- Email: [email protected]
Comparing the 30-Day Risk of Venous Thromboembolism and Bleeding in Simultaneous Bilateral vs Unilateral Total Knee Arthroplasty
Accepted Manuscript Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral versus unilateral total knee arthroplasty Karim Z. Masrouha, MD, Jamal J. Hoballah, MD, Hani Tamim, MPH, PhD, Bernard H. Sagherian, MD PII:
S0883-5403(18)30552-7
DOI:
10.1016/j.arth.2018.06.002
Reference:
YARTH 56659
To appear in:
The Journal of Arthroplasty
Received Date: 15 February 2018 Revised Date:
29 May 2018
Accepted Date: 1 June 2018
Please cite this article as: Masrouha KZ, Hoballah JJ, Tamim H, Sagherian BH, Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral versus unilateral total knee arthroplasty, The Journal of Arthroplasty (2018), doi: 10.1016/j.arth.2018.06.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Original article
RI PT
Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral versus unilateral total knee arthroplasty Karim Z. Masrouha, MD1, Jamal J. Hoballah, MD2, Hani Tamim, MPH, PhD3, Bernard H. Sagherian, MD1
SC
Investigation performed at the Division of Orthopaedic Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon
1
M AN U
Division of Orthopaedic Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon 2
Division of Vascular Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon
3
TE D
Biostatistics Unit in the Clinical Research Institute, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Correspondence and reprints:
AC C
EP
Bernard H. Sagherian, MD Assistant Professor of Orthopaedic Surgery Division of Orthopaedic Surgery Department of Surgery American University of Beirut Medical Center P.O.Box 11-0236 Riad El-Solh Beirut 1107 2020 Lebanon Tel: + 961 (1) 350000, ext 5444 Fax: +961 (1) 363291 Email: [email protected]
ACCEPTED MANUSCRIPT 1 Original article Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral versus unilateral total knee arthroplasty
RI PT
1 2 3 4 5 6 7 8 9
Abstract
Background: Simultaneous bilateral total knee arthroplasty (SBTKA) may offer certain benefits,
11
however its overall safety is still disputed. This study aimed to compare the risk of
12
thromboembolism and bleeding in patients who underwent SBTKA versus unilateral total knee
13
arthroplasty (TKA).
14
Methods: The American College of Surgeons – National Quality Improvement Program (ACS-
15
NSQIP) database from 2008 – 2015 was used to investigate the short-term postoperative
16
complications and their risk factors following SBTKA as compared to unilateral TKA.
17
Demographics, comorbidities, and 30-day outcomes were analyzed. Complications with an
18
increased incidence following SBTKA were stratified to identify subgroups of patients at high
19
risk.
20
Results: Total of 155,022 patients were identified, of which 150,581 underwent unilateral TKA
21
and 4,441 underwent SBTKA. The SBTKA group was found to be at a higher risk for venous
22
thromboembolism (VTE), bleeding, and composite morbidity. Stratification analysis revealed
23
that SBTKA subgroups at higher risk for VTE include patients of black or Asian origin, obese
24
patients and those who underwent anesthesia other than general or spinal / epidural. SBTKA
25
subgroups at higher risk for bleeding include patients older than 85 years, those with race other
26
than white, underweight and obese patients, and patients who underwent anesthesia other than
27
spinal / epidural. Although none of the subgroups were protected from bleeding, patients who
AC C
EP
TE D
M AN U
SC
10
ACCEPTED MANUSCRIPT 2 underwent spinal / epidural anesthesia had a lower risk for bleeding compared to other types of
29
anesthesia.
30
Conclusion: SBTKA confers an increased risk of postoperative VTE, bleeding and composite
31
morbidity at 30 days, with no increase in mortality.
32 33 34
Keywords
35
complications; risk factors
RI PT
28
AC C
EP
TE D
M AN U
SC
Thromboembolism; bleeding; bilateral knee arthroplasty; unilateral knee arthroplasty;
ACCEPTED MANUSCRIPT 3 36
Introduction
37 The safety and cost-effectiveness of simultaneous bilateral total knee arthroplasty (SBTKA)
39
compared to a staged procedure continues to be a matter of debate as evidenced by the number of
40
recent studies published in the literature. There are no level 1 prospective studies addressing this
41
issue and most of the literature relies on single-center retrospective analyses or population-based
42
studies which have shown that SBTKA decreases costs but may increase perioperative morbidity
43
and mortality [1-9]. However, not all studies have looked into specific morbidities nor have they
44
attempted to identify subgroups of patients that might be at increased risk for specific
45
complications when undergoing SBTKA compared to a unilateral procedure[10-15] .
46
The American College of Surgeons – National Surgical Quality Improvement Program (ACS-
47
NSQIP) dataset has been used to better understand the 30-day outcomes of surgical procedures
48
and help participating hospitals identify perioperative risk factors and develop guidelines to
49
decrease the rate of complications and adverse events[16]. It has recently been used to look into
50
outcomes following SBTKA as compared to unilateral TKA [10, 11]. These studies have
51
analyzed overall and major complications as well as 30-day readmission rates and mortality as
52
outcomes. They have either failed to show an increased risk of thromboembolism and bleeding
53
in patients undergoing SBTKA versus unilateral TKA [11] or have not specifically analyzed
54
these complications[10]. Moreover they have not attempted stratification of specific
55
complications to identify subgroups of patients within the SBTKA group who might be at even
56
higher risk for specific complications compared to the unilateral TKA group. Rather they have
57
grouped all the complications and analyzed independent predictors on major complications. We
58
therefore sought to use the ACS-NSQIP database to analyze specific complications for which
AC C
EP
TE D
M AN U
SC
RI PT
38
ACCEPTED MANUSCRIPT 4 59
patients who undergo SBTKAs are at an increased risk compared to unilateral TKA and to
60
further stratify the relevant variables and identify subgroups of patients that are at increased risk
61
of developing such complications.
63
RI PT
62 Materials and Methods
64 Study design
SC
65 66
This was a retrospective cohort study using data from the ACS-NSQIP database. The ACS-
68
NSQIP dataset includes over 135 variables collected on surgical patients from 696 centers across
69
the United States and worldwide, including Saudi Arabia, Canada,
70
Lebanon, United Kingdom, and the United Arab Emirates, and has information on 30-day
71
morbidity and mortality along with other various demographics. Specially trained personnel at
72
every collaborating institution collect de-identified medical information and log it into the
73
databank [17]. In accordance with our institutional guidelines, which follow the US Code of
74
Federal Regulations for the Protection of Human Subjects, Institutional Review Board approval
75
was not needed for our analysis because data were de-identified and collected as part of a quality
76
assurance activity.
78 79
TE D
EP
AC C
77
M AN U
67
Patient selection
80
Data from 2008 through 2015 were queried to identify patients who underwent unilateral TKA or
81
SBTKA performed under the same anesthesia using the current procedural terminology (CPT)
ACCEPTED MANUSCRIPT 5 code 27447. Patients who had other concurrent or concomitant procedures were excluded. Uni-
83
compartmental knee arthroplasty, CPT code 27446, was not included in the query. NSQIP
84
variables were used to exclude patients with disseminated cancer, those who underwent
85
emergency procedures or had an open wound and/or wound infection. ICD9 and ICD10 codes
86
were used to exclude patients who underwent total knee arthroplasty with arthropaties associated
87
with infection, osteomyelitis, malignant neoplasms and fractures.
88
Patient demographics, comorbidities, and selected laboratory values were obtained from the
89
ACS-NSQIP database as baseline characteristics (Table 1). These included age, gender, race,
90
American Society of Anesthesiology (ASA) classification, total operative time, functional status,
91
body mass index (BMI), tobacco use, diabetes mellitus, hypertension, steroid use, chronic
92
obstructive pulmonary disease (COPD), congestive heart failure (CHF), dyspnea, renal failure on
93
dialysis, anesthesia type, transfusion before surgery, bleeding disorders, prothrombin time (PTT),
94
international normalized ratio (INR), platelet count, white blood cell count, hematocrit (Hct), and
95
serum sodium levels. The BMI classification was adapted from the World Health organization
96
(WHO) global database[18]. Anemia was defined using the WHO sex based criteria[19].
97
Thirty-day mortality and morbidity, including cardiac, wound, respiratory, urinary tract, central
98
nervous system, sepsis, venous thromboembolism (VTE), bleeding, mortality, and return to the
99
operating room were recorded as adverse events. Venous thromboembolism was defines as deep
100
venous thrombosis and/or pulmonary embolism. Bleeding is defined in the NSQIP as red blood
101
cell (RBC) transfusion intraoperative / postoperative within the first 72 hours of surgery start
102
time. Variables with more than 20% missing data were removed from the analysis.
SC
M AN U
TE D
EP
AC C
103 104
RI PT
82
Statistical analysis
ACCEPTED MANUSCRIPT 6 105 Statistical analyses were done using Statistical Analysis System (SAS) software (version 9.1;
107
SAS Institute, Cary, North Carolina). Categorical variables were presented as number and
108
percentage, whereas continuous ones as mean and standard deviation. Continuous variables were
109
compared using the independent t-test and categorical variables using the Chi-square test. Odds
110
ratios (OR) for mortality and morbidities were calculated, using logistic regression with 95%
111
confidence intervals (CI). An initial univariate analysis was done to analyze the effect of SBTKA
112
on mortality and other postoperative complications (Table 2). Relevant confounders for specific
113
complications were controlled for (see Appendix 1) and a multivariate logistic regression
114
analysis was performed to detect the independent effect of the type of surgery, SBTKA or
115
unilateral TKA, on complications that were significant on initial analysis. Complications for
116
which SBTKA was found to be an independent risk factor were further analyzed by subgroup
117
stratification to identify specific subgroups of patients that might be at an even higher risk for
118
that specific complication. The level of significance for p-value was < 0.05.
119
121
Results
EP
120
TE D
M AN U
SC
RI PT
106
A total of 155,022 patients were identified, of which 150,581 underwent unilateral TKA (97.1%)
123
and 4,441 underwent SBTKA (2.9%). Table 1 shows the baseline characteristics of each group.
124
There were several statically significant differences between the baseline characteristics of the
125
two groups. Patients who underwent SBTKA were more likely to be younger than 65 years old
126
(50.98% versus 40.38% P < 0.0001), male (42.35% versus 37.42% P < 0.0001), have a lower
127
ASA classification (59.88% versus 52.08% P < 0.0001), have a longer mean operative time (149
AC C
122
ACCEPTED MANUSCRIPT 7 minutes ± 54.70 versus 92 minutes ± 36.39 P < 0.0001), undergo general anesthesia more
129
frequently (61.76% versus 50.34% P < 0.0001), have a higher preoperative Hct (41.03% ± 4.13
130
versus 40.72% ± 4.06 P < 0.0001), and lower mean serum creatinine (mg/dL) levels (0.88
131
mg/dL ± 0.32 versus 0.92 mg/dL ± 0.41 P < 0.0001). SBTKA patients were less likely to have
132
diabetes on oral medications or insulin (15.02% versus 18.05% P < 0.0001), hypertension on
133
medications (61.18% versus 66.08% P < 0.0001), severe chronic obstructive pulmonary disease
134
(COPD) (2.3% versus 3.59% P < 0.0001), congestive heart failure (CHF) (0.09% versus 0.26%
135
P = 0.0297), dyspnea (4.5% versus 6.39% P < 0.0001) or an international normalized ratio
136
(INR) of more than 1.2 (2.01% versus 3.08% P = 0.0008).
137
Regarding the 30-day outcomes, the SBTKA group was at a higher risk for developing VTE (OR
138
1.97, 95% CI: 1.64-2.37), bleeding (OR 3.95, 95% CI: 3.65-4.27), composite morbidity (OR
139
1.48, 95% CI: 1.30-1.67), progressive renal insufficiency (OR 2.71, 95% CI: 1.50-4.88) and
140
urinary tract infection (OR 1.70, 95% CI: 1.31-2.20). Multivariate logistic regression analysis
141
showed no statistically significant differences between the two groups in terms of mortality,
142
cardiac complications (myocardial infarction and cardiac arrest necessitating CPR), pneumonia,
143
prolonged or unplanned intubations, acute renal failure, cerebrovascular accidents or wound
144
complications, whether superficial or deep. There was also no difference in return to the
145
operating room between the two groups after adjusting for confounders (Table 2).
146
Upon stratification of different baseline characteristics in patients who had a VTE, several
147
subgroups were at a risk higher than the baseline adjusted odds ratio of 1.97 (95% CI: 1.64-2.37)
148
when undergoing SBTKA compared to unilateral TKA. These included patients who are black
149
(OR 3.10, 95% CI: 1.85- 5.22, P < 0.0001), Asian (OR 3.48, 95% CI: 1.35- 8.98, P = 0.0099),
150
have a BMI between 30 and 34.9 Kg/m2 (OR 2.75, 95% CI: 1.96- 3.85, P < 0.0001), are diabetic
AC C
EP
TE D
M AN U
SC
RI PT
128
ACCEPTED MANUSCRIPT 8 (OR 2.01, 95% CI: 1.25- 3.25, P = 0.0043), or underwent anesthesia other than general or spinal
152
/ epidural (OR 3.70, 95% CI: 2.20- 6.19, P < 0.0001). Patients without a bleeding disorder were
153
particularly at an increased risk for VTE (OR 2.01, 95% CI: 1.66- 2.42, P < 0.0001). Operative
154
time of more than 120 minutes did not confer any increased risk for VTE compared to operative
155
times of less than 120 minutes. Patient subgroups that showed an increased risk of VTE when
156
undergoing SBTKA without reaching statistical significance include patients older than 85 years,
157
those with partial functional dependence. This might be due to the limited occurrence of these
158
variables in the SBTKA group (Table 3).
SC
RI PT
151
Subgroups of patients undergoing SBTKA who were at a higher risk for bleeding than the
160
baseline adjusted odds ratio of 3.95 (95% CI: 3.65-4.27) compared to the unilateral TKA
161
counterparts included patients older than 85 years (OR 5.64, 95% CI: 2.59- 12.29, P < 0.0001),
162
those who are black, Asian or of origins other than white, black or Asian, those with BMI <18.5
163
or >30 Kg/m2, patients who underwent general anesthesia or anesthesia other than spinal /
164
epidural. Patients with operative times < 120 minutes and those with no preoperative anemia
165
were also at a higher risk for bleeding. Patients with an INR >1.2 preoperatively had a risk for
166
bleeding (OR 2.51, 95% CI: 1.29- 4.87, P = 0.0067) lower than those with an INR ≤ 1.2 (OR
167
3.98, 95% CI: 3.68- 4.31, P < 0.0001). Similar findings of lower risks of bleeding were found in
168
patients who underwent spinal/epidural anesthesia (OR 2.71, 95% CI: 2.31- 3.19, P < 0.0001)
169
compared to other types of anesthesia, or had an operative time of more than 180 minutes (OR
170
2.89, 95% CI: 2.42- 3.45, P < 0.0001) (Table 4).
172
TE D
EP
AC C
171
M AN U
159
Discussion
ACCEPTED MANUSCRIPT 9 The aim of our study was to evaluate whether SBTKA was a risk factor for various
174
complications within the 30 postoperative days compared to unilateral TKA and to analyze
175
whether there are specific subgroups of patients that are at higher risk for certain complications.
176
SBTKA was found to be a risk factor for thromboembolism, bleeding, urinary tract infection,
177
progressive renal insufficiency and composite morbidity. After adjusting for baseline
178
characteristics the SBTKA group had twice the risk of VTE and almost four times the risk of
179
bleeding compared to the unilateral TKA group. The increased risk persisted across most of the
180
stratification analysis, and none of the subgroups was protected from VTE or bleeding when
181
undergoing SBTKA versus unilateral TKA. Although none of the variables was protective
182
against VTE or bleeding, certain characteristics conferred a higher increase in the risks of VTE
183
and bleeding, while others carried a slightly lower risk for these complications (Tables 3 and 4).
184
In our study SBTKA was not associated with an increased risk of mortality [unadjusted OR 1.23
185
(0.55-2.79) P = 0.4956], return to operating room [OR 1.18 (0.92-1.51) P = 0.1929], cardiac
186
complications or wound infections compared to unilateral TKA.
