTKA. The following Medical Subject Headings
(MeSH) and terms were used in our search strategy; “bilateral” AND
“simultaneous” OR “staged” AND “total knee arthroplasty” OR
“total knee replacement.” Studies were limited to English language.
Inclusion criteria comprised studies comparing primary
simBTKA with staBTKA, studies reporting clinical outcomes
following simBTKA or staBTKA (pulmonary embolism (PE), deep
vein thrombosis (DVT), revision rate, mortality, cardiorespiratory/
neurological/infective (superficial or deep) complications, studies
evaluating cost effectiveness of simBTKA or staBKTA and studies
reporting biochemical or objective markers associated with
simBTKA or staBTKA such as blood loss, transfusion, anesthetic or
operative duration, and length of stay. Exclusion criteria comprised
studies written in a primary language other than English, studies
comparing bilateral TKA to unilateral TKA only, studies assessing
unilateral TKA only, studies including any knee arthroplasties other
than primary TKA (unicondylar, resurfacing, revision), studies
assessing cost as the only outcome and studies assessing bilateral
TKA that are non-comparative. Studies prior to 2000 were excluded
in order to ensure that only contemporary techniques and implants
were included.
All abstracts identified in the initial search were assessed
independently by two individuals (XX and XX) to identify studies
that met the inclusion criteria. Potentially relevant articles were
reviewed by two authors (XX, XX). Any disagreements were
resolved by consensus with the third author (XX). Further relevant
articles were identified by manual screening of included article
reference lists.
Data from included studies were extracted independently by
two authors and entered into Review Manager software (Version
5.2; The Cochrane Collaboration, The Nordic Cochrane Center,
Copenhagen). The systematic search was completed on July
10, 2020.
Retrieved data included number of patients and patient de-
mographics. The primary clinical outcomes of interest included
mortality (within 90 days), and complication rates including PE/
DVT, cardiac or neurological events, and superficial or deep infec-
tion. Other outcomes assessed included blood loss, rate of trans-
fusion, reoperation and revision rate, length of inpatient stay and
anesthetic/operative duration.
The quality of the included studies was assessed by two authors
(NSM and SBR) using the Newcastle-Ottawa Scale (NOS) [13]. The
scores of items identifying study quality varied from 0 to 9. The
study was considered as high quality when it was awarded 7 or
more stars, moderate when 4-6 stars, and poor when 0-3 stars. Any
disagreements of data recording and conflicting scores were
resolved by the third author (GJM).
Statistical Analysis
Odds ratios (ORs) and 95% confidence intervals (CIs) were
calculated for dichotomous outcomes. For pooled continuous data
for outcomes measured in scales, the standardised mean difference
(SMD) and 95% CIs were calculated. The I2 statistics were used as a
quantitative measure of heterogeneity, with I2 >50% indicating
significant inconsistency; heterogeneity was not detected unless
specifically reported. A random effects model was adopted to
calculate pooled ORs in the case of significant heterogeneity (P < .10
or I2>50%) [14,15] otherwise, a fixed-effects model was used.
Sensitivity analysis was conducted if permissible by systematic
removal of each included article to assess measures of heteroge-
neity. Forest plots were used to graphically present the results of
individual studies and the respective pooled estimate of effect size.
All statistical analyses were performed with Review Manager
(Version 5.2; The Cochrane Collaboration, The Nordic Cochrane
Center, Copenhagen).
Results
Literature Search
