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Peri‐operative administration of tranexamic acid in lower limb arthroplasty: a multicentre, prospective cohort study

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  • National Health Service
  • British Army

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In the UK , tranexamic acid is recommended for all surgical procedures where expected blood loss exceeds 500 ml. However, the optimal dose, route and timing of administration are not known. This study aimed to evaluate current practice of peri‐operative tranexamic acid administration. Patients undergoing primary total hip arthroplasty, total knee arthroplasty or unicompartmental knee arthroplasty during a 2‐week period were eligible for inclusion in this prospective study. The primary outcome was the proportion of patients receiving tranexamic acid in the peri‐operative period. Secondary outcomes included: dose, route and timing of tranexamic acid administration; prevalence of pre‐ and postoperative anaemia; estimated blood loss; and red blood cell transfusion rates. In total, we recruited 1701 patients from 56 NHS hospitals. Out of these, 1523 (89.5%) patients received tranexamic acid and of those, 1052 (69.1%) received a single dose of 1000 mg intravenously either pre‐ or intra‐operatively. Out of the 1701 patients, 571 (33.6%) and 1386 (81.5%) patients were anaemic (haemoglobin < 130 g.l⁻¹) in the pre‐ and postoperative period, respectively. Mean (SD ) estimated blood loss for all included patients was 792 (453) ml and 54 patients (3.1%) received a red blood cell transfusion postoperatively. The transfusion rate for patients with pre‐operative anaemia was 6.5%, compared with 1.5% in patients without anaemia. Current standard of care in the UK is to administer 1000 mg of tranexamic intravenously either pre‐ or intra‐operatively. Approximately one‐third of patients present for surgery with anaemia, although the overall red blood cell transfusion rate is low. These data provide useful comparators when assessing the efficacy of tranexamic acid and other patient blood management interventions in future studies.
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Original Article
Peri-operative administration of tranexamic acid in lower
limb arthroplasty: a multicentre, prospective cohort study
T. D. Lloyd,
1,2
G. Neal-Smith,
2
J. Fennelly,
2
H. Claireaux,
3
C. Bretherton,
2,4
A. J. Carr,
5
M. Murphy,
6,7
B. J. Kendrick,
8
A. J. R. Palmer,
9
and collaborators
a
1 National Institute for Health Research (NIHR) Academic Clinical Research Fellow, 4 Clinical Research Fellow, 5
Professor, 8 Honorary Senior Lecturer and Consultant, 9 NIHR Clinical Academic Lecturer, Nufeld Department of
Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
2 Trainee, 3 British Army General Duties Medical Ofcer, Oxford Surgical Collaborative for Audit and Research, Oxford,
UK
6 Professor, University of Oxford, Oxford, UK, 7 Consultant, NHS Blood and Transplant, Oxford, UK
Summary
In the UK, tranexamic acid is recommended for all surgical procedures where expected blood loss exceeds
500 ml. However, the optimal dose, route and timing of administration are not known. This study aimed to
evaluate current practice of peri-operative tranexamic acid administration. Patients undergoing primary total hip
arthroplasty, total knee arthroplasty or unicompartmental knee arthroplasty during a 2-week period were eligible
for inclusion in this prospective study. The primary outcome was the proportion of patients receiving tranexamic
acid in the peri-operative period. Secondary outcomes included: dose, route and timing of tranexamic acid
administration; prevalence of pre- and postoperative anaemia; estimated blood loss; and red blood cell
transfusion rates. In total, we recruited 1701 patients from 56 NHS hospitals. Out of these, 1523 (89.5%) patients
received tranexamic acid and of those, 1052 (69.1%) received a single dose of 1000 mg intravenously either pre-
or intra-operatively. Out of the 1701 patients, 571 (33.6%) and 1386 (81.5%) patients were anaemic (haemoglobin
<130 g.l
1
) in the pre- and postoperative period, respectively. Mean (SD) estimated blood loss for all included
patients was 792 (453) ml and 54 patients (3.1%) received a red blood cell transfusion postoperatively. The
transfusion rate for patients with pre-operative anaemia was 6.5%, compared with 1.5% in patients without
anaemia. Current standard of care in the UK is to administer 1000 mg of tranexamic intravenously either pre- or
intra-operatively. Approximately one-third of patients present for surgery with anaemia, although the overall red
blood cell transfusion rate is low. These data provide useful comparators when assessing the efcacy of
tranexamicacid and other patient blood managementinterventions in future studies.
.................................................................................................................................................................
Correspondence to: A. J. R. Palmer
Email: antony.palmer@ndorms.ox.ac.uk
Accepted: 12 March 2020
Keywords: anaemia; arthroplasty; blood loss; tranexamic acid; transfusion
a
For collaborators, see Appendix 1.
Twitter: @tomlloyd91; @GregNealSmith1; @harryclax; @BrethertonC; @MurphyProf; @AJRPalmer
Introduction
Primary hip and knee arthroplasty is often associated with
blood loss of more than a litre peri-operatively [1]. A
signicant proportion of patients may require an allogeneic
red blood cell transfusion, with rates ranging from 0 to 47%
[2]. In addition, both postoperative anaemia and red blood
cell transfusion are associated with increased risks of
cardiopulmonary morbidity, surgical site infection and
©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Associat ion of Anaesthetists 1
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and
distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modications or adaptations are made.
Anaesthesia 2020 doi:10.1111/anae.15056
mortality [3, 4]. Therefore, strategies to minimise intra-
operative blood loss and promote blood conservation are a
priority for improving patient outcomes [5].
Tranexamic acid is a synthetic lysine analogue that
inhibits plasminogen activation and promotes clot
stabilisation. In patients undergoing total hip or knee
arthroplasty, tranexamic acid has been shown to reduce
peri-operative blood loss and red blood cell transfusion
rates [6]. The National Institute for Health and Care
Excellence (NICE) guidelines recommend tranexamic acid
is administered to all patients undergoing a surgical
procedure with estimated blood loss greater than 500 ml
[7]. However, the guidelines did not provide a
recommendation on the dose, route or timing of
tranexamic administration due to the heterogeneity of
studies to date. In order to design an optimal clinical trial
an improved understanding of current practice is required,
particularly in terms of clinically relevant comparator
interventions and outcome measures.