TE D
M AN U
SC
RI PT
173
Although the majority of patients with knee osteoarthritis suffer from bilateral disease
188
[20], less than 3% of patients in the ACS-NSQIP database underwent a bilateral procedure,
189
which is commensurate with numbers found in the literature [5, 7]. This is understandable given
190
the amount of recent literature that has found an increase in morbidity and mortality in those
191
undergoing a SBTKA [3, 4, 21]. However, there are data, which suggest that, after matching for
192
baseline characteristics, SBTKA may be associated with lower costs and better outcomes,
193
including prosthesis survival, lower infection rates and no difference in perioperative
194
complications.[5, 6, 22-25]. Additionally, patient reported outcomes favor performing a SBTKA
195
versus a staged procedure [26]. The statement from the consensus conference on SBTKA
AC C
EP
187
ACCEPTED MANUSCRIPT 10 196
showed that 81% of participants agreed that this procedure is associated with an increased risk of
197
perioperative complications in unselected patients. They suggested that hospitals should have
198
stricter criteria to exclude patients with increased cardiac risk factors [27]. Several studies have tried to identify risk factors associated with mortality and morbidity
200
in SBTKA in attempts to establish patient selection criteria. These risk factors include old age[4,
201
28-33], male sex[4, 28, 29], preoperative cardiac disease[28, 34-37] and pulmonary
202
comorbidities[33].
SC
RI PT
199
Two recent studies from the ACS-NSQIP database have matched patients in each of the
204
SBTKA and unilateral TKA groups to prevent selection bias [10, 11]. They have found that
205
those who underwent a SBTKA had an increased risk for postoperative major medical
206
complications as well as return to the operating room, but no differences in infection rates,
207
readmission rates, or mortality. However, they have failed to perform a multivariate analysis to
208
confirm that SBTKA is an independent risk factor for return to the operating room. Our analysis
209
showed similar results, although the increased risk for return to the operating room did not
210
persist after adjusting for confounders. We also found an increased risk for VTE and bleeding,
211
which were not specifically studied or stratified in these studies. These findings are in
212
contradistinction to previous studies that have suggested an increased risk of mortality in patients
213
undergoing a SBTKA [3, 4, 21, 38]. Other studies have reported increased rates of myocardial
214
infarction, postoperative confusion, and the need for intensive monitoring after SBTKA
215
compared to unilateral TKA, however, with similar 30 day and one year mortality rates and
216
similar risks of pulmonary embolism, infection, and deep venous thrombosis for the two
217
groups.[30]
AC C
EP
TE D
M AN U
203
ACCEPTED MANUSCRIPT 11 A cohort analysis from the Canadian Hospital Morbidity Database showed higher rates of
219
transfusion in patients who underwent SBTKA (41%) as compared to a unilateral TKA (13.3%)
220
or the second knee in a staged procedure (18.6%) [2]. This could correspond to the increased risk
221
of postoperative bleeding in patients undergoing SBTKA in the present study, and the results
222
from a previous ACS-NSQIP study [10]. Although the ACS-NSQIP does not provide
223
information regarding the use of drains, two recent studies have shown that there are no
224
differences in postoperative bleeding or clinical outcomes, with or without the use of a drain [39,
225
40]. A recent meta-analysis on the use of tranexamic acid in patients undergoing SBTKA
226
showed favorable outcomes with regards to postoperative hemoglobin, drainage volume,
227
transfusion rate, and number of units transfused, without any increased risk of VTE[41].
228
Therefore, the increased risk of bleeding may be decreased with the use of tranexamic acid in
229
patients undergoing SBTKA. Data regarding the use of tranexamic acid was not included in the
230
ACS-NSQIP.
TE D
M AN U
SC
RI PT
218
In the study by Hart et al. the unadjusted rate of pulmonary embolism was higher in
232
SBTKA (1.4%) versus unilateral TKA (0.7%) [10]. Two previous large studies have shown
233
similar findings, as well as ORs similar to those of the present study during the first three months
234
postoperatively [42, 43]. Although there are data to suggest that this increased risk is similar,
235
whether patients undergo simultaneous or staged procedures[2, 44], other studies have found that
236
simultaneous procedures have an increased risk of VTE as compared to staged procedures [3,
237
43]. As with our study, Bohm et al. found that male sex, age more than 75 years, and at least one
238
comorbidity, were at increased risk of pulmonary embolism [2]. Furthermore, there is no
239
consensus on the length of time between the first and second surgeries of a staged bilateral TKA.
240
While one study found staggered bilateral total knee replacement, performed four to seven days
AC C
EP
231
ACCEPTED MANUSCRIPT 12 241
apart in a single hospitalization, to have significantly lower rate of complications compared to
242
SBTKA[45], another study found procedures separated by the same period of time to have
243
similar complication profiles compared to SBTKA.[46] A significant finding in our study was the lower risk of bleeding and VTE in the
245
subgroup of patients undergoing SBTKA under spinal / epidural anesthesia compared to general
246
or other forms of anesthesia. SBTKA was an independent risk factor for bleeding OR 3.95 (95%
247
CI: 3.65-4.27, P <0.0001), however in the subgroup of spinal / epidural anesthesia the risk was
248
2.71 (95% CI: 2.31-3.19, P < 0.0001). Similar results of lower percentage of SBTKA patients
249
requiring transfusion under neuraxial anesthesia was reported by Stundner et al in a national
250
database analysis [47]. However the same study did not find any decreased risk of pulmonary
251
embolism using neuraxial anesthesia for SBTKA patients. Our study is the first to demonstrate
252
that the risk of thromboembolism in the subgroup of patients undergoing SBTKA under spinal /
253
epidural anesthesia is lower compared to those undergoing the same procedure under general
254
anesthesia. Whereas SBTKA had a twofold risk of thromboembolism compared to unilateral
255
TKA (OR 1.97, 95% CI: 1.64-2.37, P <0.0001), in the subgroup of patients undergoing spinal /
256
epidural anesthesia SBTKA was still a risk factor for thromboembolism however to a lesser
257
degree (OR 1.73, 95% CI: 1.21-2.49, P = 0.003).
SC
M AN U
TE D
EP
Other significant findings after subgroup stratification in the current study include the
AC C
258
RI PT
244
259
increased risk of VTE in patients of black or Asian origin undergoing SBTKA. Although
260
SBTKA was found to be an independent risk factor for this complication (OR 1.97, 95% CI:
261
1.64-2.37, P < 0.0001), patients of black and Asian race were at a much higher risk of VTE with
262
OR of 3.10 (95% CI: 1.85- 5.22,) and 3.48 (95% CI: 1.35- 8.98), respectively, when undergoing
263
SBTKA rather than a unilateral procedure. This finding highlights the importance of race to be
ACCEPTED MANUSCRIPT 13 considered when counseling patients for SBTKA. In a population study in California, SooHoo et
265
al. have shown that black race is associated with a 73% increased rate of pulmonary embolism in
266
patients undergoing total knee arthroplasty compared to white counterparts. The increased risk of
267
VTE in black race and decreased risk in Asians is reported in several studies [48, 49]. This is in
268
contrast to the findings in our study where the subgroup of patients of Asian origin had an
269
increased risk of VTE when undergoing SBTKA.
RI PT
264
Although a recent NSQIP study has shown that an increase in surgical duration to be
271
directly associated with an increase in the risk of VTE [50], increase in operative time did not
272
increase the risk of VTE in SBTKA patients compared to their unilateral TKA counterparts. In
273
contrast the subgroup of patients with an operative time < 120 minutes had the higher risk of
274
VTE. While this finding was statistically significant, it should not be assumed that SBTKAs with
275
longer operative times are protective against VTE. This might be due to more rigorous VTE
276
prophylaxis measures undertaken for patients who had longer operative times.
TE D
M AN U
SC
270
Several previous studies have tried to analyze predictors or risk factors of transfusion in
278
total hip and knee arthroplasty with varying results. While some have found no correlation
279
between obesity and blood loss[51-53], others have found increased blood loss with elevated
280
BMI[54]. Although SBTKA is associated with increased blood loss compared to unilateral
281
procedures, our study showed that in the subgroup of patients with BMI > 30 Kg/m2, SBTKA
282
was associated with even a higher rate of bleeding. Black race, Asian origin and race other than
283
white, black or Asian were also subgroups that showed increased likelihood of bleeding when
284
undergoing SBTKA compared to a unilateral procedure. It has been shown that increased age is
285
associated with increased blood loss and transfusion in patients undergoing TKA [53, 55] or
286
THA [56, 57]. However the effect of age and bilaterality of the procedure on bleeding has not
AC C
EP
277
ACCEPTED MANUSCRIPT 14 been analyzed. Although SBTKA was associated with a significantly higher rate of bleeding
288
across all age groups compared to unilateral procedures, patients older than 85 years were at a
289
particularly increased risk of this complication when undergoing SBTKA compared to unilateral
290
TKA (OR 5.64 95% CI: 2.59 - 12.29). To deter its effect on the outcome, preoperative Hct was
291
one of the confounders controlled for in the subgroup analysis. These subgroups of patents with
292
increased risk of complications should be noted when deciding between unilateral or bilateral
293
TKA.
SC
RI PT
287
There were several unusual findings in the subgroup stratification that could not be
295
explained, although they were statistically significant after adjusting for confounders. Patients
296
with bleeding disorders and INR > 1.2 were at a lower risk of bleeding when undergoing
297
SBTKA compared to patients with no bleeding disorders and an INR ≤ 1.2. This might be due to
298
more rigorous homeostasis in these subgroups or the use of Tranexamic acid which the NSQIP
299
does not record.
300
An important limitation of this study is that the ACS-NSQIP is unable to capture staged
301
procedures or the time between them and does not include outcomes beyond 30 days. Some
302
cases of unilateral TKA in this study may have been part of a staged procedure, thus skewing the
303
results. Other limitations involving shortfalls of the database include an inability to gather data
304
on surgeon experience, hospital volume, VTE prophylaxis, use of drains, re-infusion systems,
305
tourniquet, and tranexamic acid. It is also not known whether VTE events were symptomatic or
306
diagnosed on routine ultrasounds. Functional outcomes and cost are also not recorded.
307
Furthermore, by using the NSQIP database or any other population based database selection bias
308
cannot be eliminated. This is depicted by the patient demographics (Table 1), that shows patients
309
undergoing SBTKA are healthier with less morbidities.
AC C
EP
TE D
M AN U
294
ACCEPTED MANUSCRIPT 15 310 Conclusion
312
SBTKA confers an increased risk of postoperative VTE and bleeding at 30 days, as well as an
313
increased risk of composite morbidity with no increase in mortality. Particular patient
314
characteristics may confer an increased risk for these complications. As the debate regarding the
315
risks and benefits of performing a SBTKA versus a unilateral or staged bilateral TKA continues,
316
research must focus on identifying individual patient risk factors for various complications, as
317
well as tailoring specific intraoperative practices to reduce the risk.
SC
RI PT
311
319
M AN U
318 References
320
EP
TE D
1. Lindberg-Larsen M, Jorgensen CC, Husted H, Kehlet H. Early morbidity after simultaneous and staged bilateral total knee arthroplasty. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 23(3): 831, 2015 2. Bohm ER, Molodianovitsh K, Dragan A, Zhu N, Webster G, Masri B, Schemitsch E, Dunbar M. Outcomes of unilateral and bilateral total knee arthroplasty in 238,373 patients. Acta orthopaedica 87 Suppl 1: 24, 2016 3. Bolognesi MP, Watters TS, Attarian DE, Wellman SS, Setoguchi S. Simultaneous vs staged bilateral total knee arthroplasty among Medicare beneficiaries, 2000-2009. The Journal of arthroplasty 28(8 Suppl): 87, 2013 4. Odum SM, Springer BD. In-Hospital Complication Rates and Associated Factors After Simultaneous Bilateral Versus Unilateral Total Knee Arthroplasty. The Journal of bone and joint surgery American volume 96(13): 1058, 2014 5. Odum SM, Troyer JL, Kelly MP, Dedini RD, Bozic KJ. A cost-utility analysis comparing the cost-effectiveness of simultaneous and staged bilateral total knee arthroplasty. The Journal of bone and joint surgery American volume 95(16): 1441, 2013 6. Lin AC, Chao E, Yang CM, Wen HC, Ma HL, Lu TC. Costs of staged versus simultaneous bilateral total knee arthroplasty: a population-based study of the Taiwanese National Health Insurance Database. Journal of orthopaedic surgery and research 9: 59, 2014 7. Fu D, Li G, Chen K, Zeng H, Zhang X, Cai Z. Comparison of clinical outcome between simultaneous-bilateral and staged-bilateral total knee arthroplasty: a systematic review of retrospective studies. The Journal of arthroplasty 28(7): 1141, 2013 8. Oakes DA, Hanssen AD. Bilateral total knee replacement using the same anesthetic is not justified by assessment of the risks. Clinical orthopaedics and related research (428): 87, 2004