The literature search identified 927 potentially relevant studies;
29 studies met inclusion criteria and were included in final quali-
tative and quantitative analysis (Fig. 1) [10,16e43]. The 29 included
studies comprised 257,284 participants, of which 104,207 patients
underwent simBTKA and 153,632 patients underwent staBTKA. Of
the 29 included studies, two were prospective, and 27 were
retrospective. Summary characteristics of the 29 included studies
are shown in Table 1.
Methodological Quality Assessment
Quality assessment was performed with the NOS. 16 studies
[10,16,18,21e23,25,27,28,30,32,33,35,36,38,41] were considered of
high quality, and 13 were considered of moderate quality
[17,19,20,24,26,29,31,34,37,39,40,42,43]. Most studies did not
report on adequacy of follow up or failed to achieve >90% follow-
up. Thirteen studies [19,20,24,26,29,31,34,37,39e43] did not
assess selection bias or confounding factors when evaluating
 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238
Fig. 1. PRISMA flowchart for literature search of studies. uniTKAeunilateral total knee arthroplasty. SBTKAesimultaneous or staged bilateral total knee arthroplasty.
differences in complication rates between StaBTKA and SimBTKA
groups. A summary of the quality assessments of the included
studies is shown in Table 2.
Primary aim: Clinical Outcomes
Clinical outcomes assessed included mortality, medical com-
plications (comprising neurological complications, venous throm-
boembolism and cardiac complications), and surgical
complications (comprising superficial & deep infection, and revi-
sion arthroplasty).
Mortality
23 studies [16e19,21,22,24e33,35e37,39,40,42,43] were
included for analysis of mortality. These comprised 87,386 patients
undergoing simBTKA and 136,062 patients undergoing staBTKA.
Mortality was reported within 90 days post-operatively in these
studies. Mortality was significantly higher in simBTKA patients
compared to staBTKA patients (simBTKA: 0.298%, staBTKA: 0.157%;
P < .00001; Odds ratio (OR) 1.89, 95% Confidence Interval (CI) 1.56-
2.28). There was significant heterogeneity (P ¼ .03, I2 ¼ 44%) in the
combined data; heterogeneity resolved when the study by Meehan
et al [32] was specifically removed (P ¼ .18, I2 ¼ 23%), resulting in
75,941 patients included in the simBTKA cohort and 109,712 pa-
tients in the staBTKA cohort following sensitivity analysis (Fig. 2).
The significantly higher risk of mortality in simBTKA patients was
2229
also maintained after correcting for heterogeneity (simBTKA:
0.286%, staBTKA: 0.118%; P < .00001, OR 2.24, 95% CI 1.79-2.81).
Neurological Complications
Data regarding neurological complications was available for
rates of cerebrovascular accident and confusion from twelve
studies (46,094 simBTKA patients; 81,725 staBTKA patients)
[16,18,19,23,25,28,32,33,35,36,40,42]. Neurological complications
were significantly more common in simBTKA patients compared to
staBTKA patients (simBTKA: 0.349%, staBTKA: 0.219%; P ¼ .002, OR
1.42, 95% CI 1.13-1.77) (Fig. 3).
Pulmonary Embolism
The incidence of pulmonary embolism 30 days following pri-
mary arthroplasty was specifically reported in 16 studies (61,637
simBTKA patients; 120,720 staBTKA patients)
[10,18,23e29,31e34,36,39,40]. The incidence of pulmonary embo-
lism following primary arthroplasty was significantly greater in
simBTKA patients compared to staBTKA patients (simBTKA: 1.04%,
staBTKA: 0.716%; P < .00001 OR 1.45, 95% CI 0.82-1.80) (Fig. 4).
There was significant heterogeneity (P < .00004, I2 ¼ 79%) in the
pooled data; a significantly higher risk of pulmonary embolism in
simBTKA compared to staBTKA patients was maintained after
correction for heterogeneity by specific exclusion of the study by
2230 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238