The primary aim of this study was to evaluate current
practice of peri-operative tranexamic acid administration in
patients undergoing primary hip and knee arthroplasty in
the UK. Secondary aims were to identify the prevalence of
pre- and postoperative anaemia and to determine
estimated blood loss and postoperative red blood cell
transfusion rates.
Methods
This study is reported according to STROBE guidelines. A
multicentre, prospective, observational study was
conducted between 3 September 2018 and 17 September
2018. Collaborators from NHS Trusts within the UK were
recruited via the National Orthopaedic Trainee
Collaborative network and the British Orthopaedic
Trainees Association. Each collaborator registered the
audit locally with a clinical lead and the clinical audit and
effectiveness department at their respective institution.
Research Ethics Committee approval was not required as
per the Health Research Authority assessment tool.
Collaborators completed and returned locked Excel
spreadsheets (Microsoft Corp, NM, USA). No direct or
indirect patient identiable data were collected.
Patients undergoing elective primary total hip
arthroplasty, total knee arthroplasty or unicompartmental
knee arthroplasty within the study period were eligible for
inclusion. The following data were collected on tranexamic
administration: dose (mg); timing (pre-operative, intra-
operative, or postoperative); and route (oral, intravenous,
topical, intramuscular or combined). Additional data
included: body mass index ; weight; pre- and postoperative
haemoglobin concentration (Hb) and haematocrit (Hct);
and postoperative red blood cell transfusion requirements.
We calculated the estimated peri-operative blood loss for
each patient using the Gross equation (Equation 1). To
inform the estimated blood loss calculation, pre-operative
estimated blood volume was calculated using the
Lemmens-Bernstein-Brodsky equation [8].
Estimated blood loss ¼
estimated blood volume initial Hct final Hct
mean Hct

ð1Þ
Patients who were transfused intra-operatively or
received an autologous red blood cell transfusion before
the rst postoperative full blood count were not included in
calculations of estimated blood loss.
Pre-operative tranexamic acid administration included
doses given between admission and surgical incision.
Intra-operative administration included doses given
between surgical incision until the recorded end of the
procedure. Postoperative administration included doses
given from the recorded end of the procedure until patient
discharge. Pre-operative Hb and Hct values were recorded
from the most recent pre-operative laboratory full blood
count. Postoperative Hb and Hct values were recorded
from the rst laboratory full blood measured
postoperatively (and before any red blood cell blood
transfusion). Anaemia was dened as a haemoglobin
concentration less than 130 g.l
1
[9].
Regional variation in practice was explored by country
(England, Wales, Scotland, Northern Ireland), and England
was subdivided into Public Health England regions
(London, South East, South West, East of England, West
Midlands, East Midlands, North West, North East, and
Yorkshire and Humber).
We did not calculate a sample size for this analysis.
Differences between groups were assessed using an
unpaired, two-sided t-test for continuous variables and
Fishers exact test for categorical variables. All data
analyses were undertaken using STATA v14.2 (StataCorp,
TX, USA).
Results
Over the study period, data from 1714 patients
undergoing primary hip or knee arthroplasty were
included from 56 NHS hospitals in the UK (Fig. 1).
Thirteen patients were not included due to incomplete
data. Three were not included in the blood loss
calculations due to intra-operative transfusion (n =2) and
autologous transfusion (n =1) (Fig. 2).
2©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists
Anaesthesia 2020 Lloyd et al. | Peri-operative tranexamic acid in orthopaedic surgery
Out of the 1701 patients included in the nal analysis,
797 (46.9%) underwent total hip arthroplasty, 830 (48.9%)
total knee arthroplasty and 74 (4.4%) unicompartmental
knee arthroplasty. Mean (SD) weight of included patients
was 82.7 (18.3) kg and mean (SD) BMI was 30.2 (5.7) kg.m
2
.
In this study, 1523 out of 1701 (89.5%) received tranexamic
acid peri-operatively, with a similar proportion across all
three operations (Table 1). Mean (SD) estimated blood loss
for patients receiving tranexamic acid was 880.8 (458.6) ml
compared with 782.2 (450.8) ml for patients who did not
receive tranexamic acid (p =0.007).
The most commonly used tranexamic acid dosing
regimen was a single dose of 1000 mg administered
intravenously either pre-operatively [n =547 (36%)] or
intra-operatively [n =505 (33%)] (Fig. 3). Other routes
and timing of administration are displayed in Tables 1
Figure 1 Map of participating centres
Figure 2 Flow diagram of recruitment and analysis
©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Associat ion of Anaesthetists 3
Lloyd et al. | Peri-operative tranexamic acid in orthopaedic surgery Anaesthesia 2020
and 2. A total of 1231 (72%) patients received a single
dose of tranexamic acid compared with 292 (17%) who
received multiple doses (Table 2). The most frequently
administered single dose was 1000 mg [n =1310
(86.1%)] (Fig. 3). Mean (SD) total cumulative dose
administered was 1112 (600.5) mg.
In total, 517 out of 1701 (33.6%) patients presented
with pre-operative anaemia and 1386 (81.5%) were anaemic
postoperatively (Table 3). Data on estimated blood loss and
transfusion rates for the overall cohort and according to
operation type are in Table 3. The number of patients with
an estimated blood loss of greater than 500 ml was 1252
(73.7%). Out of these, 1110 (88.7%) received tranexamic
acid. The transfusion rate for patients with pre-operative
anaemia was 37/571 (6.5%) compared with 17/1130 (1.5%)
in patients without anaemia (p <0.0001). Two patients
required intra-operative transfusions and both were
anaemic pre-operatively (Hb 109 g.l
1
and 107 g.l
1
).
There was regional variation in practice with the lowest
recorded rate of pre-operative anaemia in north-east
England (22.0%) and highest in the Yorkshire and Humber
Table 1 Routes of tranexamic acid administration in all patients and those undergoing total hip arthroplasty, total knee
arthroplasty and unicompartmental knee arthroplasty. Values are number (proportion).