AC C
321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343
ACCEPTED MANUSCRIPT 16
EP
TE D
M AN U
SC
RI PT
9. Restrepo C, Parvizi J, Dietrich T, Einhorn TA. Safety of simultaneous bilateral total knee arthroplasty. A meta-analysis. The Journal of bone and joint surgery American volume 89(6): 1220, 2007 10. Hart A, Antoniou J, Brin YS, Huk OL, Zukor DJ, Bergeron SG. Simultaneous Bilateral Versus Unilateral Total Knee Arthroplasty: A Comparison of 30-Day Readmission Rates and Major Complications. The Journal of arthroplasty 31(1): 31, 2016 11. Suleiman LI, Edelstein AI, Thompson RM, Alvi HM, Kwasny MJ, Manning DW. Perioperative Outcomes Following Unilateral Versus Bilateral Total Knee Arthroplasty. The Journal of arthroplasty 30(11): 1927, 2015 12. Soudry M, Binazzi R, Insall JN, Nordstrom TJ, Pellicci PM, Goulet JA. Successive bilateral total knee replacement. The Journal of bone and joint surgery American volume 67(4): 573, 1985 13. Ritter MA, Meding JB. Bilateral simultaneous total knee arthroplasty. The Journal of arthroplasty 2(3): 185, 1987 14. Morrey BF, Adams RA, Ilstrup DM, Bryan RS. Complications and mortality associated with bilateral or unilateral total knee arthroplasty. The Journal of bone and joint surgery American volume 69(4): 484, 1987 15. Kim YH, Choi YW, Kim JS. Simultaneous bilateral sequential total knee replacement is as safe as unilateral total knee replacement. The Journal of bone and joint surgery British volume 91(1): 64, 2009 16. Hall BL, Hamilton BH, Richards K, Bilimoria KY, Cohen ME, Ko CY. Does surgical quality improve in the American College of Surgeons National Surgical Quality Improvement Program: an evaluation of all participating hospitals. Ann Surg 250(3): 363, 2009 17. Surgeons ACo. American College of Surgeons National Surgical Quality Improvement Program. User guide for the 2015 participant use data file. In. 2015 18. WHO Global Database on Body Mass Index (BMI): an interactive surveillance tool for monitoring nutrition transition. Public Health Nutrition 9(5): 658, 2006 19. Organization WH. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. In: Vitamin and Mineral Nutrition Information System (VMNIS). Geneva. 2011 20. Shao Y, Zhang C, Charron KD, Macdonald SJ, McCalden RW, Bourne RB. The fate of the remaining knee(s) or hip(s) in osteoarthritic patients undergoing a primary TKA or THA. The Journal of arthroplasty 28(10): 1842, 2013 21. Memtsoudis SG, Ma Y, Gonzalez Della Valle A, Mazumdar M, Gaber-Baylis LK, MacKenzie CR, Sculco TP. Perioperative outcomes after unilateral and bilateral total knee arthroplasty. Anesthesiology 111(6): 1206, 2009 22. Reuben JD, Meyers SJ, Cox DD, Elliott M, Watson M, Shim SD. Cost comparison between bilateral simultaneous, staged, and unilateral total joint arthroplasty. The Journal of arthroplasty 13(2): 172, 1998 23. Poultsides LA, Memtsoudis SG, Vasilakakos T, Wanivenhaus F, Do HT, Finerty E, Alexiades M, Sculco TP. Infection following simultaneous bilateral total knee arthroplasty. The Journal of arthroplasty 28(8 Suppl): 92, 2013 24. Courtney PM, Melnic CM, Alosh H, Shah RP, Nelson CL, Israelite CL. Is bilateral total knee arthroplasty staged at a one-week interval safe? A matched case control study. The Journal of arthroplasty 29(10): 1946, 2014 25. Meehan JP, Danielsen B, Tancredi DJ, Kim S, Jamali AA, White RH. A population-based comparison of the incidence of adverse outcomes after simultaneous-bilateral and staged-
AC C
344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388
ACCEPTED MANUSCRIPT 17
EP
TE D
M AN U
SC
RI PT
bilateral total knee arthroplasty. The Journal of bone and joint surgery American volume 93(23): 2203, 2011 26. Abram SG, Nicol F, Spencer SJ. Patient reported outcomes in three hundred and twenty eight bilateral total knee replacement cases (simultaneous versus staged arthroplasty) using the Oxford Knee Score. International orthopaedics 40(10): 2055, 2016 27. Memtsoudis SG, Hargett M, Russell LA, Parvizi J, Cats-Baril WL, Stundner O, Sculco TP, Consensus Conference on Bilateral Total Knee Arthroplasty G. Consensus statement from the consensus conference on bilateral total knee arthroplasty group. Clinical orthopaedics and related research 471(8): 2649, 2013 28. Memtsoudis SG, Ma Y, Chiu YL, Poultsides L, Gonzalez Della Valle A, Mazumdar M. Bilateral total knee arthroplasty: risk factors for major morbidity and mortality. Anesth Analg 113(4): 784, 2011 29. Ritter MA, Harty LD, Davis KE, Meding JB, Berend M. Simultaneous bilateral, staged bilateral, and unilateral total knee arthroplasty. A survival analysis. The Journal of bone and joint surgery American volume 85-A(8): 1532, 2003 30. Bullock DP, Sporer SM, Shirreffs TG, Jr. Comparison of simultaneous bilateral with unilateral total knee arthroplasty in terms of perioperative complications. The Journal of bone and joint surgery American volume 85-A(10): 1981, 2003 31. Mangaleshkar SR, Prasad PS, Chugh S, Thomas AP. Staged bilateral total knee replacement-a safer approach in older patients. The Knee 8(3): 207, 2001 32. Ritter MA, Harty LD. Debate: simultaneous bilateral knee replacements: the outcomes justify its use. Clinical orthopaedics and related research (428): 84, 2004 33. Fabi DW, Mohan V, Goldstein WM, Dunn JH, Murphy BP. Unilateral vs bilateral total knee arthroplasty risk factors increasing morbidity. The Journal of arthroplasty 26(5): 668, 2011 34. Peskun C, Mayne I, Malempati H, Kosashvili Y, Gross A, Backstein D. Cardiovascular disease predicts complications following bilateral total knee arthroplasty under a single anesthetic. The Knee 19(5): 580, 2012 35. Parvizi J, Sullivan TA, Trousdale RT, Lewallen DG. Thirty-day mortality after total knee arthroplasty. The Journal of bone and joint surgery American volume 83-A(8): 1157, 2001 36. Leonard L, Williamson DM, Ivory JP, Jennison C. An evaluation of the safety and efficacy of simultaneous bilateral total knee arthroplasty. The Journal of arthroplasty 18(8): 972, 2003 37. Lane GJ, Hozack WJ, Shah S, Rothman RH, Booth RE, Jr., Eng K, Smith P. Simultaneous bilateral versus unilateral total knee arthroplasty. Outcomes analysis. Clinical orthopaedics and related research (345): 106, 1997 38. Hussain N, Chien T, Hussain F, Bookwala A, Simunovic N, Shetty V, Bhandari M. Simultaneous versus staged bilateral total knee arthroplasty: a meta-analysis evaluating mortality, peri-operative complications and infection rates. HSS journal : the musculoskeletal journal of Hospital for Special Surgery 9(1): 50, 2013 39. Jhurani A, Shetty GM, Gupta V, Saxena P, Singh N. Effect of Closed Suction Drain on Blood Loss and Transfusion Rates in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Study. Knee surgery & related research 28(3): 201, 2016 40. Watanabe T, Muneta T, Yagishita K, Hara K, Koga H, Sekiya I. Closed Suction Drainage Is Not Necessary for Total Knee Arthroplasty: A Prospective Study on Simultaneous Bilateral Surgeries of a Mean Follow-Up of 5.5 Years. The Journal of arthroplasty 31(3): 641, 2016
AC C
389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432
ACCEPTED MANUSCRIPT 18
EP
TE D
M AN U
SC
RI PT
41. Jiang X, Ma XL, Ma JX. Efficiency and Safety of Intravenous Tranexamic Acid in Simultaneous Bilateral Total Knee Arthroplasty: A Systematic Review and Meta-analysis. Orthopaedic surgery 8(3): 285, 2016 42. Barrett J, Baron JA, Losina E, Wright J, Mahomed NN, Katz JN. Bilateral total knee replacement: staging and pulmonary embolism. The Journal of bone and joint surgery American volume 88(10): 2146, 2006 43. Memtsoudis SG, Besculides MC, Reid S, Gaber-Baylis LK, Gonzalez Della Valle A. Trends in bilateral total knee arthroplasties: 153,259 discharges between 1990 and 2004. Clinical orthopaedics and related research 467(6): 1568, 2009 44. Sheth DS, Cafri G, Paxton EW, Namba RS. Bilateral Simultaneous vs Staged Total Knee Arthroplasty: A Comparison of Complications and Mortality. The Journal of arthroplasty 31(9 Suppl): 212, 2016 45. Sliva CD, Callaghan JJ, Goetz DD, Taylor SG. Staggered bilateral total knee arthroplasty performed four to seven days apart during a single hospitalization. The Journal of bone and joint surgery American volume 87(3): 508, 2005 46. Liu J, Elkassabany N, Poultsides L, Nelson CL, Memtsoudis SG. Staging Bilateral Total Knee Arthroplasty During the Same Hospitalization: The Impact of Timing. The Journal of arthroplasty 30(7): 1172, 2015 47. Stundner O, Chiu YL, Sun X, Mazumdar M, Fleischut P, Poultsides L, Gerner P, Fritsch G, Memtsoudis SG. Comparative perioperative outcomes associated with neuraxial versus general anesthesia for simultaneous bilateral total knee arthroplasty. Regional anesthesia and pain medicine 37(6): 638, 2012 48. Heit JA, Beckman MG, Bockenstedt PL, Grant AM, Key NS, Kulkarni R, Manco-Johnson MJ, Moll S, Ortel TL, Philipp CS. Comparison of characteristics from White- and BlackAmericans with venous thromboembolism: a cross-sectional study. Am J Hematol 85(7): 467, 2010 49. White RH, Keenan CR. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res 123 Suppl 4: S11, 2009 50. Kim JY, Khavanin N, Rambachan A, McCarthy RJ, Mlodinow AS, De Oliveria GS, Jr., Stock MC, Gust MJ, Mahvi DM. Surgical duration and risk of venous thromboembolism. JAMA Surg 150(2): 110, 2015 51. Hrnack SA, Skeen N, Xu T, Rosenstein AD. Correlation of body mass index and blood loss during total knee and total hip arthroplasty. Am J Orthop (Belle Mead NJ) 41(10): 467, 2012 52. Park JH, Rasouli MR, Mortazavi SM, Tokarski AT, Maltenfort MG, Parvizi J. Predictors of perioperative blood loss in total joint arthroplasty. The Journal of bone and joint surgery American volume 95(19): 1777, 2013 53. Bong MR, Patel V, Chang E, Issack PS, Hebert R, Di Cesare PE. Risks associated with blood transfusion after total knee arthroplasty. The Journal of arthroplasty 19(3): 281, 2004 54. Frisch N, Wessell NM, Charters M, Peterson E, Cann B, Greenstein A, Silverton CD. Effect of Body Mass Index on Blood Transfusion in Total Hip and Knee Arthroplasty. Orthopedics 39(5): e844, 2016 55. Guerin S, Collins C, Kapoor H, McClean I, Collins D. Blood transfusion requirement prediction in patients undergoing primary total hip and knee arthroplasty. Transfus Med 17(1): 37, 2007
AC C
433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476
ACCEPTED MANUSCRIPT 19 56. Browne JA, Adib F, Brown TE, Novicoff WM. Transfusion rates are increasing following total hip arthroplasty: risk factors and outcomes. The Journal of arthroplasty 28(8 Suppl): 34, 2013 57. Walsh M, Preston C, Bong M, Patel V, Di Cesare PE. Relative risk factors for requirement of blood transfusion after total hip arthroplasty. The Journal of arthroplasty 22(8): 1162, 2007
RI PT
477 478 479 480 481 482
AC C
EP
TE D
M AN U
SC
483
ACCEPTED MANUSCRIPT
Appendix 1. Confounders Return OR
Composite Morbidity
Intubation [Unplanned Intubation + Intubation >48]
X X
X X X X X X X X X X
X X
X X X X X X X X X X X X X X X
X X
X X X X X X
X X
X X X
X X X X X X X X X X X
X X X X X X X X
X X X
X X
X X X
X X
X X X X X X X X X X X X X X X
X
Wound Complications
Deep Infection
Sepsis
X X
X X
X X
X X
X
X X X X X X
X X X X X X X
X X X X X X X
X X X X X X X
X X X X
X X X X
X X X X
X X X X
X X
X X
X X
X X X X X X X X X
X X X X X X X X X
X X X X X X X X X
X
X
X
X
X
X X X X X X X
X X X
X X
X
X
X X
Progressive Renal Insuffieciency
X X
SC
X X X X X X X X
M AN U
X X X
TE D
X X X
X X X X X X X
EP
X X X
UTI
RI PT
Thromboe mbolism
AC C
Age Gender Race Type of Anesthesia ASA Class Mean Total Operation Time min Days from admission to operation Transfusions in 72 h before surgery CHF w/in 30days Tobacco use in past year History of severe COPD Acute renal failure Currently on dialysis Bleeding disorder Weight loss > 10% in previous 6 months BMI Diabetic on oral drugs or insulin Hypertension requiring meds Steroid use for chronic condition WBC count Platelet count INR BUN Creatinine Serum albumin Dyspnea Functional health status Prior to Surgery Ascites Hematocrit PTT
Bleeding
X X
X X X
X X X X
X
ACCEPTED MANUSCRIPT
58,188 (37.6%) 96,724 (62.4%)
56310 (37.42%) 94168 (62.58%)
121582 (88.3%) 11,330 (8.2%) 3,368 (2.4%) 1,338 (1%)
117858 (88.34%) 11027 (8.27%) 3229 (2.42%) 1301 (0.98%)
151563 (98.4%) 2,421 (1.6%) 88 (0.1%) 32.00 ± 7.05 377 (0.2%) 15,288 (9.9%) 42,246 (27.3%) 43,943 (28.4%) 29,191 (18.9%) 23,513 (15.2%) 13,198 (8.5%) 27,854 (18%) 102220 (65.9%) 5,261 (3.4%)
p-value <0.0001 <0.0001
<0.0001
3724 (88.6%) 303 (7.21%) 139 (3.31%) 37 (0.88%)
0.0003
78345 (52.08%) 72099 (47.92%) 92.38 ± 36.39 125476 (83.33%) 21969 (14.59%) 3125 (2.08%)
2654 (59.88%) 1778 (40.12%) 148.97 ± 54.70 1449 (32.63%) 1943 (43.75%) 1049 (23.62%)
<0.0001
147206 (98.35%) 2377 (1.59%) 87 (0.06%) 32.99 ± 7.05 364 (0.24%) 14902 (9.93%) 41041 (27.34%) 42665 (28.42%) 28290 (18.84%) 22868 (15.23%) 12844 (8.53%) 27187 (18.05%) 99503 (66.08%) 5124 (3.4%)
4357 (98.98%) 44 (1%) 1 (0.02%) 33.13 ± 7.07 13 (0.29%) 386 (8.72%) 1205 (27.21%) 1278 (28.86%) 901 (20.35%) 645 (14.57%) 354 (7.97%) 667 (15.02%) 2717 (61.18%) 137 (3.08%)
0.0052
M AN U
SC
1878 (42.35%) 2556 (57.65%)
TE D
80,999 (52.3%) 73,877 (47.7%) 94.00 ± 38.22 126925 (81.9%) 23,912 (15.4%) 4,174 (2.7%)
Bilateral TKA n=4,441 (2.86%) 64.09 ± 8.81 2264 (50.98%) 2149 (48.39%) 28 (0.63%)
RI PT
Unilateral TKA n=150581 (97.14%) 66.79 ± 9.76 60,806 (40.38%) 86589 (57.5%) 3186 (2.12%)
EP
Age (years) <65 65-85 >85 Gender Male Female Race / Ethnicity White Black Asian Other ASA Class I - II III - V Mean Total Operation Time(min) <120 min 120-179 min ≥180 min Functional status prior to surgery Independent Partially dependent Dependent BMI (Kg/m2)a <18.5 18.5-24.9 25-29.9 30-34.9 35-39.9 ≥40 Smoker Diabetes on oral drugs or insulin Hypertension requiring medication Steroid use for chronic condition