Table 1
Summary of Studies Included in Meta-Analysis.

Author Year Country Journal Study Design SimBTKA StaBTKA

N (n) % Female Mean Age N (n) % Female Mean Age Time Interval Between
(%) (years) (%) (years) Stages (months)

Gill 2020 Australia ANZ J Surg Retrospective 122 62.3 70.6 46 50 70.7 7.93
Richardson 2019 USA Knee Retrospective 1637 55.8 n/a 6110 n/a n/a <12
Tsay 2019 USA J Arthroplasty Retrospective 27,301 56.8 65.8 45,419 62.6 66.6 6.03
Wyles 2019 USA J Arthroplasty Retrospective 188 58.0 61 242 64 72 <12
Wyatt 2019 New Zealand ANZ J Surg Retrospective 6440 38.7 n/a 5116 50.7 n/a <12
Koh 2018 S Korea JBJS Am Retrospective 820 95.9 68.6 633 95.9 69.7 <12
Chua 2018 Australia J Arthroplasty Retrospective 23,136 46.2 n/a 12,951 49.4 n/a <6
Sobh 2018 USA J Arthroplasty Retrospective 225 52 61 337 62 68 <12
Seol 2016 S Korea J Orthop Sci Retrospective 759 94.3 68.3 315 92.1 66 1.22
Bohm 2016 Canada Acta Orthop Retrospective 6349 59 64 25,253 61 66 <12
Sheth 2016 USA J Arthroplasty Retrospective 2814 57.2 64.8 5177 63.1 67.4 <12
Lindberg-Larsen 2015 Denmark KSSTA Retrospective 157 52.9 64 628 57.1 66 <12
Niki 2014 Japan J Arthroplasty Prospective 60 83.3 73 60 83.3 72.3 8.2
Courtney 2014 USA J Arthroplasty Retrospective 103 63 59.4 131 77 64.2 0.23
Bini 2014 USA J Arthroplasty Retrospective 1230 58.4 66 2123 65.8 67 <12
Poultsides 2013 USA J Arthroplasty Retrospective 2825 62.4 65.2 1151 67.8 69.5 6.99
Bolognesi 2013 USA J Arthroplasty Retrospective 4519 59 73.3 3788 61.3 67.7 <12
Meehan 2011 USA JBJS Am Retrospective 11,445 53.9 67.2 23,715 61.3 67.7 <12
Yoon 2010 S Korea J Arthroplasty Retrospective 119 94.1 70 119 94.1 70 12
Hooper 2009 New Zealand J Arthroplasty Retrospective 1012 n/a 65 1360 n/a 69 <12
Stefansdottir 2008 Sweden CORR Retrospective 1139 59.2 70.4 3432 62.5 71.2 <12
Forster 2006 Australia BJJ Retrospective 28 46.4 66 36 50 68 0.23
Walmsley 2006 UK Knee Retrospective 826 n/a n/a 1796 n/a n/a <12
Barrett 2006 USA JBJS Am Retrospective 8324 57.8 n/a 13,039 62.9 n/a <12
Hutchinson 2006 Australia BJJ Prospective 438 44 67 125 63 65 34
Sliva 2005 USA JBJS Am Retrospective 26 46 59.3 306 65.4 67.2 17.6
Stubbs 2005 Australia ANZ J Surg Retrospective 61 n/a 64 38 n/a 67 <12
Ritter 2003 USA JBJS Am Retrospective 2050 55.8 69.9 152 77.0 69.2 16.8
Mangaleshkar 2001 UK Knee Retrospective 54 61.1 73 34 61.7 71.7 <12
Total 104,207 60.5 66.5 153,632 66.4 68.3

The included studies, study characteristics and basic demographics of patients in both simultaneous bilateral total knee arthroplasty (simBTKA) cohort and staged bilateral
total knee arthroplasty (staBTKA) cohort in each study are displayed. The time interval between first and second stages in staBTKA is displayed, a median value is given where
possible. The total number of patients, mean age, and gender balance (mean proportion Female (%)) of all participants is provided in the bottom row.
N/a, not available/not reported.

Bohm et al [24] (simBTKA: 1.13%, staBTKA: 0.667%; P < .00001, OR
1.69, 95% CI 1.51-1.89).
Deep Vein Thrombosis
The incidence of deep vein thrombosis (DVT) was specifically
reported in 15 studies (50,352 simBTKA patients; 86,480 staBTKA
patients) [10,18,19,23,25e29,31e34,39,40]. The incidence of DVT
following primary knee arthroplasty procedures was significantly
greater in simBTKA compared to staBTKA patients (simBTKA:
2.53%, staBTKA: 1.79%; P < .00001, OR 1.33, 95% CI 1.23-1.43) (Fig. 5).
Cardiac Complications
The incidence of cardiac complications following primary knee
arthroplasty procedures was specifically reported by 15 studies (58,920
simBTKA patients; 117,270 staBTKA patients)
[16e18,23e26,28,31,32,35,39e42]. There was significant heterogene-
ity (P < .00001, I2 ¼ 73%) in the pooled data from these studies, which
was not corrected by sensitivity analysis. A random effects model was
therefore used for this analysis; no significant difference was observed
in cardiac complications between simBTKA and staBTKA (simBTKA:
1.71%, staBTKA: 1.58%; P ¼ .41, OR 0.90, 95% CI 0.70-1.15) (Fig. 6).
Richardson et al [17], Bohm et al [24] and Chua et al [22] reported
the complication “infection” but did not differentiate between su-
perficial or deep, and these were therefore excluded from our
analysis of superficial and deep infection rates. The incidence of
superficial infection following primary arthroplasty was signifi-
cantly greater in staBTKA patients compared to simBTKA (P ¼ .004).
There was significant heterogeneity (P ¼ .07, I2 ¼ 40%) in the
combined data; A significantly higher risk of superficial infection in
staBTKA compared to simBTKA patients was maintained after
correction for heterogeneity (P ¼ .25, I2 ¼ 20%) by specific exclusion
of the study by Seol et al [23] (simBTKA: 0.305%, staBTKA: 0.365%,
P ¼ .02, OR 0.79 95% CI 0.65-0.97) (Fig. 7).
Deep Infection
Incidence of deep infection was reported in 15 studies
[10,16,18e20,23,26,29e34,39,42] (52,390 simBTKA patients; 82,155
staBTKA). Gill et al [16], Wyatt et al [20], Wyles et al [19] and Yoon
et al [33] recorded no deep infections in either simBTKA or staBTKA
cohorts. The incidence of deep infection following primary knee
arthroplasty was significantly greater in staBTKA patients
compared to simBTKA patients (simBTKA: 0.859%, staBTKA: 1.38%,
P < .00001, OR 0.61 95% CI 0.54-0.68) (Fig. 8).