Dose Route
All
n=1701
Total hip
arthroplasty
n=797
Total knee
arthroplasty
n=830
Unicompartmental
knee arthroplasty
n=74
No tranexamic acid 178 (10.4%) 77 (9.6%) 92 (11.1%) 9 (12.2%)
Single dose i.v. 1227 (72.1%) 614 (77.0%) 565 (68.1%) 48 (64.9%)
p.o. 1 (0.1%) 0 0 1 (1.4%)
i.m. 3 (0.2%) 0 3 (0.4%) 0
Multiple doses i.v. +i.v. 226 (13.3%) 86 (10.8%) 126 (15.2%) 14 (18.9%)
p.o. +p.o. 2 (0.1%) 1 (0.1%) 1 (0.1%) 0
i.v. +top 30 (1.8%) 14 (1.8%) 14 (1.7%) 2 (2.7%)
i.v. +i.m. 3 (0.2%) 0 3 (0.4%) 0
i.v. +p.o. 31 (1.8%) 5 (0.6%) 26 (3.1%) 0
i.v., intravenous; p.o., oral; i.m., intramuscular; top, topical.
Table 2 Timing of tranexamic acid administration in all patients and those undergoing total hip, knee or unicompartmental
knee arthroplasty. Values are number (proportion).
Dose Peri-operative timing
All
n=1701
Total hip
arthroplasty
n=797
Total knee
arthroplasty
n=830
Unicompartmental
knee arthroplasty
n=74
No tranexamic acid 178 (10.4%) 77 (9.6%) 92 (11.1%) 9 (12.2%)
Single dose Pre-operative 616 (36.3%) 369 (46.3%) 228 (27.5%) 19 (25.7%)
Intra-operative 593 (34.9%) 242 (30.4%) 322 (38.7%) 29 (39.2%)
Postoperative 22 (1.3%) 3 (0.4%) 18 (2.2%) 1 (1.4%)
Multiple doses Pre-operative 1 (0.1%) 0 1 (0.1%) 0
Intra-operative 70 (4.1%) 25 (3.1%) 42 (5.1%) 3 (4.1%)
Postoperative 2 (0.1%) 1 (0.1%) 1 (0.1%) 0
Pre-operative and intra-operative 117 (6.8%) 44 (5.4%) 65 (7.8%) 8 (10.8%)
Pre-operative and postoperative 57(3.4%) 19 (2.4%) 35 (4.2%) 3 (4.1%)
Intra-operative and postoperative 45 (2.7%) 17 (2.1%) 26 (3.1%) 2 (2.7%)
Figure 3 Histogram of single doses of tranexamic acid
(n =1231)
4©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists
Anaesthesia 2020 Lloyd et al. | Peri-operative tranexamic acid in orthopaedic surgery
region (49.5%) (Fig. 4, Table S1). The rate of blood
transfusion was lowest in Northern Ireland (0%) and highest
in the Yorkshire and Humber region (7.6%) (Fig. 5, Table S2).
Discussion
Tranexamic acid was administered in approximately 90% of
patients undergoing primary hip or knee arthroplasty. The
Table 3 Anaemia prevalence, estimated blood loss and red blood cell transfusion rates in all patients and those undergoing
total hip arthroplasty, total knee arthroplasty and unicompartmental knee arthroplasty. Values are number (proportion) or mean
(SD).
All
n=1701
Total hip
arthroplasty
n=797
Total knee arthroplasty
n=830
Unicompartmental
knee arthroplasty
n=74
Proportion anaemic Hb <130 g.l
1
571 (33.6%) 290 (36.4%) 266 (32.0%) 15(20.3%)
Pre-operative haemoglobin; g.l
1
135.0 (13.5) 134.3 (13.7) 135.5 (13.3) 139 (12.1)
Postoperative haemoglobin; g.l
1
115.0 (15.3) 112.4 (15.4) 116.7 (14.8) 127 (11.3)
Estimated blood loss; ml 791.9 (452.5) 862.5 (473.3) 745.1 (423.5) 468.5 (324.8)
Red blood cell transfusion rate 54 (3.1%) 38 (4.7%) 13(1.6%) 3 (4.1%)
Esri, HERE, Garmin , (c) OpenStreetMap contri butors, and the GIS user
community
Rate (%) of
pre-op erative an aemia
22.0 - 25.0
25.1 - 30.0
30.1 - 35.0
35.1 - 40.0
40.1 - 45.0
45.1 - 50.0
Figure 4 Pre-operative anaemia prevalence by geographical region
©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Associat ion of Anaesthetists 5
Lloyd et al. | Peri-operative tranexamic acid in orthopaedic surgery Anaesthesia 2020
most frequently adopted dosing regimen was 1000 mg
delivered intravenously as a single dose either pre-
operatively or intra-operatively. Approximately one-third of
patients presented for surgery with pre-operative anaemia.
Mean estimated blood loss exceeded 500 ml for primary
total hip and knee arthroplasty in over 70% of patients. The
postoperative red blood transfusion rate for our study
cohort was 3.1%.
The results of this study demonstrate good
compliance with current NICE standards (90% of
patients administered tranexamic acid) [7]. This rate of
compliance is signicantly higher than reported in the
2016 National Comparative Audit of 471 patients
undergoing primary total hip arthroplasty and 289
undergoing primary total knee arthroplasty. In this audit,
63% of patients undergoing primary total hip
arthroplasty and 51% for primary total knee arthroplasty
received tranexamic acid [10].
There was variation in the dose, route and timing of
administration, reecting the absence of a consensus
opinion on optimal tranexamic acid dosing regimens. A
large number of randomised controlled trials have been
performed comparing different routes, doses and timing of
administration, but the heterogeneity of these studies
makes interpretation difcult in terms of determining an
optimal dose [11]. To achieve clarity, future trials examining
dosing regimens should be performed against a common
comparator that is representative of current practice. We
have demonstrated that 1000 mg of tranexamic acid given
intravenously as a single dose, either pre-operatively or
intra-operatively, would be appropriate whilst also
maintaining acceptability to clinicians.