All TKAs (n=155022) 66.71 ± 9.74 63,070 (40.7%) 88,738 (57.2%) 3,214 (2.1%)
AC C
Table 1. Patient Characteristics
<0.0001 <0.0001
0.2075 0.02
0.1888 <0.0001 <0.0001 0.2488
ACCEPTED MANUSCRIPT
102 (2.3%) 200 (4.5%) 4 (0.09%)
<0.0001 <0.0001 0.0297
2742 (61.76%) 1311 (29.53%) 387 (8.72%) 0 (0%) 5 (0.11%) 0.88 ± 0.32 3764 (89.83%) 426 (10.17%) 6 (0.14%) 84 (1.89%) 4 (0.09%) 6.94 ± 1.96 4066 (96.56%) 145 (3.44%) 246.79 ± 66.22 169 (4.02%) 4036 (95.98%) 1.01 ± 0.24 2878 (97.99%) 59 (2.01%) 139.61 ± 2.71 256 (6.18%) 3884 (93.82%) 41.03 ± 4.13 3628 (85.85%) 575 (13.61%) 23 (0.54%) 29.06 ± 4.67
<0.0001
AC C
EP
TE D
M AN U
SC
RI PT
Severe COPD 5,510 (3.6%) 5408 (3.59%) Dyspnea 9,827 (6.3%) 9627 (6.39%) CHF (within 30 days) 389 (0.3%) 385 (0.26%) Anesthesia technique General 78,528 (50.7%) 75786 (50.34%) Spinal/Epidural 62,053 (40%) 60742 40.34%) Others 14,418 (9.3%) 14031 (9.32%) Acute renal failure 46 (0.00%) 46 (0.03%) Currently on dialysis 234 (0.2%) 229 (0.15%) Pre-operative serum creatinine (mg/dL) 0.92 ± 0.41 0.92 ± 0.41 <1.2 (mg/dL) 127435 (87.7%) 123671 (87.76%) ≥1.2 (mg/dL) 17,681 (12.2%) 17255 (12.24%) >10% loss body weight in last 6 months 205 (0.1%) 199 (0.13%) Bleeding disorders 3,717 (2.4%) 3633 (2.41%) Transfusion PRBCs in 72 hours before surgery 71 (0.00%) 67 (0.04%) Pre-operative WBC (103 cells/µL) 7.05 ± 2.17 7.06 ± 2.17 ≤11 (103 cells/µL) 141444 (96.4%) 137378 (96.37%) 3 >11 (10 cells/µL) 5,320 (3.6%) 5175 (3.63%) Pre-operative platelet count (per µL) 244.42 ± 66.65 244.34 ± 66.66 ≤150 (per µL) 7,222 (4.9%) 7053 (4.95%) >150 (per µL) 139514 (95.1%) 135478 (95.05%) Pre-operative INR 1.03 ± 0.26 1.03 ± 0.26 ≤1.2 99,362 (96.9%) 96484 (96.92%) >1.2 3,129 (3.1%) 3070 (3.08%) Pre-operative serum sodium (mEq/L) 139.48 ± 2.78 139.47 ± 2.78 ≤135 (mEq/L) 10,267 (7.1%) 10011 (7.18%) >135 (mEq/L) 133381 (92.9%) 129497 (92.82%) b Hematocrit (%) 40.73 ± 4.06 40.72 ± 4.06 no anemia 125154 (84.6%) 121526 (84.55%) mild anemia 22,056 (14.9%) 21481 (14.95%) moderate-severe anemia 749 (0.5%) 726 (0.51%) PTT 29.16 ± 4.63 29.16 ±4.63 a BMI classification was adapted from the World Health organization (WHO) global database16 b Anemia was defined using the WHO sex based criteria17
0.6437 0.5041 <0.0001 <0.0001 0.9575 0.0252 0.1464 0.0003 0.5226 0.0188 0.006 0.0007 0.0008 0.0026 0.0146 <0.0001 0.0529
0.3167
ACCEPTED MANUSCRIPT
Table 2. Complications
Unilateral TKA (n=150581) N %
SBTKA
Unadjusted
Adjusted
(n=4441) N %
OR (95% CI)
p-value 0.4956
OR (95% CI)
p-value
<0.0001 <0.0001 0.001 <0.0001
3.95 (3.65-4.27) 1.97 (1.64-2.37) 1.18 (0.92-1.51) 1.48 (1.30-1.67)
<0.0001 <0.0001 0.1929 <0.0001
0.11
6
0.14
1.23 (0.55-2.79)
11448 2185 1731 6980
7.6 1.45 1.15 4.64
1128 121 75 305
25.4 2.72 1.69 6.87
4.14 (3.86-4.44) 1.90 (1.58-2.29) 1.48 (1.17-1.87) 1.52 (1.35-1.71)
Cardiac complicationsb Pneumonia Intubationc Urinary tract Infection Acute Renal Failure Progressive Renal Insufficiency
408 530 247 1369 94 180
0.27 0.35 0.16 0.91 0.06 0.12
13 18 14 68 2 12
0.29 0.41 0.32 1.53 0.05 0.27
1.08 (0.62-1.88) 1.15 (0.72-1.85) 1.93 (1.12-3.30) 1.70 (1.33-2.17) 0.72 (0.18-2.93) 2.26 (1.26-4.06)
0.7834 0.555 0.0238 <0.0001 1 0.0049
1.76 (0.99-3.15) 1.70 (1.31-2.20)
0.0556 <0.0001
2.71 (1.50-4.88)
0.0009
CVA Wound complicationsd Superficial Surgical Site infection
127 1443 826
0.08 0.96 0.55
5 49 24
0.11 1.1 0.54
1.34 (0.55-3.27) 1.15 (0.87-1.54) 0.99 (0.66-1.48)
0.4333 0.3109 0.9424
0.93 (0.69-1.25)
0.6264
0.19
9
0.2
1.05 (0.54-2.04)
0.8882
0.28
20
0.45
1.60 (1.02-2.51)
0.039
1.10 (0.68-1.77)
0.6921
Wound dehiscence
291
Deep infection
425
e
SC
M AN U
TE D
Bleeding Thromboembolism Return to OR Composite morbiditya
RI PT
165
Mortality
AC C
EP
Sepsis 403 0.27 20 0.45 1.69 (1.08-2.64) 0.0214 1.30 (0.80-2.10) 0.2905 Composite morbidity includes thromboembolism, cardiac complications, pneumonia, intubation >48 hrs, unplanned intubation, urinart tract infection, acute renal failure, progressive renal insufficiency, CVA, superficial surgical Site infection, wound dehiscence, deep infection and sepsis b Cardiac Complications include myocardial infarction and/or cardiac arrest requiring CPR c Intubation includes unplanned intubation and/or intubation more than 48 hours d Wound complications include Superficial surgical site infection, wound dehiscence and deep surgical site infection e Sepsis includes sepsis and septic shock a
ACCEPTED MANUSCRIPT
P Value
Adjusted OR (95% CI)
P Value
% 2.72
1.90 (1.58-2.29)
<0.0001
1.97 (1.64-2.37)
<0.0001
48 73
2.56 2.85
1.87 (1.39-2.51) 1.94 (1.53- 2.46)
< 0.0001 < 0.0001
1.99 (1.48- 2.69) 2.04 (1.60- 2.59)
< 0.0001 < 0.0001
1.28 1.55 1.95
61 58 2
2.69 2.7 7.14
2.13 (1.63- 2.77) 1.76 (1.35- 2.30) 3.88 (0.90- 16.69)
< 0.0001 < 0.0001 0.106
2.15 (1.65- 2.80) 1.81 (1.39- 2.36) 4.25 (0.98-18.38)
< 0.0001 < 0.0001 0.0528
1875 248 38 24
1.41 2 1.04 1.63
99 17 5 0
2.52 5.2 3.52 0
1.81 (1.47- 2.22) 2.69 (1.63- 4.46) 3.48 (1.35- 8.98) N/A
< 0.0001 < 0.0001 0.0208 1
1.86 (1.51- 2.28) 3.10 (1.85- 5.22) 3.48 (1.35- 8.98) N/A
< 0.0001 < 0.0001 0.0099
3 169 591
0.82 1.13 1.44
30-34.9 (n=44407) 35-39.9 (n=29191)
657 444
1.52 1.57
≥40 (n=23513)
321
No (n=127168) Yes (n=27854) Smoking No (n=141824)
Diabetes
Yes (n=13198) ASA class
n 121
781 1404
1.39 1.49
781 1342 62
SC
% 1.45
M AN U
n 2185
0 9 31
0 2.33 2.57
N/A 2.08 (1.06- 4.10) 1.81 (1.25- 2.61)
1 0.0473 0.0013
N/A 1.73 (0.84- 3.57) 1.96 (1.36- 2.83)
0.138 0.0003
EP
Age <65 (n=63070) 65-85 (n=88738) >85 (n=3214) Race White (n=136950) Black (n=12757) Asian (n=3803) Other (n=1512) BMI <18.5 (n=377) 18.5-24.9 (n=15288) 25-29.9 (n=42246)
SBTKA
42 23
3.25 2.55
2.17 (1.58- 2.98) 1.64 (1.08- 2.51)
< 0.0001 0.0206
2.75 (1.96- 3.85) 1.70 (1.11- 2.60)
< 0.0001 0.0148
1.4
16
2.48
1.79 (1.08- 2.97)
0.0232
1.70 (1.02- 2.85)
0.0425
1799 386
1.46 1.42
103 18
2.73 2.78
1.90 (1.55- 2.32) 1.93 (1.19- 3.11)
< 0.0001 0.0063
1.97 (1.61- 2.40) 2.01 (1.25- 3.25)
< 0.0001 0.0043
2013
1.46
112
2.74
1.90 (1.57- 2.30)
< 0.0001
1.97 (1.63- 2.39)
< 0.0001
172
1.34
9
2.54
1.92 (0.98- 3.79)
0.0623
1.98 (1.00- 3.90)
0.0496
AC C
Thromboembolism (All) Gender Male (n=58188) Female (n=96834)
Unilateral TKA
RI PT
Unadjusted OR (95% CI)
TE D
Table 3. Stratification of Patients with Thromboembolism
ACCEPTED MANUSCRIPT
CHF (within 30 days) No (n=154633) Yes (n=389) Dyspnea No (n=145195) Yes (n=9827) Transfusion before surgery No (n=154951) Yes (n=71) Preop INR ≤1.2 (n=151893) >1.2 (n=3129)
< 0.0001 0.0005
2.13 (1.68- 2.70) 1.79 (1.33- 2.42)
< 0.0001 0.0001
1106 879
1.46 1.45
73 31
2.66 2.36
1.85 (1.45- 2.35) 1.65 (1.15- 2.37)
< 0.0001 0.0063
1.91 (1.50- 2.43) 1.73 (1.21- 2.49)
< 0.0001 0.003
200
1.43
17
4.39
3.18 (1.92- 5.27)
< 0.0001
3.70 (2.20- 6.19)
< 0.0001
2153 29
1.45 1.22
119 2
2.71 4.55
1.89 (1.57- 2.27) 3.86 (0.89- 16.69)
< 0.0001 0.1077
1.95 (1.62- 2.36) 3.88 (0.89- 16.89)
< 0.0001 0.0707
3
3.45
0
0
N/A
0.8501
N/A
2109 76
1.44 2.09
119 2
1833 307 45
1.46 1.4 1.44
48 47 26
2180 5
1.45 1.3
1998 187
1.42 1.94
RI PT
2.09 (1.65- 2.65) 1.70 (1.26- 2.29)
SC
Bleeding disorder No (n=151305) Yes (n=3717) Operative time <120 min (n=126936) 120-179 min (n=23912) ≥180 min (n=4174)
2.82 2.59
M AN U
Dependent (n=88)
75 46
2.73 2.38
1.93 (1.60- 2.33) 1.14 (0.28- 4.73)
< 0.0001 0.696
2.01 (1.66- 2.42) 1.13 (0.27- 4.68)
< 0.0001 0.8716
3.31 2.42 2.48
2.31 (1.73- 3.09) 1.75 (1.28- 2.39) 1.74 (1.07- 2.83)
< 0.0001 < 0.0001 0.0244
2.35 (1.76- 3.15) 1.86 (1.36- 2.54) 1.74 (1.07- 2.83)
< 0.0001 < 0.0001 0.0262
TE D
Others (n=14418) Functional health status Independent (n=152513) Partially dependent (n=2421)
1.37 1.54
2.73 0
1.74 (1.07- 2.83) N/A
< 0.0001 1
1.97 (1.64- 2.37) N/A
< 0.0001
114 7
2.69 3.5
1.92 (1.59- 2.33) 1.83 (0.85- 3.95)
< 0.0001 0.1189
1.98 (1.64- 2.40) 1.98 (0.92- 4.29)
< 0.0001 0.0819
121 0
EP
Type of anesthesia General (n=78551) Spinal/Epidural (n=62053)
1073 1112
AC C
I - II (n=81145) III - V (n=73877)
2185 0
1.45 0
121 0
2.73 0
1.90 (1.58- 2.29)
< 0.0001
1.97 (1.64- 2.37)
< 0.0001
2137 48
1.45 1.56
119 2
2.72 3.39
1.90 (1.58- 2.29) 2.21 (0.52- 9.31)
< 0.0001 0.2428
1.97 (1.64- 2.38) 2.29 (0.54- 9.67)
< 0.0001 0.2606
ACCEPTED MANUSCRIPT
Table 4. Stratification of Patients with Bleeding P Value
Adjusted OR (95% CI)
P Value
% 25.4
4.14 (3.86-4.44)
<0.0001
3.95 (3.65-4.27)
<0.0001
383 745
20.39 29.07
3.75 (3.34- 4.22) 4.51 (4.13- 4.93)
< 0.0001 < 0.0001
3.90 (3.42- 4.45) 3.98 (3.60- 4.39)
< 0.0001 < 0.0001
5.88 8.45 17.33
516 599 13
22.79 27.87 46.43
4.72 (4.26- 5.24) 4.19 (3.80- 4.61) 4.14 (1.96- 8.74)
< 0.0001 < 0.0001 < 0.0001
4.00 (3.56- 4.49) 3.89 (3.49- 4.33) 5.64 (2.59- 12.29)
< 0.0001 < 0.0001 < 0.0001
10015 1104 285 44
7.53 8.88 7.78 2.98
992 97 35 4
4.14 (3.84- 4.46) 4.33 (3.39- 5.53) 3.88 (2.60- 5.78) 3.94 (1.34- 11.61)
< 0.0001 < 0.0001 < 0.0001 0.0274
3.92 (3.60- 4.26) 4.15 (3.16- 5.44) 4.03 (2.59- 6.27) 5.15 (1.69- 15.72)
< 0.0001 < 0.0001 < 0.0001 0.004
53 1769 3577
14.56 11.87 8.72
30.77 31.35 27.39
2.61 (0.78- 8.77) 3.39 (2.72- 4.23) 3.95 (3.46- 4.50)
0.117 < 0.0001 < 0.0001
4.39 (1.22- 15.79) 3.37 (2.64- 4.30) 3.90 (3.36- 4.52)
0.0234 < 0.0001 < 0.0001
30-34.9 (n=44407) 35-39.9 (n=29191)
3029 1763
7.03 6.23
318 208
24.63 23.09
4.33 (3.79- 4.94) 4.52 (3.84- 5.31)
< 0.0001 < 0.0001
4.11 (3.54- 4.76) 4.12 (3.44- 4.95)
< 0.0001 < 0.0001
≥40 (n=23513)
1257
5.5
147
22.79
5.08 (4.19- 6.15)
< 0.0001
4.13 (3.33- 5.13)
< 0.0001
No (n=149761) Yes (n=5261)
10980 468
7.55 9.13
1092 36
25.37 26.28
4.16 (3.88- 4.47) 3.55 (2.40- 5.25)
< 0.0001 < 0.0001
3.95 (3.64- 4.28) 3.93 (2.55- 6.08)
< 0.0001 < 0.0001
ASA class I - II (n=81145) III - V (n=73877)
5014 6434
6.39 8.92
653 475
24.52 26.72
4.76 (4.34- 5.22) 3.72 (3.34- 4.15)
< 0.0001 < 0.0001
4.18 (3.76- 4.64) 3.68 (3.26- 4.15)
< 0.0001 < 0.0001
Steroid Use
n 1128
3600 7848
6.36 8.32
3577 7319 552
25.21 29.66 24.65 10.81
TE D
EP
4 121 330
SC
% 7.6
M AN U
n 11448
AC C
Age <65 (n=63070) 65-85 (n=88738) >85 (n=3214) Race White (n=136950) Black (n=12757) Asian (n=3803) Other (n=1512) BMI <18.5 (n=377) 18.5-24.9 (n=15288) 25-29.9 (n=42246)
SBTKA
RI PT
Unadjusted OR (95% CI)
Bleeding (ALL) Gender Male (n=58188) Female (n=96834)
Unilateral TKA
ACCEPTED MANUSCRIPT
29.97 16.86
4.47 (4.10- 4.87) 2.97 (2.56- 3.45)
< 0.0001 < 0.0001
4.53 (4.11- 5.00) 2.71 (2.31- 3.19)
< 0.0001 < 0.0001
942
6.71
85
21.96
3.91 (3.05- 5.02)
< 0.0001
4.42 (3.39- 5.76)
< 0.0001
11014 434
7.5 11.95
1099 29
25.22 34.52
4.16 (3.88- 4.47) 3.89 (2.45- 6.16)
< 0.0001 < 0.0001
3.96 (3.66- 4.29) 3.38 (1.99- 5.76)
< 0.0001 < 0.0001
9125 1870 453
7.27 8.51 14.5
356 464 308
24.57 23.88 29.36
4.15 (3.68- 4.69) 3.37 (3.01- 3.78) 2.45 (2.08- 2.90)
< 0.0001 < 0.0001 < 0.0001
4.73 (4.17- 5.37) 3.94 (3.49- 4.45) 2.89 (2.42- 3.45)
< 0.0001 < 0.0001 < 0.0001
3351 8097
6.56 8.14
420 708
7287 3928 233
5.68 18.28 32.05
850 269 9
11423 25
7.59 37.31
11100 348
7.52 11.34
1124 4 1116 12
M AN U
SC
RI PT
822 221
24.36 26.06
4.59 (4.09- 5.15) 3.98 (3.64- 4.35)
< 0.0001 < 0.0001
3.92 (3.44- 4.46) 3.96 (3.59- 4.38)
< 0.0001 < 0.0001
22.13 46.62 39.13
4.72 (4.36- 5.11) 3.91 (3.30- 4.62) 1.36 (0.58- 3.20)
< 0.0001 < 0.0001 0.4745
4.10 (3.75- 4.48) 3.53 (2.95- 4.23) 1.37 (0.52-3.60)
< 0.0001 < 0.0001 0.5269
25.33 100
4.13 (3.85- 4.43) N/A
< 0.0001 0.0244
3.95 (3.65- 4.27)
< 0.0001
25.47 20.34
4.20 (3.91- 4.51) 2.00 (1.05- 3.80)
< 0.0001 0.0318
3.98 (3.68- 4.31) 2.51 (1.29- 4.87)
< 0.0001 0.0067
TE D
Hypertension No (n=52802) Yes (n=102220) Preop Hct no anemia (n=132204) mild anemia (n=22068) moderate-severe anemia (n=750) Transfusion before surgery No (n=154951) Yes (n=71) Preop INR ≤1.2 (n=151893) >1.2 (n=3129)
8.74 6.39
EP
Others (n=14418) Bleeding disorder No (n=151305) Yes (n=3717) Operative time <120 min (n=126936) 120-179 min (n=23912) ≥180 min (n=4174)
6627 3879
AC C
Type of anesthesia General (n=78551) Spinal/Epidural (n=62053)
S0883-5403(18)30552-7
DOI:
10.1016/j.arth.2018.06.002
Reference:
YARTH 56659
To appear in:
The Journal of Arthroplasty
Received Date: 15 February 2018 Revised Date:
29 May 2018
Accepted Date: 1 June 2018
Please cite this article as: Masrouha KZ, Hoballah JJ, Tamim H, Sagherian BH, Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral versus unilateral total knee arthroplasty, The Journal of Arthroplasty (2018), doi: 10.1016/j.arth.2018.06.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Original article
RI PT
Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral versus unilateral total knee arthroplasty Karim Z. Masrouha, MD1, Jamal J. Hoballah, MD2, Hani Tamim, MPH, PhD3, Bernard H. Sagherian, MD1
SC
Investigation performed at the Division of Orthopaedic Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon
1
M AN U
Division of Orthopaedic Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon 2
Division of Vascular Surgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon
3
TE D
Biostatistics Unit in the Clinical Research Institute, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Correspondence and reprints:
AC C
EP
Bernard H. Sagherian, MD Assistant Professor of Orthopaedic Surgery Division of Orthopaedic Surgery Department of Surgery American University of Beirut Medical Center P.O.Box 11-0236 Riad El-Solh Beirut 1107 2020 Lebanon Tel: + 961 (1) 350000, ext 5444 Fax: +961 (1) 363291 Email: [email protected]
ACCEPTED MANUSCRIPT 1 Original article Comparing the 30-day risk of venous thromboembolism and bleeding in simultaneous bilateral versus unilateral total knee arthroplasty
RI PT
1 2 3 4 5 6 7 8 9
Abstract
Background: Simultaneous bilateral total knee arthroplasty (SBTKA) may offer certain benefits,
11
however its overall safety is still disputed. This study aimed to compare the risk of
12
thromboembolism and bleeding in patients who underwent SBTKA versus unilateral total knee
13
arthroplasty (TKA).