Superficial Infection Revision Arthroplasty

Incidence of superficial infection was reported in 13 studies Ten studies [10,19,20,22,24,25,29,31,33,39] were included for
(51,952 simBTKA patients; 82,026 staBTKA patients) analysis of revision rate (50,510 simBTKA patients; 86,798 staBTKA
[10,16,18,19,23,26,29e34,42]. Studies by Courtney et al [28], patients). Revision rates at one year following primary arthroplasty
 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238 2231

Table 2
Quality Assessment of Included Studies Using the Newcastle-Ottawa Scale (NOS).

Study Author (year) Selection Comparability Outcome Total

Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8

Gill (2020) [16] 1 1 1 1 1 1 1 0 7

Richardson (2019) [17] 1 1 1 1 1 1 0 0 6
Tsay (2019) [18] 1 1 1 1 1 1 1 0 7
Wyles (2019) [19] 1 0 1 1 0 1 1 1 6
Wyatt (2019) [20] 1 1 1 1 0 1 1 0 6
Koh (2018) [21] 1 1 1 1 2 1 1 0 8
Chua (2018) [22] 1 1 1 1 1 1 1 0 7
Sobh (2018) [10] 1 1 1 1 2 1 1 0 8
Seol (2016) [23] 1 1 1 1 1 1 1 0 7
Bohm (2016) [24] 1 1 1 1 0 1 1 0 6
Sheth (2016) [25] 1 1 1 1 2 1 1 0 8
Lindberg-Larsen (2015) [26] 1 1 1 1 0 1 1 0 6
Niki (2014) [27] 1 1 1 1 1 1 1 0 7
Courtney (2014) [28] 1 1 1 1 1 1 1 0 7
Bini (2014) [29] 1 1 1 1 0 1 1 0 6
Poultsides (2013) [30] 1 1 1 1 2 1 1 0 8
Bolognesi (2013) [31] 1 1 1 1 0 1 1 0 6
Meehan (2011) [32] 1 1 1 1 2 1 1 0 8
Yoon (2010) [33] 1 1 1 1 2 1 0 0 7
Hooper (2009) [34] 1 1 1 1 0 1 1 0 6
Stefansdottir (2008) [35] 1 1 1 1 1 1 1 0 7
Forster (2006) [36] 1 1 1 1 1 1 1 0 7
Walmsley (2006) [37] 1 1 1 1 0 1 1 0 6
Barrett (2006) [38] 1 1 1 1 1 1 1 0 7
Hutchinson (2005) [39] 1 1 1 1 0 1 1 0 6
Sliva (2005) [40] 1 1 1 1 0 1 1 0 6
Stubbs (2005) [41] 1 1 1 1 0 1 1 1 7
Ritter (2003) [42] 1 1 1 1 0 1 1 0 6
Mangaleshkar (2001) [43] 1 1 1 1 0 1 1 0 6

Categories include: Selection (four itemseQ1. Q2. Q3. Q4.) Comparability of cohorts (one itemeQ5.), and assessment of outcome (three itemseQ6. Q7. Q8.) Each Q can be
awarded a maximum of one star, with the exception of Q5 where a maximum of two stars can be awarded). The study was considered high quality when it was awarded 7 or
more stars (green), moderate when 4-6 stars (yellow), and poor when 0-3 stars (red).

were used for analysis. There was no significant difference in inci- Secondary Aim: Length of Stay
dence of revision arthroplasty between simBTKA and staBTKA pa-
tients at one year following primary arthroplasty (simBTKA: 2.95%, Due to the variability in the method of reporting results (range
staBTKA 2.05%; P ¼ .27, OR 1.04, 95% CI 0.97-1.13) (Fig. 9). vs standard deviation and median vs mean), a pooled meta-

Fig. 2. 90 day mortality rate. Forest plot displaying incidence of 30-90 day mortality in patients undergoing simultaneous (sim BTKA) and staged (staged BTKA) bilateral total knee
arthroplasty procedures. Fixed effect model.
2232 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238