Esri, HERE, Garmin, (c) OpenStreetMap c ontributors, and the GIS user
community
Rate (%) of allogeneic
red cell transfusion
0.8 - 2.0
2.1 - 4.0
4.1 - 6.0
6.1 - 8.0
Figure 5 Incidence of allogeneic transfusion by geographical region
6©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists
Anaesthesia 2020 Lloyd et al. | Peri-operative tranexamic acid in orthopaedic surgery
Previous studies show a reduction in blood loss and
allogeneic transfusion rates following combined topical and
intra-articular tranexamic acid compared with intravenous
alone and warrants consideration for routine clinical
practice [12]. Topical administration also overcomes
potential systemic toxicity in patients with renal failure.
Topical application was used in fewer than 2% of patients in
this cohort and always in combination with intravenous
tranexamic acid. Oral tranexamic acid administration may
offer equivalent effectiveness to intravenous and topical
administration but AT a much lower cost [13]. A concern
from in-vitro studies is potential toxicity to peri-
articular tissues when administered topically, which is
especially salient in unicompartmental knee arthroplasty
and further research is indicated to address this uncertainty
[14].
Cumulative doses of tranexamic acid ranged from 500
to 5000 mg given over 13 doses in this study. There is
inconsistent evidence of reduced blood loss with greater
doses of tranexamic acid and concerns over potential
toxicity with very high doses [15]. This study found the
majority of patients received a 1000 mg dose of
tranexamic acid rather than dosing based on patient
weight. To optimise the effectiveness of tranexamic acid,
optimal blood concentrations should be achieved early
and maintained. A 1000-mg bolus of tranexamic acid
maintains the minimal target concentration for 1.5 h after
administration [16]. While this may be effective at
addressing intra-operative blood losses, it is unlikely to
account for hidden blood losses postoperatively, which is
an important consideration in effective patient blood
management [17]. Studies have not demonstrated a
benet from multiple doses of tranexamic acid for primary
arthroplasty [6] but may play a role in revision arthroplasty
surgery with longer surgical times and greater blood loss.
Tranexamic acid was most frequently administered intra-
operatively for total knee arthroplasty and pre-operatively
for total hip arthroplasty, perhaps because tranexamic acid
is usually administered when the tourniquet is released. An
ongoing Cochrane network meta-analysis may offer further
guidance regarding tranexamic acid administration in total
hip arthroplasty and total knee arthroplasty [11].
Approximately one-third of patients in our cohort were
anaemic pre-operatively, consistent with studies from other
countries [18]. This incidence is lower than the 2016
National Comparative Audit of 726 patients, which found
50% patients were anaemic before primary total hip
arthroplasty and 60% before primary total knee arthroplasty
(Hb <130 g.l
1
men and Hb <120 g.l
1
women). There is
a national quality improvement project underway to
optimise pre-operative anaemia in orthopaedic patients
[19]. Pre-operative anaemia increases the risk of exposure to
red blood cell transfusion and is a signicant risk factor for
peri-operative morbidity and mortality [20]. Although the
World Health Organization denes anaemia as below
120 g.l
1
for women and 130 g.l
1
for men, consensus
guidance is that the threshold should be 130 g.l
1
for both
sexes [21]. Timely and effective management of pre-
operative anaemia may improve peri-operative morbidity
and functional outcomes [22, 23].
Postoperative anaemia may have signicant
implications for patient recovery. Changes in Hb
concentration >50% from baseline or postoperative
Hb <70 gl
1
have been shown to be associated with
increased risk of postoperative ischaemic events in surgical
patients [24]. The association between postoperative
anaemia and functional recovery, including patient-
reported outcome measures following surgical
interventions, remains unclear [22]. Over 80% of patients in
our sample were anaemic postoperatively, which
demonstrates that a signicant proportion of arthroplasty
patients are potentially at risk of adverse postoperative
recovery [25]. Large-scale observational studies using
epidemiological data are required to further investigate
whether this association exists.
Red blood cell transfusion rates in our sample (3.1%)
were lower than previously reported results from national
datasets (18.347%) [26], but higher than some institutional
cohort studies [2]. Transfusion rates in total joint arthroplasty
have changed signicantly in the past two decades with
development and uptake of patient blood management
strategies [27]. Restrictive transfusion thresholds have been
demonstrated to reduce rates of allogeneic transfusion with
no adverse effect on patient morbidity and mortality [28].
NICE recommends transfusion thresholds of 70 g.l
1
except in patients with acute coronary syndrome when the
threshold is 80 g.l
1
[7]. Transfusion rates following
unicompartmental knee arthroplasty (4.1%) were higher
than anticipated; however, the cohort included only 74
patients undergoing this procedure with three allogeneic
blood transfusions and is likely to represent sampling bias.
There is regional variation in the prevalence of pre-
operative anaemia and rate of postoperative transfusion.
Conclusions are limited by the small number of patients in
some regions; however, the results suggest heterogeneity
in the delivery of patient blood management despite
national guidelines [7].
Strengths of this study include utilising the power of a
trainee collaborative network [29, 30] to collect data on
current UK orthopaedic practice covering a wide
©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Associat ion of Anaesthetists 7
Lloyd et al. | Peri-operative tranexamic acid in orthopaedic surgery Anaesthesia 2020
geographical area and 56 different NHS hospitals (Fig. 1).
Approximately 130,000 primary hip and knee replacements
are performed in NHS hospitals in 2018 [31]. Our study is
estimated to have captured over a third of procedures
performed during the period of study.
Our study also has limitations. Despite widespread
collaborator recruitment and data acquisition, it is possible
that the participating centres do not represent national
practice. Selection bias may favour hospitals with
established patient blood management programmes,
underestimating allogeneic transfusion rates amongst
arthroplasty patients. The calculation of blood loss is an
estimation, although Grossformula is a validated and
accurate tool. Compliance with NICE guidance for
administering tranexamic acid may be higher than we
report, as we did not collect data to explain why tranexamic
acid was not administered. Relative contraindications to
tranexamic acid administration include thromboembolic
events and history of convulsion. Data on modes of
anaesthesia and patient comorbidity were not collected as
we focused on a small set of variables to enhance
recruitment.
In summary, we show good compliance with NICE
standards on tranexamic acid administration. The most
frequently adopted dosing regimen was 1000 mg
delivered intravenously as a single dose either pre-
operatively or intra-operatively. Future research studies may
wish to adopt this as a comparator to reduce study
heterogeneity that currently limits meta-analyses in this
eld.