14
Methods: The American College of Surgeons – National Quality Improvement Program (ACS-
15
NSQIP) database from 2008 – 2015 was used to investigate the short-term postoperative
16
complications and their risk factors following SBTKA as compared to unilateral TKA.
17
Demographics, comorbidities, and 30-day outcomes were analyzed. Complications with an
18
increased incidence following SBTKA were stratified to identify subgroups of patients at high
19
risk.
20
Results: Total of 155,022 patients were identified, of which 150,581 underwent unilateral TKA
21
and 4,441 underwent SBTKA. The SBTKA group was found to be at a higher risk for venous
22
thromboembolism (VTE), bleeding, and composite morbidity. Stratification analysis revealed
23
that SBTKA subgroups at higher risk for VTE include patients of black or Asian origin, obese
24
patients and those who underwent anesthesia other than general or spinal / epidural. SBTKA
25
subgroups at higher risk for bleeding include patients older than 85 years, those with race other
26
than white, underweight and obese patients, and patients who underwent anesthesia other than
27
spinal / epidural. Although none of the subgroups were protected from bleeding, patients who
AC C
EP
TE D
M AN U
SC
10
ACCEPTED MANUSCRIPT 2 underwent spinal / epidural anesthesia had a lower risk for bleeding compared to other types of
29
anesthesia.
30
Conclusion: SBTKA confers an increased risk of postoperative VTE, bleeding and composite
31
morbidity at 30 days, with no increase in mortality.
32 33 34
Keywords
35
complications; risk factors
RI PT
28
AC C
EP
TE D
M AN U
SC
Thromboembolism; bleeding; bilateral knee arthroplasty; unilateral knee arthroplasty;
ACCEPTED MANUSCRIPT 3 36
Introduction
37 The safety and cost-effectiveness of simultaneous bilateral total knee arthroplasty (SBTKA)
39
compared to a staged procedure continues to be a matter of debate as evidenced by the number of
40
recent studies published in the literature. There are no level 1 prospective studies addressing this
41
issue and most of the literature relies on single-center retrospective analyses or population-based
42
studies which have shown that SBTKA decreases costs but may increase perioperative morbidity
43
and mortality [1-9]. However, not all studies have looked into specific morbidities nor have they
44
attempted to identify subgroups of patients that might be at increased risk for specific
45
complications when undergoing SBTKA compared to a unilateral procedure[10-15] .
46
The American College of Surgeons – National Surgical Quality Improvement Program (ACS-
47
NSQIP) dataset has been used to better understand the 30-day outcomes of surgical procedures
48
and help participating hospitals identify perioperative risk factors and develop guidelines to
49
decrease the rate of complications and adverse events[16]. It has recently been used to look into
50
outcomes following SBTKA as compared to unilateral TKA [10, 11]. These studies have
51
analyzed overall and major complications as well as 30-day readmission rates and mortality as
52
outcomes. They have either failed to show an increased risk of thromboembolism and bleeding
53
in patients undergoing SBTKA versus unilateral TKA [11] or have not specifically analyzed
54
these complications[10]. Moreover they have not attempted stratification of specific
55
complications to identify subgroups of patients within the SBTKA group who might be at even
56
higher risk for specific complications compared to the unilateral TKA group. Rather they have
57
grouped all the complications and analyzed independent predictors on major complications. We
58
therefore sought to use the ACS-NSQIP database to analyze specific complications for which
AC C
EP
TE D
M AN U
SC
RI PT
38
ACCEPTED MANUSCRIPT 4 59
patients who undergo SBTKAs are at an increased risk compared to unilateral TKA and to
60
further stratify the relevant variables and identify subgroups of patients that are at increased risk
61
of developing such complications.
63
RI PT
62 Materials and Methods
64 Study design
SC
65 66
This was a retrospective cohort study using data from the ACS-NSQIP database. The ACS-
68
NSQIP dataset includes over 135 variables collected on surgical patients from 696 centers across
69
the United States and worldwide, including Saudi Arabia, Canada,
70
Lebanon, United Kingdom, and the United Arab Emirates, and has information on 30-day
71
morbidity and mortality along with other various demographics. Specially trained personnel at
72
every collaborating institution collect de-identified medical information and log it into the
73
databank [17]. In accordance with our institutional guidelines, which follow the US Code of
74
Federal Regulations for the Protection of Human Subjects, Institutional Review Board approval
75
was not needed for our analysis because data were de-identified and collected as part of a quality
76
assurance activity.
78 79
TE D
EP
AC C
77
M AN U
67
Patient selection
80
Data from 2008 through 2015 were queried to identify patients who underwent unilateral TKA or
81
SBTKA performed under the same anesthesia using the current procedural terminology (CPT)
ACCEPTED MANUSCRIPT 5 code 27447. Patients who had other concurrent or concomitant procedures were excluded. Uni-
83
compartmental knee arthroplasty, CPT code 27446, was not included in the query. NSQIP
84
variables were used to exclude patients with disseminated cancer, those who underwent
85
emergency procedures or had an open wound and/or wound infection. ICD9 and ICD10 codes
86
were used to exclude patients who underwent total knee arthroplasty with arthropaties associated
87
with infection, osteomyelitis, malignant neoplasms and fractures.
88
Patient demographics, comorbidities, and selected laboratory values were obtained from the
89
ACS-NSQIP database as baseline characteristics (Table 1). These included age, gender, race,
90
American Society of Anesthesiology (ASA) classification, total operative time, functional status,
91
body mass index (BMI), tobacco use, diabetes mellitus, hypertension, steroid use, chronic
92
obstructive pulmonary disease (COPD), congestive heart failure (CHF), dyspnea, renal failure on
93
dialysis, anesthesia type, transfusion before surgery, bleeding disorders, prothrombin time (PTT),
94
international normalized ratio (INR), platelet count, white blood cell count, hematocrit (Hct), and
95
serum sodium levels. The BMI classification was adapted from the World Health organization
96
(WHO) global database[18]. Anemia was defined using the WHO sex based criteria[19].
97
Thirty-day mortality and morbidity, including cardiac, wound, respiratory, urinary tract, central
98
nervous system, sepsis, venous thromboembolism (VTE), bleeding, mortality, and return to the
99
operating room were recorded as adverse events. Venous thromboembolism was defines as deep
100
venous thrombosis and/or pulmonary embolism. Bleeding is defined in the NSQIP as red blood
101
cell (RBC) transfusion intraoperative / postoperative within the first 72 hours of surgery start
102
time. Variables with more than 20% missing data were removed from the analysis.
SC
M AN U
TE D
EP
AC C
103 104
RI PT
82
Statistical analysis
ACCEPTED MANUSCRIPT 6 105 Statistical analyses were done using Statistical Analysis System (SAS) software (version 9.1;
107
SAS Institute, Cary, North Carolina). Categorical variables were presented as number and
108
percentage, whereas continuous ones as mean and standard deviation. Continuous variables were
109
compared using the independent t-test and categorical variables using the Chi-square test. Odds
110
ratios (OR) for mortality and morbidities were calculated, using logistic regression with 95%
111
confidence intervals (CI). An initial univariate analysis was done to analyze the effect of SBTKA
112
on mortality and other postoperative complications (Table 2). Relevant confounders for specific
113
complications were controlled for (see Appendix 1) and a multivariate logistic regression
114
analysis was performed to detect the independent effect of the type of surgery, SBTKA or
115
unilateral TKA, on complications that were significant on initial analysis. Complications for
116
which SBTKA was found to be an independent risk factor were further analyzed by subgroup
117
stratification to identify specific subgroups of patients that might be at an even higher risk for
118
that specific complication. The level of significance for p-value was < 0.05.
119
121
Results
EP
120
TE D
M AN U
SC
RI PT
106
A total of 155,022 patients were identified, of which 150,581 underwent unilateral TKA (97.1%)
123
and 4,441 underwent SBTKA (2.9%). Table 1 shows the baseline characteristics of each group.
124
There were several statically significant differences between the baseline characteristics of the
125
two groups. Patients who underwent SBTKA were more likely to be younger than 65 years old
126
(50.98% versus 40.38% P < 0.0001), male (42.35% versus 37.42% P < 0.0001), have a lower
127
ASA classification (59.88% versus 52.08% P < 0.0001), have a longer mean operative time (149
AC C
122
ACCEPTED MANUSCRIPT 7 minutes ± 54.70 versus 92 minutes ± 36.39 P < 0.0001), undergo general anesthesia more
129
frequently (61.76% versus 50.34% P < 0.0001), have a higher preoperative Hct (41.03% ± 4.13
130
versus 40.72% ± 4.06 P < 0.0001), and lower mean serum creatinine (mg/dL) levels (0.88
131
mg/dL ± 0.32 versus 0.92 mg/dL ± 0.41 P < 0.0001). SBTKA patients were less likely to have
132
diabetes on oral medications or insulin (15.02% versus 18.05% P < 0.0001), hypertension on
133
medications (61.18% versus 66.08% P < 0.0001), severe chronic obstructive pulmonary disease
134
(COPD) (2.3% versus 3.59% P < 0.0001), congestive heart failure (CHF) (0.09% versus 0.26%
135
P = 0.0297), dyspnea (4.5% versus 6.39% P < 0.0001) or an international normalized ratio
136
(INR) of more than 1.2 (2.01% versus 3.08% P = 0.0008).
137
Regarding the 30-day outcomes, the SBTKA group was at a higher risk for developing VTE (OR
138
1.97, 95% CI: 1.64-2.37), bleeding (OR 3.95, 95% CI: 3.65-4.27), composite morbidity (OR
139
1.48, 95% CI: 1.30-1.67), progressive renal insufficiency (OR 2.71, 95% CI: 1.50-4.88) and
140
urinary tract infection (OR 1.70, 95% CI: 1.31-2.20). Multivariate logistic regression analysis
141
showed no statistically significant differences between the two groups in terms of mortality,
142
cardiac complications (myocardial infarction and cardiac arrest necessitating CPR), pneumonia,
143
prolonged or unplanned intubations, acute renal failure, cerebrovascular accidents or wound
144
complications, whether superficial or deep. There was also no difference in return to the
145
operating room between the two groups after adjusting for confounders (Table 2).
146
Upon stratification of different baseline characteristics in patients who had a VTE, several
147
subgroups were at a risk higher than the baseline adjusted odds ratio of 1.97 (95% CI: 1.64-2.37)
148
when undergoing SBTKA compared to unilateral TKA. These included patients who are black
149
(OR 3.10, 95% CI: 1.85- 5.22, P < 0.0001), Asian (OR 3.48, 95% CI: 1.35- 8.98, P = 0.0099),
150
have a BMI between 30 and 34.9 Kg/m2 (OR 2.75, 95% CI: 1.96- 3.85, P < 0.0001), are diabetic
AC C
EP
TE D
M AN U
SC
RI PT
128
ACCEPTED MANUSCRIPT 8 (OR 2.01, 95% CI: 1.25- 3.25, P = 0.0043), or underwent anesthesia other than general or spinal
152
/ epidural (OR 3.70, 95% CI: 2.20- 6.19, P < 0.0001). Patients without a bleeding disorder were
153
particularly at an increased risk for VTE (OR 2.01, 95% CI: 1.66- 2.42, P < 0.0001). Operative
154
time of more than 120 minutes did not confer any increased risk for VTE compared to operative
155
times of less than 120 minutes. Patient subgroups that showed an increased risk of VTE when
156
undergoing SBTKA without reaching statistical significance include patients older than 85 years,
157
those with partial functional dependence. This might be due to the limited occurrence of these
158
variables in the SBTKA group (Table 3).
SC
RI PT
151
Subgroups of patients undergoing SBTKA who were at a higher risk for bleeding than the
160
baseline adjusted odds ratio of 3.95 (95% CI: 3.65-4.27) compared to the unilateral TKA
161
counterparts included patients older than 85 years (OR 5.64, 95% CI: 2.59- 12.29, P < 0.0001),
162
those who are black, Asian or of origins other than white, black or Asian, those with BMI <18.5
163
or >30 Kg/m2, patients who underwent general anesthesia or anesthesia other than spinal /
164
epidural. Patients with operative times < 120 minutes and those with no preoperative anemia
165
were also at a higher risk for bleeding. Patients with an INR >1.2 preoperatively had a risk for
166
bleeding (OR 2.51, 95% CI: 1.29- 4.87, P = 0.0067) lower than those with an INR ≤ 1.2 (OR
167
3.98, 95% CI: 3.68- 4.31, P < 0.0001). Similar findings of lower risks of bleeding were found in
168
patients who underwent spinal/epidural anesthesia (OR 2.71, 95% CI: 2.31- 3.19, P < 0.0001)
169
compared to other types of anesthesia, or had an operative time of more than 180 minutes (OR
170
2.89, 95% CI: 2.42- 3.45, P < 0.0001) (Table 4).
172
TE D
EP
AC C
171
M AN U
159
Discussion
ACCEPTED MANUSCRIPT 9 The aim of our study was to evaluate whether SBTKA was a risk factor for various
174
complications within the 30 postoperative days compared to unilateral TKA and to analyze
175
whether there are specific subgroups of patients that are at higher risk for certain complications.
176
SBTKA was found to be a risk factor for thromboembolism, bleeding, urinary tract infection,
177
progressive renal insufficiency and composite morbidity. After adjusting for baseline
178
characteristics the SBTKA group had twice the risk of VTE and almost four times the risk of
179
bleeding compared to the unilateral TKA group. The increased risk persisted across most of the
180
stratification analysis, and none of the subgroups was protected from VTE or bleeding when
181
undergoing SBTKA versus unilateral TKA. Although none of the variables was protective
182
against VTE or bleeding, certain characteristics conferred a higher increase in the risks of VTE
183
and bleeding, while others carried a slightly lower risk for these complications (Tables 3 and 4).
184
In our study SBTKA was not associated with an increased risk of mortality [unadjusted OR 1.23
185
(0.55-2.79) P = 0.4956], return to operating room [OR 1.18 (0.92-1.51) P = 0.1929], cardiac
186
complications or wound infections compared to unilateral TKA.