Fig. 3. Incidence of neurological complications. Forest plot displaying the incidence of neurological complications in patients undergoing simultaneous (sim BTKA) compared to
staged (staged BTKA) bilateral total knee arthroplasty. Fixed effect model.

analysis of included studies for length of stay (LOS) could not be
performed. However, average LOS was reported in 12 included
studies, comprising 16,076 patients in the simBTKA cohort and
32,686 patients in the staBTKA cohort. Average LOS in the
simBTKA cohort was 6.5 days, and in the staBTKA cohort was 8.6
days, when LOS for both stages of BTKA were taken in total. Thus,
mean LOS in the simBTKA cohort was 2.1 days shorter than the
staBTKA cohort.
Due to the changes in standards of practice over recent years
resulting in a possible shorter length of stay for both simBTKA and
staBTKA, a subset analysis was performed of all studies published
from 2015 onwards. Again, due to variability in method of
reporting, a meta-analysis was not able to be performed of this
subset. Of the 12 studies published from 2015 onwards, six studies
reported LOS (comprising 8395 patients in the simBTKA cohort
and 27,117 patients in the staBTKA cohort) (Table 3). Average LOS
in the simBTKA cohort was 7.99 days, and in the staBTKA cohort
was 8.65 days, skewed markedly by studies published from East
Asia.
A further subset analysis was performed based on geographic
source of study, reflecting the influence of various healthcare sys-
tems on LOS (Table 4). A marked difference was noted in average
LOS based on geographical source of study, with studies from
Europe and North America having shortest LOS for both simBTKA
and staBTKA, and studies from East Asia having the longest overall
LOS.
Overall, all regions reported a decreased LOS with simBTKA
compared with staBTKA.
Discussion
The primary aim of this systematic review and meta-analysis
was to compare clinical outcomes, including mortality, medical
and surgical complications, between patients undergoing simBTKA
and staBTKA. The secondary aim was to compare length of stay
between patients undergoing simBTKA and staBTKA. This review
included 29 studies published between 2000 and 2020, most of
which were retrospective cohort studies (Table 1). The results of
this meta-analysis indicate that simBTKA is associated with a
decreased rate of infection and reduced length of stay, but
increased mortality and rates of venous thromboembolism and
neurological complications. Early revision rates were found to be
equivalent between groups.
Mortality
We identified that staBTKA was associated with a significantly
reduced risk of mortality (within 90 days’ post-operatively)

Fig. 4. Incidence of pulmonary embolism. Forest plot displaying the incidence of pulmonary embolism in patients undergoing simultaneous (sim BTKA) and staged (staged BTKA)
bilateral total knee arthroplasty procedures. Fixed effect model.
 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238 2233

Fig. 5. Incidence of deep vein thrombosis. Forest plot displaying the incidence of deep vein thrombosis in patients undergoing simultaneous (sim BTKA) and staged (staged BTKA)
bilateral total knee arthroplasty procedures. Fixed effect model.

compared to simBTKA (Fig. 2). Mortality within 90 days of surgery
was analyzed as this was the most common postoperative time
interval for assessment of mortality amongst the included studies.
SimBTKA appears to confer an additional risk of significant
adverse events, perhaps due to the greater magnitude of the
surgery. Our results should be interpreted with caution; patients
undergoing staBTKA who die following the first TKA may be
recorded as unilateral TKA, and thereby underestimate the mor-
tality rate associated with staBTKA. Similarly, patients undergoing
staBTKA who sustain serious complications following their first
TKA may be withdrawn from, or not proceed to, the second of
their staged TKA procedures. Thus, there is risk of both reporting
and selection bias when assessing mortality rates for staBTKA
compared to simBTKA.
Our finding that simBTKA was associated with a significantly
increased mortality rate compared to staBTKA is consistent with
recent meta-analyses from Fu et al [44] and Hussain et al [45],
which included studies published between 1978-2011. Our mor-
tality results for simBTKA and staBTKA confirm the findings from
historical analyses, using data from more contemporary studies and
a substantially larger pooled sample size.
Neurological Complications
The incidence of neurological complications (primarily stroke
and post-operative confusion), was significantly greater in simBTKA
patients (Fig. 3). SimBTKA involves a longer duration of surgery and
anesthesia, which may predispose to increased rate of neurological
complications. This finding should be interpreted with caution, as
the definition of “neurological complications” was poorly specified
in the vast majority of studies included in our analysis.
Venous Thromboembolism
The incidence of both pulmonary embolism (PE) and deep
venous thrombosis (DVT) was significantly higher in simBTKA pa-
tients compared to staBTKA patients (Figs. 4 and 5). For PE, the
pooled data showed high initial heterogeneity, which resolved
when the study by Bohm et al [24] was removed. In this study the
incidence of PE was recorded if present at least once in the staged
procedure, thus if a patient sustained a PE at both the first stage and
the second stage of a staBTKA procedure, this would be counted as