Acknowledgements
We thank Dr A. Shah for his help with the preparation and
critical appraisal of this manuscript. Funding support for this
study was received from the National Institute for Health
Research (NIHR) Oxford Biomedical Research Centre. No
other external funding or competing interests declared.
Appendix: collaborators.
J. Wong, P. Sharma, P. K. Osei-Bonsu, G. Ashcroft
(Aberdeen Royal Inrmary/Woodend General Hospital); T.
Baigent, E. Shirland (Addenbrookes Hospital); R. Espey,
M. Stokes (Altnagelvin Area Hospital); I. Liew, A. Dhawal,
D. Watchorn (Arrowe Park/Clatterbridge Hospitals); J.
Lum, M. Qureshi, A. S. Khaled (Blackpool Victoria
Hospital); S. Kauser (Bradford Royal Inrmary); G.
Hodhody, S. Rogers, B. Haywood-Alexander, G. Sheikh
(Burnley General Hospital/Royal Blackburn Hospital); P.
Mahapatra, H. Twaij, M. Chicco (Central Middlesex
Hospital); F. Arnaout, T. Atherton, J. Mutimer (Cheltenham
General Hospital); P. Sinha, E. Oliver (Darent Valley
Hospital); T. Stedman, R. Gadd (Doncaster Royal Inrmary);
V. Kutuzov, M. Sattar (Dr Grays Hospital); L. Robiati (Royal
Inrmary of Edinburgh; Victoria Hospital, Kirkcaldy); Ricci
Plastow (Faireld General Hospital); T. Howe, A. Hassan
(Frimley Park Hospital); B. Lau, J. Collins (Guys and St.
ThomasHospital); A. Doshi (Hull Royal Inrmary); G. Tan,
D. Baskaran, K. Hari Sunil Kumar (Ipswich Hospital); R.
Agarwal (Llandough Hospital); M. Horner, R. Gwyn, S.
Masud (Morriston Hospital); O. Beaumont (Musgrove Park
Hospital); A. Pilarski (New Cross Hospital); M. Lebe, S.
Dawson-Bowling, D. Nolan, K. Tsitskaris (Newham General
Hospital); R. E. Beamish, C. Jordan, S. Alsop, E. Hibbert, G.
Deshpande, A. Gould, T. Briant-Evans, L. Kilbane (North
Hampshire General Hospital); I. Crowther, H. Ingoe, A.
Naisbitt (Northumbria Healthcare NHS Trust); L. Gourbault,
J. Muscat, E. L. Goh, (Nufeld Orthopaedic Centre); J. Gill,
M. Elbashir, N. Modi (Peterborough City Hospital); J.
Archer (Princess Royal Hospital Telford); S. Ismael (Russel
Hall Hospital); M. Petrie, H. OBrien (Rotherham General
Hospital); M. McCormick, N. P. Koh (Royal Alexandra
Hospital); T. Lloyd (Royal Berkshire Hospital); A. King
(Royal Cornwall Hospital); A. Ikram, J. Peake (Royal Derby
Hospital); A. Yoong, D. S. Rye (Royal Devon and Exeter
Hospital); M. Newman (Royal Hampshire County Hospital);
A. Naraen, D. Myatt (Royal Preston Hospital); R. Kapur, P.
Sgardelis (Royal United Hospital); S. Kohli, M.
Culverhouse-Mathews (Salisbury District Hospital); S.
Haynes, H. Boden, A. Purmah (Sandwell District General
Hospital); R. Shenoy, S. Raja (Southend Hospital); N. P. Koh
(Southern General Hospital/Queen Elizabeth University
Hospital); R. Donovan, D. Yeomans, D. Ritchie, R. Larkin
(Southmead Hospital); R. Aladwan, K. Hughes (St. Richards
Hospital); R. Unsworth, R. Cooke, I. Samra, J. Barrow, K
Michael, F. Byrne (Stepping Hill Hospital); R. Anwar, L.
Karatzia, H. Drysdale, H. Wilson (Stoke Mandeville
Hospital/Wycombe General Hospital); R. Jones (Torbay
Hospital); D. Dass, F. Liaw (University Hospital of North
Staffordshire); R. Aujla, A. Kheiran (University Hospitals of
Leicester NHS Trust); K. Bell (Victoria Hospital, Kirkcaldy);
A. L. Ramavath, R. Telfer (Whiston Hospital); K. Nachev
(William Harvey Hospital); H. Lawrence, V. Garg, P. Shenoy,
A. Lacey, I. Byrom, M. Simons (Wrexham Maelor Hospital);
C. Manning, N. Cheyne, J. Williams (Wythenshawe
Hospital).
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Supporting Information
Additional supporting information may be found online via
the journal website.
Table S1. Pre-operative anaemia prevalence by
geographical region
Table S2. Incidence of allogeneic transfusion by
geographical region
©2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Associat ion of Anaesthetists 9
Lloyd et al. | Peri-operative tranexamic acid in orthopaedic surgery Anaesthesia 2020
... 17,27 The 24% of preoperative anemia (Hb <13 g/dL) identified is similar to the 12-33% already described in patients undergoing TKA. 28,29 Preoperative anemia is the most important independent risk factor for transfusion and perioperative morbidity and mortality. 30 Postoperative anemia was 91%, higher than the 82% observed in another study. ...
... 30 Postoperative anemia was 91%, higher than the 82% observed in another study. 29 Our study presents some limitations: It is a retrospective study; the choice of blood sparing strategy was made according to surgeon's preference, which can cause some group biases not analysed by this study; even though the ideal dose of tranexamic acid remains a subject of discussion, the difference between the dose of tranexamic acid in the two protocols (15mg/kg in the TXA-iv group vs 1500mg TXA-art) can contribute as bias of analysis considering patient's weight. We tried to minimize this by analysing differences in groups' BMI; the wide interval of transfusion threshold (Hb 8-10g/dL) was based on a subjective clinical evaluation which can translate as a limitation on the interpretation of the presented findings. ...