TE D
M AN U
SC
RI PT
173
Although the majority of patients with knee osteoarthritis suffer from bilateral disease
188
[20], less than 3% of patients in the ACS-NSQIP database underwent a bilateral procedure,
189
which is commensurate with numbers found in the literature [5, 7]. This is understandable given
190
the amount of recent literature that has found an increase in morbidity and mortality in those
191
undergoing a SBTKA [3, 4, 21]. However, there are data, which suggest that, after matching for
192
baseline characteristics, SBTKA may be associated with lower costs and better outcomes,
193
including prosthesis survival, lower infection rates and no difference in perioperative
194
complications.[5, 6, 22-25]. Additionally, patient reported outcomes favor performing a SBTKA
195
versus a staged procedure [26]. The statement from the consensus conference on SBTKA
AC C
EP
187
ACCEPTED MANUSCRIPT 10 196
showed that 81% of participants agreed that this procedure is associated with an increased risk of
197
perioperative complications in unselected patients. They suggested that hospitals should have
198
stricter criteria to exclude patients with increased cardiac risk factors [27]. Several studies have tried to identify risk factors associated with mortality and morbidity
200
in SBTKA in attempts to establish patient selection criteria. These risk factors include old age[4,
201
28-33], male sex[4, 28, 29], preoperative cardiac disease[28, 34-37] and pulmonary
202
comorbidities[33].
SC
RI PT
199
Two recent studies from the ACS-NSQIP database have matched patients in each of the
204
SBTKA and unilateral TKA groups to prevent selection bias [10, 11]. They have found that
205
those who underwent a SBTKA had an increased risk for postoperative major medical
206
complications as well as return to the operating room, but no differences in infection rates,
207
readmission rates, or mortality. However, they have failed to perform a multivariate analysis to
208
confirm that SBTKA is an independent risk factor for return to the operating room. Our analysis
209
showed similar results, although the increased risk for return to the operating room did not
210
persist after adjusting for confounders. We also found an increased risk for VTE and bleeding,
211
which were not specifically studied or stratified in these studies. These findings are in
212
contradistinction to previous studies that have suggested an increased risk of mortality in patients
213
undergoing a SBTKA [3, 4, 21, 38]. Other studies have reported increased rates of myocardial
214
infarction, postoperative confusion, and the need for intensive monitoring after SBTKA
215
compared to unilateral TKA, however, with similar 30 day and one year mortality rates and
216
similar risks of pulmonary embolism, infection, and deep venous thrombosis for the two
217
groups.[30]
AC C
EP
TE D
M AN U
203
ACCEPTED MANUSCRIPT 11 A cohort analysis from the Canadian Hospital Morbidity Database showed higher rates of
219
transfusion in patients who underwent SBTKA (41%) as compared to a unilateral TKA (13.3%)
220
or the second knee in a staged procedure (18.6%) [2]. This could correspond to the increased risk
221
of postoperative bleeding in patients undergoing SBTKA in the present study, and the results
222
from a previous ACS-NSQIP study [10]. Although the ACS-NSQIP does not provide
223
information regarding the use of drains, two recent studies have shown that there are no
224
differences in postoperative bleeding or clinical outcomes, with or without the use of a drain [39,
225
40]. A recent meta-analysis on the use of tranexamic acid in patients undergoing SBTKA
226
showed favorable outcomes with regards to postoperative hemoglobin, drainage volume,
227
transfusion rate, and number of units transfused, without any increased risk of VTE[41].
228
Therefore, the increased risk of bleeding may be decreased with the use of tranexamic acid in
229
patients undergoing SBTKA. Data regarding the use of tranexamic acid was not included in the
230
ACS-NSQIP.
TE D
M AN U
SC
RI PT
218
In the study by Hart et al. the unadjusted rate of pulmonary embolism was higher in
232
SBTKA (1.4%) versus unilateral TKA (0.7%) [10]. Two previous large studies have shown
233
similar findings, as well as ORs similar to those of the present study during the first three months
234
postoperatively [42, 43]. Although there are data to suggest that this increased risk is similar,
235
whether patients undergo simultaneous or staged procedures[2, 44], other studies have found that
236
simultaneous procedures have an increased risk of VTE as compared to staged procedures [3,
237
43]. As with our study, Bohm et al. found that male sex, age more than 75 years, and at least one
238
comorbidity, were at increased risk of pulmonary embolism [2]. Furthermore, there is no
239
consensus on the length of time between the first and second surgeries of a staged bilateral TKA.
240
While one study found staggered bilateral total knee replacement, performed four to seven days
AC C
EP
231
ACCEPTED MANUSCRIPT 12 241
apart in a single hospitalization, to have significantly lower rate of complications compared to
242
SBTKA[45], another study found procedures separated by the same period of time to have
243
similar complication profiles compared to SBTKA.[46] A significant finding in our study was the lower risk of bleeding and VTE in the
245
subgroup of patients undergoing SBTKA under spinal / epidural anesthesia compared to general
246
or other forms of anesthesia. SBTKA was an independent risk factor for bleeding OR 3.95 (95%
247
CI: 3.65-4.27, P <0.0001), however in the subgroup of spinal / epidural anesthesia the risk was
248
2.71 (95% CI: 2.31-3.19, P < 0.0001). Similar results of lower percentage of SBTKA patients
249
requiring transfusion under neuraxial anesthesia was reported by Stundner et al in a national
250
database analysis [47]. However the same study did not find any decreased risk of pulmonary
251
embolism using neuraxial anesthesia for SBTKA patients. Our study is the first to demonstrate
252
that the risk of thromboembolism in the subgroup of patients undergoing SBTKA under spinal /
253
epidural anesthesia is lower compared to those undergoing the same procedure under general
254
anesthesia. Whereas SBTKA had a twofold risk of thromboembolism compared to unilateral
255
TKA (OR 1.97, 95% CI: 1.64-2.37, P <0.0001), in the subgroup of patients undergoing spinal /
256
epidural anesthesia SBTKA was still a risk factor for thromboembolism however to a lesser
257
degree (OR 1.73, 95% CI: 1.21-2.49, P = 0.003).
SC
M AN U
TE D
EP
Other significant findings after subgroup stratification in the current study include the
AC C
258
RI PT
244
259
increased risk of VTE in patients of black or Asian origin undergoing SBTKA. Although
260
SBTKA was found to be an independent risk factor for this complication (OR 1.97, 95% CI:
261
1.64-2.37, P < 0.0001), patients of black and Asian race were at a much higher risk of VTE with
262
OR of 3.10 (95% CI: 1.85- 5.22,) and 3.48 (95% CI: 1.35- 8.98), respectively, when undergoing
263
SBTKA rather than a unilateral procedure. This finding highlights the importance of race to be
ACCEPTED MANUSCRIPT 13 considered when counseling patients for SBTKA. In a population study in California, SooHoo et
265
al. have shown that black race is associated with a 73% increased rate of pulmonary embolism in
266
patients undergoing total knee arthroplasty compared to white counterparts. The increased risk of
267
VTE in black race and decreased risk in Asians is reported in several studies [48, 49]. This is in
268
contrast to the findings in our study where the subgroup of patients of Asian origin had an
269
increased risk of VTE when undergoing SBTKA.
RI PT
264
Although a recent NSQIP study has shown that an increase in surgical duration to be
271
directly associated with an increase in the risk of VTE [50], increase in operative time did not
272
increase the risk of VTE in SBTKA patients compared to their unilateral TKA counterparts. In
273
contrast the subgroup of patients with an operative time < 120 minutes had the higher risk of
274
VTE. While this finding was statistically significant, it should not be assumed that SBTKAs with
275
longer operative times are protective against VTE. This might be due to more rigorous VTE
276
prophylaxis measures undertaken for patients who had longer operative times.
TE D
M AN U
SC
270
Several previous studies have tried to analyze predictors or risk factors of transfusion in
278
total hip and knee arthroplasty with varying results. While some have found no correlation
279
between obesity and blood loss[51-53], others have found increased blood loss with elevated
280
BMI[54]. Although SBTKA is associated with increased blood loss compared to unilateral
281
procedures, our study showed that in the subgroup of patients with BMI > 30 Kg/m2, SBTKA
282
was associated with even a higher rate of bleeding. Black race, Asian origin and race other than
283
white, black or Asian were also subgroups that showed increased likelihood of bleeding when
284
undergoing SBTKA compared to a unilateral procedure. It has been shown that increased age is
285
associated with increased blood loss and transfusion in patients undergoing TKA [53, 55] or
286
THA [56, 57]. However the effect of age and bilaterality of the procedure on bleeding has not
AC C
EP
277
ACCEPTED MANUSCRIPT 14 been analyzed. Although SBTKA was associated with a significantly higher rate of bleeding
288
across all age groups compared to unilateral procedures, patients older than 85 years were at a
289
particularly increased risk of this complication when undergoing SBTKA compared to unilateral
290
TKA (OR 5.64 95% CI: 2.59 - 12.29). To deter its effect on the outcome, preoperative Hct was
291
one of the confounders controlled for in the subgroup analysis. These subgroups of patents with
292
increased risk of complications should be noted when deciding between unilateral or bilateral
293
TKA.
SC
RI PT
287
There were several unusual findings in the subgroup stratification that could not be
295
explained, although they were statistically significant after adjusting for confounders. Patients
296
with bleeding disorders and INR > 1.2 were at a lower risk of bleeding when undergoing
297
SBTKA compared to patients with no bleeding disorders and an INR ≤ 1.2. This might be due to
298
more rigorous homeostasis in these subgroups or the use of Tranexamic acid which the NSQIP
299
does not record.
300
An important limitation of this study is that the ACS-NSQIP is unable to capture staged
301
procedures or the time between them and does not include outcomes beyond 30 days. Some
302
cases of unilateral TKA in this study may have been part of a staged procedure, thus skewing the
303
results. Other limitations involving shortfalls of the database include an inability to gather data
304
on surgeon experience, hospital volume, VTE prophylaxis, use of drains, re-infusion systems,
305
tourniquet, and tranexamic acid. It is also not known whether VTE events were symptomatic or
306
diagnosed on routine ultrasounds. Functional outcomes and cost are also not recorded.
307
Furthermore, by using the NSQIP database or any other population based database selection bias
308
cannot be eliminated. This is depicted by the patient demographics (Table 1), that shows patients
309
undergoing SBTKA are healthier with less morbidities.
AC C
EP
TE D
M AN U
294
ACCEPTED MANUSCRIPT 15 310 Conclusion
312
SBTKA confers an increased risk of postoperative VTE and bleeding at 30 days, as well as an
313
increased risk of composite morbidity with no increase in mortality. Particular patient
314
characteristics may confer an increased risk for these complications. As the debate regarding the
315
risks and benefits of performing a SBTKA versus a unilateral or staged bilateral TKA continues,
316
research must focus on identifying individual patient risk factors for various complications, as
317
well as tailoring specific intraoperative practices to reduce the risk.
SC
RI PT
311
319
M AN U
318 References
320
EP
TE D
1. Lindberg-Larsen M, Jorgensen CC, Husted H, Kehlet H. Early morbidity after simultaneous and staged bilateral total knee arthroplasty. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 23(3): 831, 2015 2. Bohm ER, Molodianovitsh K, Dragan A, Zhu N, Webster G, Masri B, Schemitsch E, Dunbar M. Outcomes of unilateral and bilateral total knee arthroplasty in 238,373 patients. Acta orthopaedica 87 Suppl 1: 24, 2016 3. Bolognesi MP, Watters TS, Attarian DE, Wellman SS, Setoguchi S. Simultaneous vs staged bilateral total knee arthroplasty among Medicare beneficiaries, 2000-2009. The Journal of arthroplasty 28(8 Suppl): 87, 2013 4. Odum SM, Springer BD. In-Hospital Complication Rates and Associated Factors After Simultaneous Bilateral Versus Unilateral Total Knee Arthroplasty. The Journal of bone and joint surgery American volume 96(13): 1058, 2014 5. Odum SM, Troyer JL, Kelly MP, Dedini RD, Bozic KJ. A cost-utility analysis comparing the cost-effectiveness of simultaneous and staged bilateral total knee arthroplasty. The Journal of bone and joint surgery American volume 95(16): 1441, 2013 6. Lin AC, Chao E, Yang CM, Wen HC, Ma HL, Lu TC. Costs of staged versus simultaneous bilateral total knee arthroplasty: a population-based study of the Taiwanese National Health Insurance Database. Journal of orthopaedic surgery and research 9: 59, 2014 7. Fu D, Li G, Chen K, Zeng H, Zhang X, Cai Z. Comparison of clinical outcome between simultaneous-bilateral and staged-bilateral total knee arthroplasty: a systematic review of retrospective studies. The Journal of arthroplasty 28(7): 1141, 2013 8. Oakes DA, Hanssen AD. Bilateral total knee replacement using the same anesthetic is not justified by assessment of the risks. Clinical orthopaedics and related research (428): 87, 2004