Fig. 6. Incidence of cardiac complications. Forest plot displaying the incidence of cardiac complications in patients undergoing simultaneous (sim BTKA) and staged (staged BTKA)
bilateral total knee arthroplasty procedures using a Random Effects model given no resolution of heterogeneity on sensitivity analysis.
2234 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238

Fig. 7. Incidence of superficial infection. Forest plot displaying the incidence of superficial infection in patients undergoing simultaneous (sim BTKA) and staged (staged BTKA)
bilateral total knee arthroplasty procedures. Fixed effect model.

one complication. This variation in recording may account the
heterogeneity observed.
The findings of our meta-analysis are consistent with previous
results [44,46]. Previous studies demonstrated an increased inci-
dence of PE in patients undergoing simBTKA. The requirement for
two pressurised cementing episodes under one anesthetic in
simBTKA compared with staBTKA is a theoretical increased risk for
PE, and may explain the increased incidence in simBTKA [47].
Increased DVT incidence in the simBTKA cohort may be due to the
prolonged duration of the single procedure, or the prolonged
rehabilitation and mobilisation associated with having both knees
replaced simultaneously. We recognise concerns associated with
the combination of bilateral sequential tourniquet use and the use
of bilateral intramedullary rods for intramedullary referencing,
with a theoretically increased risk of fat embolism. However, with
the advent of tourniquet free total knee arthroplasty, contemporary
thromboprophylactic measures such as modern antithrombotic
therapies, intermittent pneumatic compression devices and
enhanced recovery protocols, the increased risk of thromboembo-
lism and fat embolism may be mitigated [48].
Cardiac Complications
There was no significant difference in incidence of cardiac
complications between patients undergoing simBTKA and staBTKA
(Fig. 6). Previous studies have reported conflicting results in
regarding the incidence of cardiac complications following
simBTKA and staBTKA. Several studies have identified a signifi-
cantly increased incidence of cardiac complications in simBTKA
***[49e51]. However, results from recent meta-analyses are
consistent with our finding of no significant difference in incidence
of cardiac complications between simBTKA and staBTKA cohorts.
Superficial and Deep Infection
13 studies [10,16,18,19,23,26,29e34,42] reported incidence of su-
perficial infection, and 15 studies [10,16,18e20,23,26,29e34,39,42]
reported on deep infection. Four studies did not report whether
infection was superficial or deep [17,22,24,28]. We identified a
significantly increased incidence of superficial infection in patients
undergoing staBTKA compared with simBTKA (Fig. 7). The study by

Fig. 8. Incidence of deep infection. Forest plot displaying the incidence of deep infection in patients undergoing simultaneous (sim BTKA) and staged (staged BTKA) bilateral total
knee arthroplasty procedures. Fixed effect model.
 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238 2235

Fig. 9. Incidence of revision arthroplasty. Forest plot displaying the incidence of revision surgery in patients undergoing simultaneous (sim BTKA) compared to staged (staged BTKA)
bilateral total knee arthroplasty. Fixed effect model.