Article
Full-text available
Purpose: Total knee arthroplasty is associated with considerable perioperative hemorrhage. The decrease in hemoglobin concentration and the need for allogenic blood transfusion are related to increased morbidity and mortality. Strategies for minimizing perioperative bleeding are used, such as tranexamic acid and cell salvage. The study aimed to compare intravenous, intra-articular tranexamic acid and cell salvage protocols regarding perioperative hemoglobin variation. Secondary outcomes included blood loss; allogenic transfusions; complications and in-hospital stay. Patients and methods: Patients submitted to unilateral total knee arthroplasty between January and December 2018 were retrospectively evaluated. After excluding 62 patients, 204 were subdivided into 3 groups according to the protocol used. Statistical analysis was performed with SPSS version 26.0. One-way ANOVA and Kruskal-Wallis tests were used. Considered a p-value of <0.05 for statistical significance. Results: Variation of hemoglobin in the intra-articular tranexamic acid group was significantly lower than that of intravenous (p < 0.001) and cell salvage (p = 0.001) groups. Blood loss, variation of hematocrit, need for blood transfusion and in-hospital stay were also statistically significantly lower in the intra-articular tranexamic acid group. The only related complications were in the intravenous tranexamic acid group. No thromboembolic complications were identified which further solidifies the safety of tranexamic acid administration. Conclusion: This data shows superiority of the intra-articular administration of tranexamic acid over the other techniques in total knee arthroplasty. We propose this protocol as an efficient, low-risk blood-sparing strategy.
... 6 Despite blood conservation strategies, over 80% of patients are anaemic on discharge from hospital and up to 5% require allogenic red blood cell transfusion. [7][8][9][10] The recommended haemoglobin concentration (Hb) threshold for administering allogeneic red blood post-operatively is 70 g/L, or 80 g/L in the presence of acute coronary syndrome. 11 Routine clinical practice is to perform group and save (G&S) in all patients prior to arthroplasty surgery and a post-operative blood test for Hb prior to discharge from hospital, however, there is limited guidance for when these investigations are indicated or can be omitted. ...
Article
Full-text available
Objective: Assess the prognostic value of pre-operative haemoglobin concentration (Hb) for identifying patients who develop severe post-operative anaemia or require blood transfusion following primary total hip or knee, or unicompartmental knee arthroplasty (THA, TKA, UKA). Background: Pre-operative group and save (G&S), and post-operative Hb measurement may be unnecessary for many patients undergoing hip and knee arthroplasty provided individuals at greatest risk of severe post-operative anaemia can be identified. Methods and materials: Patients undergoing THA, TKA, or UKA between 2011 and 2018 were included. Outcomes were post-operative Hb below 70 and 80 g/L, and peri-operative blood transfusion. Logistic regression assessed the association between pre-operative Hb and each outcome. Decision curve analysis compared strategies for selecting patients for G&S and post-operative Hb measurement. Results: 10 015 THA, TKA and UKA procedures were performed in 8582 patients. The incidence of blood transfusion (4.5%) decreased during the study. Using procedure specific Hb thresholds to select patients for pre-operative G&S and post-operative Hb testing had a greater net benefit than selecting all patients, no patients, or patients with pre-operative anaemia. Conclusions: Pre-operative G&S and post-operative Hb measurement may not be indicated for UKA or TKA when adopting restrictive transfusion thresholds, provided clinicians accept a 0.1% risk of patients developing severe undiagnosed post-operative anaemia (Hb < 70 g/L). The decision to perform these blood tests for THA patients should be based on local institutional data and selection of acceptable risk thresholds.
... However, there remains the risk of displacement of fractures resulting in malunion, need for further surgery, and early-onset ankle arthritis [5,6]. Multiple recent studies have utilized the power of trainee research collaborative (TRC) networks to gather data from a large number of patients from hospitals across wide geographical areas in a short period [4,7,8]. ...
Article
Full-text available
Aim The purpose of this all Wales national audit was to compare compliance against British Orthopedic Association Standards for Trauma (BOAST) guidelines on the management of ankle fractures. Methods A multi-center prospective audit of the management of adult ankle fractures was conducted between February 2, 2020, and February 17, 2020, via the Welsh Orthopedic Research Collaborative (WORC). Regional leads were recruited in nine NHS hospitals across six university health boards, and recruited collaborators in their respective hospitals. Questionnaires for the data collection on both surgical and conservative management were made available via a password-protected website (walesortho.co.uk). We defined early weight-bearing (EWB) as unrestricted weight-bearing on the affected leg within three weeks of injury or surgery and delayed weight-bearing (DWB) as unrestricted weight-bearing after three weeks of injury or surgery. Results A total of 28 collaborators contributed data for 238 ankle fractures. Poor documentation at the time of injury was noted. Less than 50% of patients with posterior malleolus fracture had a CT scan for further evaluation. Eighty-four percent of the non-operatively treated patients did not have a weight-bearing X-ray (WBXR). Patients who had a WBXR were more likely to be allowed EWB but this was not statistically significant. EWB was allowed in 59.43% and 10% of the non-operatively and operatively treated patients, respectively. DWB was higher in patients who had fixation of the posterior malleolus or syndesmosis. Conclusion There is poor compliance with BOAST guidelines on the management of ankle fractures across Wales. We need to improve documentation and also consider performing a CT scan when the posterior malleolus is fractured. A weight-bearing X-ray should be performed more often to ascertain the stability of an ankle fracture, and those that are deemed stable should be treated with early weight-bearing. The guidelines need to be clearer regarding weight-bearing after fixation especially when posterior malleolus and/or syndesmosis are fixed.
... It is recommended in surgeries with an expected blood loss of more than 500 mL. 3 TXA administration reduces mortality in bleeding trauma patients and in postpartum hemorrhage. 4,5 There is also evidence for TXA in other scenarios, such as cardiovascular surgery, patients with liver disease undergoing invasive surgery or procedures with risk of bleeding, and patients with acute hemorrhagic pathology; however, further studies are required before it can be routinely indicated. ...
Article
Full-text available
Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce peri-operative bleeding needs to be standardized. Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, cardiac, trauma and obstetric surgery.
... 1 Up to one in three of those patients would be expected to have preoperative anaemia, the majority of which is caused by absolute or functional iron deficiency in this population. [2][3][4][5][6] Preoperative anaemia is an independent risk factor for increased perioperative complications, mortality, allogenic red blood cell (RBC) transfusion and longer length of hospital stay (LoS). 7 RBC transfusion itself is also independently associated with poorer postoperative outcomes and longer LoS. ...