AC C
321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343
ACCEPTED MANUSCRIPT 16
EP
TE D
M AN U
SC
RI PT
9. Restrepo C, Parvizi J, Dietrich T, Einhorn TA. Safety of simultaneous bilateral total knee arthroplasty. A meta-analysis. The Journal of bone and joint surgery American volume 89(6): 1220, 2007 10. Hart A, Antoniou J, Brin YS, Huk OL, Zukor DJ, Bergeron SG. Simultaneous Bilateral Versus Unilateral Total Knee Arthroplasty: A Comparison of 30-Day Readmission Rates and Major Complications. The Journal of arthroplasty 31(1): 31, 2016 11. Suleiman LI, Edelstein AI, Thompson RM, Alvi HM, Kwasny MJ, Manning DW. Perioperative Outcomes Following Unilateral Versus Bilateral Total Knee Arthroplasty. The Journal of arthroplasty 30(11): 1927, 2015 12. Soudry M, Binazzi R, Insall JN, Nordstrom TJ, Pellicci PM, Goulet JA. Successive bilateral total knee replacement. The Journal of bone and joint surgery American volume 67(4): 573, 1985 13. Ritter MA, Meding JB. Bilateral simultaneous total knee arthroplasty. The Journal of arthroplasty 2(3): 185, 1987 14. Morrey BF, Adams RA, Ilstrup DM, Bryan RS. Complications and mortality associated with bilateral or unilateral total knee arthroplasty. The Journal of bone and joint surgery American volume 69(4): 484, 1987 15. Kim YH, Choi YW, Kim JS. Simultaneous bilateral sequential total knee replacement is as safe as unilateral total knee replacement. The Journal of bone and joint surgery British volume 91(1): 64, 2009 16. Hall BL, Hamilton BH, Richards K, Bilimoria KY, Cohen ME, Ko CY. Does surgical quality improve in the American College of Surgeons National Surgical Quality Improvement Program: an evaluation of all participating hospitals. Ann Surg 250(3): 363, 2009 17. Surgeons ACo. American College of Surgeons National Surgical Quality Improvement Program. User guide for the 2015 participant use data file. In. 2015 18. WHO Global Database on Body Mass Index (BMI): an interactive surveillance tool for monitoring nutrition transition. Public Health Nutrition 9(5): 658, 2006 19. Organization WH. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. In: Vitamin and Mineral Nutrition Information System (VMNIS). Geneva. 2011 20. Shao Y, Zhang C, Charron KD, Macdonald SJ, McCalden RW, Bourne RB. The fate of the remaining knee(s) or hip(s) in osteoarthritic patients undergoing a primary TKA or THA. The Journal of arthroplasty 28(10): 1842, 2013 21. Memtsoudis SG, Ma Y, Gonzalez Della Valle A, Mazumdar M, Gaber-Baylis LK, MacKenzie CR, Sculco TP. Perioperative outcomes after unilateral and bilateral total knee arthroplasty. Anesthesiology 111(6): 1206, 2009 22. Reuben JD, Meyers SJ, Cox DD, Elliott M, Watson M, Shim SD. Cost comparison between bilateral simultaneous, staged, and unilateral total joint arthroplasty. The Journal of arthroplasty 13(2): 172, 1998 23. Poultsides LA, Memtsoudis SG, Vasilakakos T, Wanivenhaus F, Do HT, Finerty E, Alexiades M, Sculco TP. Infection following simultaneous bilateral total knee arthroplasty. The Journal of arthroplasty 28(8 Suppl): 92, 2013 24. Courtney PM, Melnic CM, Alosh H, Shah RP, Nelson CL, Israelite CL. Is bilateral total knee arthroplasty staged at a one-week interval safe? A matched case control study. The Journal of arthroplasty 29(10): 1946, 2014 25. Meehan JP, Danielsen B, Tancredi DJ, Kim S, Jamali AA, White RH. A population-based comparison of the incidence of adverse outcomes after simultaneous-bilateral and staged-
AC C
344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388
ACCEPTED MANUSCRIPT 17
EP
TE D
M AN U
SC
RI PT
bilateral total knee arthroplasty. The Journal of bone and joint surgery American volume 93(23): 2203, 2011 26. Abram SG, Nicol F, Spencer SJ. Patient reported outcomes in three hundred and twenty eight bilateral total knee replacement cases (simultaneous versus staged arthroplasty) using the Oxford Knee Score. International orthopaedics 40(10): 2055, 2016 27. Memtsoudis SG, Hargett M, Russell LA, Parvizi J, Cats-Baril WL, Stundner O, Sculco TP, Consensus Conference on Bilateral Total Knee Arthroplasty G. Consensus statement from the consensus conference on bilateral total knee arthroplasty group. Clinical orthopaedics and related research 471(8): 2649, 2013 28. Memtsoudis SG, Ma Y, Chiu YL, Poultsides L, Gonzalez Della Valle A, Mazumdar M. Bilateral total knee arthroplasty: risk factors for major morbidity and mortality. Anesth Analg 113(4): 784, 2011 29. Ritter MA, Harty LD, Davis KE, Meding JB, Berend M. Simultaneous bilateral, staged bilateral, and unilateral total knee arthroplasty. A survival analysis. The Journal of bone and joint surgery American volume 85-A(8): 1532, 2003 30. Bullock DP, Sporer SM, Shirreffs TG, Jr. Comparison of simultaneous bilateral with unilateral total knee arthroplasty in terms of perioperative complications. The Journal of bone and joint surgery American volume 85-A(10): 1981, 2003 31. Mangaleshkar SR, Prasad PS, Chugh S, Thomas AP. Staged bilateral total knee replacement-a safer approach in older patients. The Knee 8(3): 207, 2001 32. Ritter MA, Harty LD. Debate: simultaneous bilateral knee replacements: the outcomes justify its use. Clinical orthopaedics and related research (428): 84, 2004 33. Fabi DW, Mohan V, Goldstein WM, Dunn JH, Murphy BP. Unilateral vs bilateral total knee arthroplasty risk factors increasing morbidity. The Journal of arthroplasty 26(5): 668, 2011 34. Peskun C, Mayne I, Malempati H, Kosashvili Y, Gross A, Backstein D. Cardiovascular disease predicts complications following bilateral total knee arthroplasty under a single anesthetic. The Knee 19(5): 580, 2012 35. Parvizi J, Sullivan TA, Trousdale RT, Lewallen DG. Thirty-day mortality after total knee arthroplasty. The Journal of bone and joint surgery American volume 83-A(8): 1157, 2001 36. Leonard L, Williamson DM, Ivory JP, Jennison C. An evaluation of the safety and efficacy of simultaneous bilateral total knee arthroplasty. The Journal of arthroplasty 18(8): 972, 2003 37. Lane GJ, Hozack WJ, Shah S, Rothman RH, Booth RE, Jr., Eng K, Smith P. Simultaneous bilateral versus unilateral total knee arthroplasty. Outcomes analysis. Clinical orthopaedics and related research (345): 106, 1997 38. Hussain N, Chien T, Hussain F, Bookwala A, Simunovic N, Shetty V, Bhandari M. Simultaneous versus staged bilateral total knee arthroplasty: a meta-analysis evaluating mortality, peri-operative complications and infection rates. HSS journal : the musculoskeletal journal of Hospital for Special Surgery 9(1): 50, 2013 39. Jhurani A, Shetty GM, Gupta V, Saxena P, Singh N. Effect of Closed Suction Drain on Blood Loss and Transfusion Rates in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Study. Knee surgery & related research 28(3): 201, 2016 40. Watanabe T, Muneta T, Yagishita K, Hara K, Koga H, Sekiya I. Closed Suction Drainage Is Not Necessary for Total Knee Arthroplasty: A Prospective Study on Simultaneous Bilateral Surgeries of a Mean Follow-Up of 5.5 Years. The Journal of arthroplasty 31(3): 641, 2016
AC C
389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432
ACCEPTED MANUSCRIPT 18
EP
TE D
M AN U
SC
RI PT
41. Jiang X, Ma XL, Ma JX. Efficiency and Safety of Intravenous Tranexamic Acid in Simultaneous Bilateral Total Knee Arthroplasty: A Systematic Review and Meta-analysis. Orthopaedic surgery 8(3): 285, 2016 42. Barrett J, Baron JA, Losina E, Wright J, Mahomed NN, Katz JN. Bilateral total knee replacement: staging and pulmonary embolism. The Journal of bone and joint surgery American volume 88(10): 2146, 2006 43. Memtsoudis SG, Besculides MC, Reid S, Gaber-Baylis LK, Gonzalez Della Valle A. Trends in bilateral total knee arthroplasties: 153,259 discharges between 1990 and 2004. Clinical orthopaedics and related research 467(6): 1568, 2009 44. Sheth DS, Cafri G, Paxton EW, Namba RS. Bilateral Simultaneous vs Staged Total Knee Arthroplasty: A Comparison of Complications and Mortality. The Journal of arthroplasty 31(9 Suppl): 212, 2016 45. Sliva CD, Callaghan JJ, Goetz DD, Taylor SG. Staggered bilateral total knee arthroplasty performed four to seven days apart during a single hospitalization. The Journal of bone and joint surgery American volume 87(3): 508, 2005 46. Liu J, Elkassabany N, Poultsides L, Nelson CL, Memtsoudis SG. Staging Bilateral Total Knee Arthroplasty During the Same Hospitalization: The Impact of Timing. The Journal of arthroplasty 30(7): 1172, 2015 47. Stundner O, Chiu YL, Sun X, Mazumdar M, Fleischut P, Poultsides L, Gerner P, Fritsch G, Memtsoudis SG. Comparative perioperative outcomes associated with neuraxial versus general anesthesia for simultaneous bilateral total knee arthroplasty. Regional anesthesia and pain medicine 37(6): 638, 2012 48. Heit JA, Beckman MG, Bockenstedt PL, Grant AM, Key NS, Kulkarni R, Manco-Johnson MJ, Moll S, Ortel TL, Philipp CS. Comparison of characteristics from White- and BlackAmericans with venous thromboembolism: a cross-sectional study. Am J Hematol 85(7): 467, 2010 49. White RH, Keenan CR. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res 123 Suppl 4: S11, 2009 50. Kim JY, Khavanin N, Rambachan A, McCarthy RJ, Mlodinow AS, De Oliveria GS, Jr., Stock MC, Gust MJ, Mahvi DM. Surgical duration and risk of venous thromboembolism. JAMA Surg 150(2): 110, 2015 51. Hrnack SA, Skeen N, Xu T, Rosenstein AD. Correlation of body mass index and blood loss during total knee and total hip arthroplasty. Am J Orthop (Belle Mead NJ) 41(10): 467, 2012 52. Park JH, Rasouli MR, Mortazavi SM, Tokarski AT, Maltenfort MG, Parvizi J. Predictors of perioperative blood loss in total joint arthroplasty. The Journal of bone and joint surgery American volume 95(19): 1777, 2013 53. Bong MR, Patel V, Chang E, Issack PS, Hebert R, Di Cesare PE. Risks associated with blood transfusion after total knee arthroplasty. The Journal of arthroplasty 19(3): 281, 2004 54. Frisch N, Wessell NM, Charters M, Peterson E, Cann B, Greenstein A, Silverton CD. Effect of Body Mass Index on Blood Transfusion in Total Hip and Knee Arthroplasty. Orthopedics 39(5): e844, 2016 55. Guerin S, Collins C, Kapoor H, McClean I, Collins D. Blood transfusion requirement prediction in patients undergoing primary total hip and knee arthroplasty. Transfus Med 17(1): 37, 2007
AC C
433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476
ACCEPTED MANUSCRIPT 19 56. Browne JA, Adib F, Brown TE, Novicoff WM. Transfusion rates are increasing following total hip arthroplasty: risk factors and outcomes. The Journal of arthroplasty 28(8 Suppl): 34, 2013 57. Walsh M, Preston C, Bong M, Patel V, Di Cesare PE. Relative risk factors for requirement of blood transfusion after total hip arthroplasty. The Journal of arthroplasty 22(8): 1162, 2007
RI PT
477 478 479 480 481 482
AC C
EP
TE D
M AN U
SC
483
ACCEPTED MANUSCRIPT
Appendix 1. Confounders Return OR
Composite Morbidity
Intubation [Unplanned Intubation + Intubation >48]
X X
X X X X X X X X X X
X X
X X X X X X X X X X X X X X X
X X
X X X X X X
X X
X X X
X X X X X X X X X X X
X X X X X X X X
X X X
X X
X X X
X X
X X X X X X X X X X X X X X X
X
Wound Complications
Deep Infection
Sepsis
X X
X X
X X
X X
X
X X X X X X
X X X X X X X
X X X X X X X
X X X X X X X
X X X X
X X X X
X X X X
X X X X
X X
X X
X X
X X X X X X X X X
X X X X X X X X X
X X X X X X X X X
X
X
X
X
X
X X X X X X X
X X X
X X
X
X
X X
Progressive Renal Insuffieciency
X X
SC
X X X X X X X X
M AN U
X X X
TE D
X X X
X X X X X X X
EP
X X X
UTI
RI PT
Thromboe mbolism
AC C
Age Gender Race Type of Anesthesia ASA Class Mean Total Operation Time min Days from admission to operation Transfusions in 72 h before surgery CHF w/in 30days Tobacco use in past year History of severe COPD Acute renal failure Currently on dialysis Bleeding disorder Weight loss > 10% in previous 6 months BMI Diabetic on oral drugs or insulin Hypertension requiring meds Steroid use for chronic condition WBC count Platelet count INR BUN Creatinine Serum albumin Dyspnea Functional health status Prior to Surgery Ascites Hematocrit PTT
Bleeding
X X
X X X
X X X X
X
ACCEPTED MANUSCRIPT
58,188 (37.6%) 96,724 (62.4%)
56310 (37.42%) 94168 (62.58%)
121582 (88.3%) 11,330 (8.2%) 3,368 (2.4%) 1,338 (1%)
117858 (88.34%) 11027 (8.27%) 3229 (2.42%) 1301 (0.98%)
151563 (98.4%) 2,421 (1.6%) 88 (0.1%) 32.00 ± 7.05 377 (0.2%) 15,288 (9.9%) 42,246 (27.3%) 43,943 (28.4%) 29,191 (18.9%) 23,513 (15.2%) 13,198 (8.5%) 27,854 (18%) 102220 (65.9%) 5,261 (3.4%)