Seol et al [23] was deleted as part of a sensitivity analysis due to high
initial heterogeneity. We explored potential sources of bias in this
study which could account for heterogeneity. There was no definition
of superficial infection described in this study, which could account
for variation in severity of infection being included as superficial
infection, including that requiring only medical intervention in
addition to infections requiring surgical debridement.
The incidence of deep infection was similarly significantly
higher in patients that underwent staBTKA compared with those
who underwent simBTKA (Fig. 8). Our findings are consistent with
results from both Fu et al [44] and Lui et al [46], which identified an
increased incidence of superficial and deep infection following
staBTKA compared to simBTKA. Selection bias may influence rates
of infection with each strategy, as younger, healthier patients are
more likely to be considered for simBTKA and may be less sus-
ceptible to infection [52e54]. Second, staBTKA has been shown by
our study to involve an increased length of hospital stay (LOS)
compared with simBTKA [19,21,23,26,28,30,31,33,36,44]. Poult-
sides et al [30] reported that longer LOS was an independent risk
factor for development of infection even after adjusting for con-
founding variables. It is hypothesised that longer LOS exposes pa-
tients to a greater risk of nosocomial pathogens that could result in
superficial or deep infection [55]. It may be that increased incidence
of infection in staBTKA is due to the number of times that a patient
undergoing TKA enters and leaves the operating room, with the
associated exposure that this entails [55].
Early Revision Rate
No significant difference was observed in revision rate at one-
year postoperatively, between simBTKA and staBTKA patients
(Fig. 9). Variability in definition of revision and data collection
methods between studies and institutions may limit the strength of
this observation. A prior meta-anlaysis [44] has observed a signif-
icantly lower revision rate in simBTKA, and concluded that this was
as a result of the significantly increased rate of deep infection
associated with staBTKA requiring revision in their analysis.
Currently there is no consensus in the literature on the influence of
simBTKA and staBTKA on revision rates following TKA.
Length of Stay (LOS)
Mean LOS for simBTKA patients was 2.1 days less than for
staBTKA patients. There is limited data from previous meta-
analyses regarding LOS for simBTKA and staBTKA. The pooled
data suggests acute hospital LOS is markedly shorter in simBTKA,
and this is associated with a lower total cost for inpatient care for
simBTKA compared to staBTKA. StaBTKA also incurs the cost of two
separate preadmission episodes, two acute hospital admissions,
two anaesthetics, and two periods of rehabilitation. Due to limited
number of studies reporting cost of simBTKA and staBTKA, a formal
meta-analysis of cost was not performed. Individual studies have
previously reported that the markedly reduced LOS in simBTKA
results in significant cost savings compared to staBTKA
[10,16,19,41]. Gill et al [16] reported a cost saving per patient un-
dergoing simBTKA of $6388 compared with staBTKA, and Wyles
et al [19] showed a cost saving of 50% per patient with simBTKA
compared with staBTKA. The current literature favors simBTKA as
the more cost effective approach compared with staBTKA. How-
ever, few studies include prospective matched cohorts, and the
majority of studies retrieve cost data from national databases of
insurance related claims.
There is a noted variation in LOS based on healthcare system and
geographical region, as noted by Table 4, which introduced a

Table 3
Summary of Length of Stay Data Reported by Subset of Studies Published From 2015.

Author Year Country Journal Study Design SimBTKA StaBTKA

N (n) Length of Stay (days) (median) N (n) Length of Stay (days) (Median)

Gill 2020 Australia ANZ J Surg Retrospective 122 7 46 12

Wyles 2019 USA J Arthroplasty Retrospective 188 3 242 6
Koh 2018 S Korea JBJS Am Retrospective 820 16.2 (mean) 633 25.4 (mean)
Seol 2016 S Korea J Orthop Sci Retrospective 759 18 (mean) 315 34.1 (mean)
Bohm 2016 Canada Acta Orthop Retrospective 6349 6 25,253 8
Lindberg-Larsen 2015 Denmark KSSTA Retrospective 157 4 628 6
Overall 8395 7.99 27,117 8.65

The included studies, study characteristics and number of patients in both simultaneous bilateral total knee arthroplasty (simBTKA) cohort and staged bilateral total knee
arthroplasty (staBTKA) cohort in each study are displayed. The median length of inpatient hospital stay (LOS) is displayed. The mean value is displayed if median was not
reported. An overall average LOS is displayed for both simBTKA and staBTKA.
2236 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238

Table 4
Summary of Studies Reporting Length of Stay According to Geographical Source of Study.

Region (Author) Year Country Journal Study Design SimBTKA StaBTKA

N (n) Length of Stay (days) (median) N (n) Length of Stay (days) (Median)

North America
Wyles 2019 USA J Arthroplasty Retrospective 188 3 242 6
Bohm 2016 Canada Acta Orthop Retrospective 6349 6 25,253 8
Courtney 2014 USA J Arthroplasty Retrospective 103 3.8 131 7.2
Poultsides 2013 USA J Arthroplasty Retrospective 2825 5.5 1151 9.5
Bolognesi 2013 USA J Arthroplasty Retrospective 4519 4.4 3788 7.6
Sliva 2005 USA JBJS Am Retrospective 26 5 306 9
Overall 14,010 5.32 30,871 8.00
Australasia
Gill 2020 Australia ANZ J Surg Retrospective 122 7 46 12
Forster 2006 Australia BJJ Retrospective 28 11 36 15
Stubbs 2005 Australia ANZ J Surg Retrospective 61 11 38 16
Overall 211 8.69 120 14.2
East Asia
Koh 2018 S Korea JBJS Am Retrospective 820 16.2 633 25.4
Seol 2016 S Korea J Orthop Sci Retrospective 759 18 315 34.1
Yoon 2010 S Korea J Arthroplasty Retrospective 119 7.5 119 11.7
Overall 1698 16.4 1067 26.4
Europe
Lindberg- Larsen 2015 Denmark KSSTA Retrospective 157 4 628 6
Overall 157 4.00 628 6.00