Article
Full-text available
Objectives Preoperative anaemia is associated with increased risks of postoperative complications, blood transfusion and mortality. This meta-analysis aims to review the best available evidence on the clinical effectiveness of preoperative iron in anaemic patients undergoing elective total hip (THR) or total knee replacement (TKR). Design Electronic databases and handsearching were used to identify randomised and non-randomised studies of interventions (NRSI) reporting perioperative blood transfusion rates for anaemic participants receiving iron before elective THR or TKR. Searches of CENTRAL, MEDLINE, Embase, PubMed and other databases were conducted on 17 April 2019 and updated on 15 July 2020. Two investigators independently reviewed studies for eligibility and evaluated risk of bias using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and a modified Newcastle-Ottawa scale for NRSIs. Data extraction was performed by ABS and checked by AB. Meta-analysis used the Mantel-Haenszel method and random-effects models. Results 807 records were identified: 12 studies met the inclusion criteria, of which 10 were eligible for meta-analyses (one RCT and nine NRSIs). Five of the NRSIs were of high-quality while there were some concerns of bias in the RCT. Meta-analysis of 10 studies (n=2178 participants) showed a 39% reduction in risk of receiving a perioperative blood transfusion with iron compared with no iron (risk ratio 0.61, 95% CI 0.50 to 0.73, p<0.001, I ² =0%). There was a significant reduction in the number of red blood cell units transfused with iron compared with no iron (mean difference −0.37units, 95% CI −0.47 to -0.27, p<0.001, I ² =40%); six studies (n=1496). Length of stay was significantly reduced with iron, by an average of 2.08 days (95% CI −2.64 to −1.51, p<0.001, I ² =40%); five studies (n=1140). Conclusions Preoperative iron in anaemic, elective THR or TKR patients, significantly reduces the number of patients and number of units transfused and length of stay. However, high-quality, randomised trials are lacking. PROSPERO registration number CRD42019129035.
Article
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Background: Concerns regarding the safety and availability of transfused donor blood have prompted research into a range of techniques to minimise allogeneic transfusion requirements. Cell salvage (CS) describes the recovery of blood from the surgical field, either during or after surgery, for reinfusion back to the patient. Objectives: To examine the effectiveness of CS in minimising perioperative allogeneic red blood cell transfusion and on other clinical outcomes in adults undergoing elective or non-urgent surgery. Search methods: We searched CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers for randomised controlled trials (RCTs) and systematic reviews from 2009 (date of previous search) to 19 January 2023, without restrictions on language or publication status. Selection criteria: We included RCTs assessing the use of CS compared to no CS in adults (participants aged 18 or over, or using the study's definition of adult) undergoing elective (non-urgent) surgery only. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: We included 106 RCTs, incorporating data from 14,528 participants, reported in studies conducted in 24 countries. Results were published between 1978 and 2021. We analysed all data according to a single comparison: CS versus no CS. We separated analyses by type of surgery. The certainty of the evidence varied from very low certainty to high certainty. Reasons for downgrading the certainty included imprecision (small sample sizes below the optimal information size required to detect a difference, and wide confidence intervals), inconsistency (high statistical heterogeneity), and risk of bias (high risk from domains including sequence generation, blinding, and baseline imbalances). Aggregate analysis (all surgeries combined: primary outcome only) Very low-certainty evidence means we are uncertain if there is a reduction in the risk of allogeneic transfusion with CS (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.59 to 0.72; 82 RCTs, 12,520 participants). Cancer: 2 RCTs (79 participants) Very low-certainty evidence means we are uncertain whether there is a difference for mortality, blood loss, infection, or deep vein thrombosis (DVT). There were no analysable data reported for the remaining outcomes. Cardiovascular (vascular): 6 RCTs (384 participants) Very low- to low-certainty evidence means we are uncertain whether there is a difference for most outcomes. No data were reported for major adverse cardiovascular events (MACE). Cardiovascular (no bypass): 6 RCTs (372 participants) Moderate-certainty evidence suggests there is probably a reduction in risk of allogeneic transfusion with CS (RR 0.82, 95% CI 0.69 to 0.97; 3 RCTs, 169 participants). Very low- to low-certainty evidence means we are uncertain whether there is a difference for volume transfused, blood loss, mortality, re-operation for bleeding, infection, wound complication, myocardial infarction (MI), stroke, and hospital length of stay (LOS). There were no analysable data reported for thrombosis, DVT, pulmonary embolism (PE), and MACE. Cardiovascular (with bypass): 29 RCTs (2936 participants) Low-certainty evidence suggests there may be a reduction in the risk of allogeneic transfusion with CS, and suggests there may be no difference in risk of infection and hospital LOS. Very low- to moderate-certainty evidence means we are uncertain whether there is a reduction in volume transfused because of CS, or if there is any difference for mortality, blood loss, re-operation for bleeding, wound complication, thrombosis, DVT, PE, MACE, and MI, and probably no difference in risk of stroke. Obstetrics: 1 RCT (1356 participants) High-certainty evidence shows there is no difference between groups for mean volume of allogeneic blood transfused (mean difference (MD) -0.02 units, 95% CI -0.08 to 0.04; 1 RCT, 1349 participants). Low-certainty evidence suggests there may be no difference for risk of allogeneic transfusion. There were no analysable data reported for the remaining outcomes. Orthopaedic (hip only): 17 RCTs (2055 participants) Very low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, or if there is any difference between groups for mortality, blood loss, re-operation for bleeding, infection, wound complication, prosthetic joint infection (PJI), thrombosis, DVT, PE, stroke, and hospital LOS. There were no analysable data reported for MACE and MI. Orthopaedic (knee only): 26 RCTs (2568 participants) Very low- to low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, and whether there is a difference for blood loss, re-operation for bleeding, infection, wound complication, PJI, DVT, PE, MI, MACE, stroke, and hospital LOS. There were no analysable data reported for mortality and thrombosis. Orthopaedic (spine only): 6 RCTs (404 participants) Moderate-certainty evidence suggests there is probably a reduction in the need for allogeneic transfusion with CS (RR 0.44, 95% CI 0.31 to 0.63; 3 RCTs, 194 participants). Very low- to moderate-certainty evidence suggests there may be no difference for volume transfused, blood loss, infection, wound complication, and PE. There were no analysable data reported for mortality, re-operation for bleeding, PJI, thrombosis, DVT, MACE, MI, stroke, and hospital LOS. Orthopaedic (mixed): 14 RCTs (4374 participants) Very low- to low-certainty evidence means we are uncertain if there is a reduction in the need for allogeneic transfusion with CS, or if there is any difference between groups for volume transfused, mortality, blood loss, infection, wound complication, PJI, thrombosis, DVT, MI, and hospital LOS. There were no analysable data reported for re-operation for bleeding, MACE, and stroke. Authors' conclusions: In some types of elective surgery, cell salvage may reduce the need for and volume of allogeneic transfusion, alongside evidence of no difference in adverse events, when compared to no cell salvage. Further research is required to establish why other surgeries show no benefit from CS, through further analysis of the current evidence. More large RCTs in under-reported specialities are needed to expand the evidence base for exploring the impact of CS.