p-value <0.0001 <0.0001
<0.0001
3724 (88.6%) 303 (7.21%) 139 (3.31%) 37 (0.88%)
0.0003
78345 (52.08%) 72099 (47.92%) 92.38 ± 36.39 125476 (83.33%) 21969 (14.59%) 3125 (2.08%)
2654 (59.88%) 1778 (40.12%) 148.97 ± 54.70 1449 (32.63%) 1943 (43.75%) 1049 (23.62%)
<0.0001
147206 (98.35%) 2377 (1.59%) 87 (0.06%) 32.99 ± 7.05 364 (0.24%) 14902 (9.93%) 41041 (27.34%) 42665 (28.42%) 28290 (18.84%) 22868 (15.23%) 12844 (8.53%) 27187 (18.05%) 99503 (66.08%) 5124 (3.4%)
4357 (98.98%) 44 (1%) 1 (0.02%) 33.13 ± 7.07 13 (0.29%) 386 (8.72%) 1205 (27.21%) 1278 (28.86%) 901 (20.35%) 645 (14.57%) 354 (7.97%) 667 (15.02%) 2717 (61.18%) 137 (3.08%)
0.0052
M AN U
SC
1878 (42.35%) 2556 (57.65%)
TE D
80,999 (52.3%) 73,877 (47.7%) 94.00 ± 38.22 126925 (81.9%) 23,912 (15.4%) 4,174 (2.7%)
Bilateral TKA n=4,441 (2.86%) 64.09 ± 8.81 2264 (50.98%) 2149 (48.39%) 28 (0.63%)
RI PT
Unilateral TKA n=150581 (97.14%) 66.79 ± 9.76 60,806 (40.38%) 86589 (57.5%) 3186 (2.12%)
EP
Age (years) <65 65-85 >85 Gender Male Female Race / Ethnicity White Black Asian Other ASA Class I - II III - V Mean Total Operation Time(min) <120 min 120-179 min ≥180 min Functional status prior to surgery Independent Partially dependent Dependent BMI (Kg/m2)a <18.5 18.5-24.9 25-29.9 30-34.9 35-39.9 ≥40 Smoker Diabetes on oral drugs or insulin Hypertension requiring medication Steroid use for chronic condition
All TKAs (n=155022) 66.71 ± 9.74 63,070 (40.7%) 88,738 (57.2%) 3,214 (2.1%)
AC C
Table 1. Patient Characteristics
<0.0001 <0.0001
0.2075 0.02
0.1888 <0.0001 <0.0001 0.2488
ACCEPTED MANUSCRIPT
102 (2.3%) 200 (4.5%) 4 (0.09%)
<0.0001 <0.0001 0.0297
2742 (61.76%) 1311 (29.53%) 387 (8.72%) 0 (0%) 5 (0.11%) 0.88 ± 0.32 3764 (89.83%) 426 (10.17%) 6 (0.14%) 84 (1.89%) 4 (0.09%) 6.94 ± 1.96 4066 (96.56%) 145 (3.44%) 246.79 ± 66.22 169 (4.02%) 4036 (95.98%) 1.01 ± 0.24 2878 (97.99%) 59 (2.01%) 139.61 ± 2.71 256 (6.18%) 3884 (93.82%) 41.03 ± 4.13 3628 (85.85%) 575 (13.61%) 23 (0.54%) 29.06 ± 4.67
<0.0001
AC C
EP
TE D
M AN U
SC
RI PT
Severe COPD 5,510 (3.6%) 5408 (3.59%) Dyspnea 9,827 (6.3%) 9627 (6.39%) CHF (within 30 days) 389 (0.3%) 385 (0.26%) Anesthesia technique General 78,528 (50.7%) 75786 (50.34%) Spinal/Epidural 62,053 (40%) 60742 40.34%) Others 14,418 (9.3%) 14031 (9.32%) Acute renal failure 46 (0.00%) 46 (0.03%) Currently on dialysis 234 (0.2%) 229 (0.15%) Pre-operative serum creatinine (mg/dL) 0.92 ± 0.41 0.92 ± 0.41 <1.2 (mg/dL) 127435 (87.7%) 123671 (87.76%) ≥1.2 (mg/dL) 17,681 (12.2%) 17255 (12.24%) >10% loss body weight in last 6 months 205 (0.1%) 199 (0.13%) Bleeding disorders 3,717 (2.4%) 3633 (2.41%) Transfusion PRBCs in 72 hours before surgery 71 (0.00%) 67 (0.04%) Pre-operative WBC (103 cells/µL) 7.05 ± 2.17 7.06 ± 2.17 ≤11 (103 cells/µL) 141444 (96.4%) 137378 (96.37%) 3 >11 (10 cells/µL) 5,320 (3.6%) 5175 (3.63%) Pre-operative platelet count (per µL) 244.42 ± 66.65 244.34 ± 66.66 ≤150 (per µL) 7,222 (4.9%) 7053 (4.95%) >150 (per µL) 139514 (95.1%) 135478 (95.05%) Pre-operative INR 1.03 ± 0.26 1.03 ± 0.26 ≤1.2 99,362 (96.9%) 96484 (96.92%) >1.2 3,129 (3.1%) 3070 (3.08%) Pre-operative serum sodium (mEq/L) 139.48 ± 2.78 139.47 ± 2.78 ≤135 (mEq/L) 10,267 (7.1%) 10011 (7.18%) >135 (mEq/L) 133381 (92.9%) 129497 (92.82%) b Hematocrit (%) 40.73 ± 4.06 40.72 ± 4.06 no anemia 125154 (84.6%) 121526 (84.55%) mild anemia 22,056 (14.9%) 21481 (14.95%) moderate-severe anemia 749 (0.5%) 726 (0.51%) PTT 29.16 ± 4.63 29.16 ±4.63 a BMI classification was adapted from the World Health organization (WHO) global database16 b Anemia was defined using the WHO sex based criteria17
0.6437 0.5041 <0.0001 <0.0001 0.9575 0.0252 0.1464 0.0003 0.5226 0.0188 0.006 0.0007 0.0008 0.0026 0.0146 <0.0001 0.0529
0.3167
ACCEPTED MANUSCRIPT
Table 2. Complications
Unilateral TKA (n=150581) N %
SBTKA
Unadjusted
Adjusted
(n=4441) N %
OR (95% CI)
p-value 0.4956
OR (95% CI)
p-value
<0.0001 <0.0001 0.001 <0.0001
3.95 (3.65-4.27) 1.97 (1.64-2.37) 1.18 (0.92-1.51) 1.48 (1.30-1.67)
<0.0001 <0.0001 0.1929 <0.0001
0.11
6
0.14
1.23 (0.55-2.79)
11448 2185 1731 6980
7.6 1.45 1.15 4.64
1128 121 75 305
25.4 2.72 1.69 6.87
4.14 (3.86-4.44) 1.90 (1.58-2.29) 1.48 (1.17-1.87) 1.52 (1.35-1.71)
Cardiac complicationsb Pneumonia Intubationc Urinary tract Infection Acute Renal Failure Progressive Renal Insufficiency
408 530 247 1369 94 180
0.27 0.35 0.16 0.91 0.06 0.12
13 18 14 68 2 12
0.29 0.41 0.32 1.53 0.05 0.27
1.08 (0.62-1.88) 1.15 (0.72-1.85) 1.93 (1.12-3.30) 1.70 (1.33-2.17) 0.72 (0.18-2.93) 2.26 (1.26-4.06)
0.7834 0.555 0.0238 <0.0001 1 0.0049
1.76 (0.99-3.15) 1.70 (1.31-2.20)
0.0556 <0.0001
2.71 (1.50-4.88)
0.0009
CVA Wound complicationsd Superficial Surgical Site infection
127 1443 826
0.08 0.96 0.55
5 49 24
0.11 1.1 0.54
1.34 (0.55-3.27) 1.15 (0.87-1.54) 0.99 (0.66-1.48)
0.4333 0.3109 0.9424
0.93 (0.69-1.25)
0.6264
0.19
9
0.2
1.05 (0.54-2.04)
0.8882
0.28
20
0.45
1.60 (1.02-2.51)
0.039
1.10 (0.68-1.77)
0.6921
Wound dehiscence
291
Deep infection
425
e
SC
M AN U
TE D
Bleeding Thromboembolism Return to OR Composite morbiditya
RI PT
165
Mortality
AC C
EP
Sepsis 403 0.27 20 0.45 1.69 (1.08-2.64) 0.0214 1.30 (0.80-2.10) 0.2905 Composite morbidity includes thromboembolism, cardiac complications, pneumonia, intubation >48 hrs, unplanned intubation, urinart tract infection, acute renal failure, progressive renal insufficiency, CVA, superficial surgical Site infection, wound dehiscence, deep infection and sepsis b Cardiac Complications include myocardial infarction and/or cardiac arrest requiring CPR c Intubation includes unplanned intubation and/or intubation more than 48 hours d Wound complications include Superficial surgical site infection, wound dehiscence and deep surgical site infection e Sepsis includes sepsis and septic shock a
ACCEPTED MANUSCRIPT
P Value
Adjusted OR (95% CI)
P Value
% 2.72
1.90 (1.58-2.29)
<0.0001
1.97 (1.64-2.37)
<0.0001
48 73
2.56 2.85
1.87 (1.39-2.51) 1.94 (1.53- 2.46)
< 0.0001 < 0.0001
1.99 (1.48- 2.69) 2.04 (1.60- 2.59)
< 0.0001 < 0.0001
1.28 1.55 1.95
61 58 2
2.69 2.7 7.14
2.13 (1.63- 2.77) 1.76 (1.35- 2.30) 3.88 (0.90- 16.69)
< 0.0001 < 0.0001 0.106
2.15 (1.65- 2.80) 1.81 (1.39- 2.36) 4.25 (0.98-18.38)
< 0.0001 < 0.0001 0.0528
1875 248 38 24
1.41 2 1.04 1.63
99 17 5 0
2.52 5.2 3.52 0
1.81 (1.47- 2.22) 2.69 (1.63- 4.46) 3.48 (1.35- 8.98) N/A
< 0.0001 < 0.0001 0.0208 1
1.86 (1.51- 2.28) 3.10 (1.85- 5.22) 3.48 (1.35- 8.98) N/A
< 0.0001 < 0.0001 0.0099
3 169 591
0.82 1.13 1.44
30-34.9 (n=44407) 35-39.9 (n=29191)
657 444
1.52 1.57
≥40 (n=23513)
321
No (n=127168) Yes (n=27854) Smoking No (n=141824)
Diabetes
Yes (n=13198) ASA class
n 121
781 1404
1.39 1.49
781 1342 62
SC
% 1.45
M AN U
n 2185
0 9 31
0 2.33 2.57
N/A 2.08 (1.06- 4.10) 1.81 (1.25- 2.61)
1 0.0473 0.0013
N/A 1.73 (0.84- 3.57) 1.96 (1.36- 2.83)
0.138 0.0003
EP
Age <65 (n=63070) 65-85 (n=88738) >85 (n=3214) Race White (n=136950) Black (n=12757) Asian (n=3803) Other (n=1512) BMI <18.5 (n=377) 18.5-24.9 (n=15288) 25-29.9 (n=42246)
SBTKA
42 23
3.25 2.55
2.17 (1.58- 2.98) 1.64 (1.08- 2.51)
< 0.0001 0.0206
2.75 (1.96- 3.85) 1.70 (1.11- 2.60)
< 0.0001 0.0148
1.4
16
2.48
1.79 (1.08- 2.97)
0.0232
1.70 (1.02- 2.85)
0.0425
1799 386
1.46 1.42
103 18
2.73 2.78
1.90 (1.55- 2.32) 1.93 (1.19- 3.11)
< 0.0001 0.0063
1.97 (1.61- 2.40) 2.01 (1.25- 3.25)
< 0.0001 0.0043
2013
1.46
112
2.74
1.90 (1.57- 2.30)
< 0.0001
1.97 (1.63- 2.39)
< 0.0001
172
1.34
9
2.54
1.92 (0.98- 3.79)
0.0623
1.98 (1.00- 3.90)
0.0496
AC C
Thromboembolism (All) Gender Male (n=58188) Female (n=96834)
Unilateral TKA
RI PT
Unadjusted OR (95% CI)
TE D
Table 3. Stratification of Patients with Thromboembolism
ACCEPTED MANUSCRIPT
CHF (within 30 days) No (n=154633) Yes (n=389) Dyspnea No (n=145195) Yes (n=9827) Transfusion before surgery No (n=154951) Yes (n=71) Preop INR ≤1.2 (n=151893) >1.2 (n=3129)
< 0.0001 0.0005
2.13 (1.68- 2.70) 1.79 (1.33- 2.42)
< 0.0001 0.0001
1106 879
1.46 1.45
73 31
2.66 2.36
1.85 (1.45- 2.35) 1.65 (1.15- 2.37)
< 0.0001 0.0063
1.91 (1.50- 2.43) 1.73 (1.21- 2.49)
< 0.0001 0.003
200
1.43
17
4.39
3.18 (1.92- 5.27)
< 0.0001
3.70 (2.20- 6.19)
< 0.0001
2153 29
1.45 1.22
119 2
2.71 4.55
1.89 (1.57- 2.27) 3.86 (0.89- 16.69)
< 0.0001 0.1077
1.95 (1.62- 2.36) 3.88 (0.89- 16.89)
< 0.0001 0.0707
3
3.45
0
0
N/A
0.8501
N/A
2109 76
1.44 2.09
119 2
1833 307 45
1.46 1.4 1.44
48 47 26
2180 5
1.45 1.3
1998 187
1.42 1.94
RI PT
2.09 (1.65- 2.65) 1.70 (1.26- 2.29)
SC
Bleeding disorder No (n=151305) Yes (n=3717) Operative time <120 min (n=126936) 120-179 min (n=23912) ≥180 min (n=4174)
2.82 2.59
M AN U
Dependent (n=88)
75 46
2.73 2.38
1.93 (1.60- 2.33) 1.14 (0.28- 4.73)
< 0.0001 0.696
2.01 (1.66- 2.42) 1.13 (0.27- 4.68)
< 0.0001 0.8716
3.31 2.42 2.48
2.31 (1.73- 3.09) 1.75 (1.28- 2.39) 1.74 (1.07- 2.83)
< 0.0001 < 0.0001 0.0244
2.35 (1.76- 3.15) 1.86 (1.36- 2.54) 1.74 (1.07- 2.83)
< 0.0001 < 0.0001 0.0262
TE D
Others (n=14418) Functional health status Independent (n=152513) Partially dependent (n=2421)
1.37 1.54
2.73 0
1.74 (1.07- 2.83) N/A
< 0.0001 1
1.97 (1.64- 2.37) N/A
< 0.0001
114 7
2.69 3.5
1.92 (1.59- 2.33) 1.83 (0.85- 3.95)
< 0.0001 0.1189
1.98 (1.64- 2.40) 1.98 (0.92- 4.29)
< 0.0001 0.0819
121 0
EP
Type of anesthesia General (n=78551) Spinal/Epidural (n=62053)
1073 1112
AC C
I - II (n=81145) III - V (n=73877)
2185 0
1.45 0
121 0
2.73 0
1.90 (1.58- 2.29)
< 0.0001
1.97 (1.64- 2.37)
< 0.0001
2137 48
1.45 1.56
119 2
2.72 3.39
1.90 (1.58- 2.29) 2.21 (0.52- 9.31)
< 0.0001 0.2428
1.97 (1.64- 2.38) 2.29 (0.54- 9.67)
< 0.0001 0.2606
ACCEPTED MANUSCRIPT
Table 4. Stratification of Patients with Bleeding P Value
Adjusted OR (95% CI)
P Value
% 25.4
4.14 (3.86-4.44)
<0.0001
3.95 (3.65-4.27)
<0.0001
383 745
20.39 29.07
3.75 (3.34- 4.22) 4.51 (4.13- 4.93)
< 0.0001 < 0.0001
3.90 (3.42- 4.45) 3.98 (3.60- 4.39)
< 0.0001 < 0.0001
5.88 8.45 17.33
516 599 13
22.79 27.87 46.43
4.72 (4.26- 5.24) 4.19 (3.80- 4.61) 4.14 (1.96- 8.74)
< 0.0001 < 0.0001 < 0.0001
4.00 (3.56- 4.49) 3.89 (3.49- 4.33) 5.64 (2.59- 12.29)
< 0.0001 < 0.0001 < 0.0001
10015 1104 285 44
7.53 8.88 7.78 2.98
992 97 35 4
4.14 (3.84- 4.46) 4.33 (3.39- 5.53) 3.88 (2.60- 5.78) 3.94 (1.34- 11.61)
< 0.0001 < 0.0001 < 0.0001 0.0274
3.92 (3.60- 4.26) 4.15 (3.16- 5.44) 4.03 (2.59- 6.27) 5.15 (1.69- 15.72)
< 0.0001 < 0.0001 < 0.0001 0.004
53 1769 3577
14.56 11.87 8.72
30.77 31.35 27.39
2.61 (0.78- 8.77) 3.39 (2.72- 4.23) 3.95 (3.46- 4.50)
0.117 < 0.0001 < 0.0001
4.39 (1.22- 15.79) 3.37 (2.64- 4.30) 3.90 (3.36- 4.52)
0.0234 < 0.0001 < 0.0001
30-34.9 (n=44407) 35-39.9 (n=29191)
3029 1763
7.03 6.23
318 208
24.63 23.09
4.33 (3.79- 4.94) 4.52 (3.84- 5.31)
< 0.0001 < 0.0001
4.11 (3.54- 4.76) 4.12 (3.44- 4.95)
< 0.0001 < 0.0001
≥40 (n=23513)
1257
5.5
147
22.79
5.08 (4.19- 6.15)
< 0.0001
4.13 (3.33- 5.13)
< 0.0001
No (n=149761) Yes (n=5261)
10980 468
7.55 9.13
1092 36
25.37 26.28
4.16 (3.88- 4.47) 3.55 (2.40- 5.25)
< 0.0001 < 0.0001
3.95 (3.64- 4.28) 3.93 (2.55- 6.08)
< 0.0001 < 0.0001
ASA class I - II (n=81145) III - V (n=73877)
5014 6434
6.39 8.92
653 475
24.52 26.72
4.76 (4.34- 5.22) 3.72 (3.34- 4.15)
< 0.0001 < 0.0001
4.18 (3.76- 4.64) 3.68 (3.26- 4.15)
< 0.0001 < 0.0001
Steroid Use
n 1128
3600 7848
6.36 8.32
3577 7319 552
25.21 29.66 24.65 10.81
TE D
EP
4 121 330
SC
% 7.6
M AN U
n 11448
AC C
Age <65 (n=63070) 65-85 (n=88738) >85 (n=3214) Race White (n=136950) Black (n=12757) Asian (n=3803) Other (n=1512) BMI <18.5 (n=377) 18.5-24.9 (n=15288) 25-29.9 (n=42246)
SBTKA
RI PT
Unadjusted OR (95% CI)
Bleeding (ALL) Gender Male (n=58188) Female (n=96834)
Unilateral TKA
ACCEPTED MANUSCRIPT
29.97 16.86
4.47 (4.10- 4.87) 2.97 (2.56- 3.45)
< 0.0001 < 0.0001
4.53 (4.11- 5.00) 2.71 (2.31- 3.19)
< 0.0001 < 0.0001
942
6.71
85
21.96
3.91 (3.05- 5.02)
< 0.0001
4.42 (3.39- 5.76)
< 0.0001
11014 434
7.5 11.95
1099 29
25.22 34.52
4.16 (3.88- 4.47) 3.89 (2.45- 6.16)
< 0.0001 < 0.0001
3.96 (3.66- 4.29) 3.38 (1.99- 5.76)
< 0.0001 < 0.0001
9125 1870 453
7.27 8.51 14.5
356 464 308
24.57 23.88 29.36
4.15 (3.68- 4.69) 3.37 (3.01- 3.78) 2.45 (2.08- 2.90)
< 0.0001 < 0.0001 < 0.0001
4.73 (4.17- 5.37) 3.94 (3.49- 4.45) 2.89 (2.42- 3.45)
< 0.0001 < 0.0001 < 0.0001
3351 8097
6.56 8.14
420 708
7287 3928 233
5.68 18.28 32.05
850 269 9
11423 25
7.59 37.31
11100 348
7.52 11.34
1124 4 1116 12
M AN U
SC
RI PT
822 221
24.36 26.06
4.59 (4.09- 5.15) 3.98 (3.64- 4.35)
< 0.0001 < 0.0001
3.92 (3.44- 4.46) 3.96 (3.59- 4.38)
< 0.0001 < 0.0001
22.13 46.62 39.13
4.72 (4.36- 5.11) 3.91 (3.30- 4.62) 1.36 (0.58- 3.20)
< 0.0001 < 0.0001 0.4745
4.10 (3.75- 4.48) 3.53 (2.95- 4.23) 1.37 (0.52-3.60)
< 0.0001 < 0.0001 0.5269
25.33 100
4.13 (3.85- 4.43) N/A
< 0.0001 0.0244
3.95 (3.65- 4.27)
< 0.0001
25.47 20.34
4.20 (3.91- 4.51) 2.00 (1.05- 3.80)
< 0.0001 0.0318
3.98 (3.68- 4.31) 2.51 (1.29- 4.87)
< 0.0001 0.0067
TE D
Hypertension No (n=52802) Yes (n=102220) Preop Hct no anemia (n=132204) mild anemia (n=22068) moderate-severe anemia (n=750) Transfusion before surgery No (n=154951) Yes (n=71) Preop INR ≤1.2 (n=151893) >1.2 (n=3129)
8.74 6.39
EP
Others (n=14418) Bleeding disorder No (n=151305) Yes (n=3717) Operative time <120 min (n=126936) 120-179 min (n=23912) ≥180 min (n=4174)
6627 3879
AC C
Type of anesthesia General (n=78551) Spinal/Epidural (n=62053)