The included studies, study characteristics including country in which study was conducted, and number of patients in both simultaneous bilateral total knee arthroplasty
(simBTKA) cohort and staged bilateral total knee arthroplasty (staBTKA) cohort are displayed. Data are Displayed according to region. The median length of inpatient hospital
stay (LOS) is displayed. The mean value is displayed if median was not reported. An overall average LOS is displayed for Both simBTKA and staBTKA, according to region in
which study was conducted.

geographical bias in overall LOS observed. It may be expected that
the recent shift toward enhanced recovery and “outpatient” or
same day TKA, particularly in North America and Europe, would
likely mean a shorter average length of stay would be observed in
current practice of TKA compared with the figures noted in our
meta-analysis. We note however that when only studies published
in North America and Europe, from 2015 onwards were taken into
account, the LOS for simBTKA was 5.9 days and for staBTKA was 7.9
days. It is likely that studies published more recently may include a
greater proportion of patients that have undergone TKA through
such enhanced recovery protocols and therefore have a shorter
overall LOS. Our results should be interpreted with caution; we
note that the vast majority of included studies were retrospective in
nature, and therefore will include a significant proportion of pa-
tients who have undergone TKA prior to modern rehabilitation
protocols, despite the date of publication of these studies being
recent. Thus, the LOS figures reflected by these studies may not
reflect current practice, which is a limitation. There is a need for
prospective studies comparing costs between matched cohorts of
patients undergoing simBTKA compared with staBTKA using a time
driven activity based costing approach [7], to reflect current
enhanced recovery protocols and robustly investigate the true cost
difference of staBTKA and simBTKA when complications, read-
missions and follow-up are taken into account.
Limitations
Our study has strengths and limitations. It is a comprehensive
review and meta-analysis of the relevant peer-reviewed literature
over the last 20 years comprising studies that have assessed clinical
outcomes of patients undergoing simBTKA and staBTKA. By
selecting studies published after 2000 only, we aimed to include
studies performed using modern surgical techniques and during
the era of enhanced recovery protocols.
Based on our results, we recommend that the strategy for per-
forming bilateral TKA should be carefully selected based on patient
age, comorbidity profile and preference. Patients should be care-
fully counseled regarding the respective incidence of complications
and consequent risks associated with each respective strategy.
Younger, fitter patients who have a greater physiological reserve
may benefit from simBTKA due to the more rapid recovery and
reduced LOS, and potentially enabling less time off work if still in
employment.
As previously noted, a limitation of this study is that the results
are drawn from pooling data from studies that were largely retro-
spective in nature. Most of these studies involved unmatched par-
ticipants and reported results not adjusted for confounding
variables; this may influence comparisons across studies due to lack
of information available about pre-operative and post-operative
status for patients in each treatment arm. Varying protocols across
different institutions increases confounding across the pooled re-
sults. There remains a variation in the definition of “staged,”
although most commonly defined as both TKAs being performed
within one year, and there remains a degree of variation in time
intervals between the first and second stage of staBTKA between
studies and patients. The staging of procedures over these intervals
may lead to a variety of confounding factors, such as level of recovery
from the first procedure and relative risk of complications. Further-
more, due to their retrospective design, the majority of included
studies did not account for differences in comorbidity profile be-
tween those undergoing simBTKA and staBTKA, resulting in poten-
tial selection bias, illustrated by our quality assessment. Finally, we
have not considered functional outcome when comparing the out-
comes of simBTKA compared with staBTKA. Further matched pro-
spective studies comparing both clinical outcomes and patient-
reported outcomes following simBTKA and staBTKA are required.
Conclusion
This meta-analysis identified that simBTKA is associated with
decreased rates of infection and reduced length of stay, but
increased rates of mortality, venous thromboembolism and
neurological complications compared to staBTKA. Revision rates
were similar for both approaches. There is a need for high-quality,
prospective studies to better evaluate the clinical, functional and
cost effectiveness of simBTKA compared to staBTKA.
 N.S. Makaram et al. / The Journal of Arthroplasty 36 (2021) 2227e2238 2237

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