Article
Background: Blood transfusion can be a lifesaving intervention after perioperative blood loss. Many prediction models have been developed to identify patients most likely to require blood transfusion during elective surgery, but it is unclear whether any are suitable for clinical practice. Study design and setting: We conducted a systematic review, searching MEDLINE, Embase, PubMed, The Cochrane Library, Transfusion Evidence Library, Scopus, and Web of Science databases for studies reporting the development or validation of a blood transfusion prediction model in elective surgery patients between 01/01/2000 to 30/06/2021. We extracted study characteristics, discrimination performance (c-statistics) of final models and data which we used to perform risk of bias assessment using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Results: We reviewed 66 studies (72 developed and 48 externally validated models). Pooled c-statistics of externally validated models ranged from 0.67 to 0.78. Most developed and validated models were at high risk of bias due to handling of predictors, validation methods, and too small sample sizes. Conclusion: Most blood transfusion prediction models are at high risk of bias and suffer from poor reporting and methodological quality, which must be addressed before they can be safely used in clinical practice.
Article
Aims: Routinely collected patient-reported outcome measures (PROMs) have been useful to quantify and quality-assess provision of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in the UK for the past decade. This study aimed to explore whether the outcome following primary THA and TKA had improved over the past seven years. Methods: Secondary data analysis of 277,430 primary THAs and 308,007 primary TKAs from the NHS PROMs programme was undertaken. Outcome measures were: postoperative Oxford Hip/Knee Score (OHS/OKS); proportion of patients achieving a clinically important improvement in joint function (responders); quality of life; patient satisfaction; perceived success; and complication rates. Outcome measures were compared based on year of surgery using multiple linear and logistic regression models. Results: For primary THA, multiple linear regression modelling found that more recent year of surgery was associated with higher postoperative OHS (unstandardized coefficient (B) 0.15 points (95% confidence interval (CI) 0.14 to 0.17); p < 0.001) and higher EuroQol five-dimension index (EQ-5D) utility (B 0.002 (95% CI 0.001 to 0.002); p < 0.001). The odds of being a responder (odds ratio (OR) 1.02 (95% CI 1.02 to 1.03); p < 0.001) and patient satisfaction (OR 1.02 (95% CI 1.01 to 1.03); p < 0.001) increased with year of surgery, while the odds of any complication reduced (OR 0.97 (95% CI 0.97 to 0.98); p < 0.001). No trend was found for perceived success (p = 0.555). For primary TKA, multiple linear regression modelling found that more recent year of surgery was associated with higher postoperative OKS (B 0.21 points (95% CI 0.19 to 0.22); p < 0.001) and higher EQ-5D utility (B 0.002 (95% CI 0.002 to 0.003); p < 0.001). The odds of being a responder (OR 1.04 (95% CI 1.03 to 1.04); p < 0.001), perceived success (OR 1.02 (95% CI 1.01 to 1.02); p < 0.001), and patient satisfaction (OR 1.02 (95% CI 1.01 to 1.02); p < 0.001) all increased with year of surgery, while the odds of any complication reduced (OR 0.97 (95% CI 0.97 to 0.97); p < 0.001). Conclusion: Nearly all patient-reported outcomes following primary THA/TKA improved by a small amount over the past seven years. Due to the high proportion of patients achieving good outcomes, PROMs following THA and TKA may need to focus on better discrimination of patients achieving high scores to be able to continue to measure improvement in outcomes. Cite this article: Bone Joint J 2022;104-B(6):687-695.
Article
Background Total joint arthroplasty (TJA) is a very successful orthopedics procedure but associates with a significantly high transfusion rate. Objective In this study, we aimed to determine predictors of postoperative blood transfusion in patients undergoing elective hip and knee TJA patients and compare the accuracy of machine learning (ML) algorithms in predicting transfusion risk. Methods We utilized data from 12,642 patients undergoing primary unilateral TJA. Risk factors and demographic information were extracted, and predictive models were developed using seven ML algorithms. The area under the receiver operating characteristic curve was used to measure the predictive accuracy of each algorithm. Results The overall transfusion rate was 18.7%. Patient-related risk factors for transfusion included age 65–85 (Odds Ratio (OR): 1.175–1.222), female (OR: 1.246), American Society of Anesthesiologists grade Ⅱ or greater (OR: 1.264–2.758). Surgical factors included operation time (OR: 1.736), drain use (OR: 2.202) as well as intraoperative blood loss (OR: 7.895). Elevated preoperative Hb (OR: 0.615), Hct (OR: 0.800), BMI (≥24kg/m²) (OR: 0.613–0.731) and tranexamic acid use (OR: 0.375) were associated with decreased risk of postoperative transfusion. The long short-term memory networks (LSTM) and random forest (RF) models achieved the highest predictive accuracy (p < 0.001). Conclusion The risk factors identified in the current study can provide specific, personalized postoperative transfusion risk assessment for a patient considering lower limb TJA. Furthermore, the predictive accuracies of LSTM and RF algorithms were significantly higher than the others, making them potential tools for future personalized preoperative prediction of risk for postoperative transfusion.
Article
Background The purpose of this study was to compare total blood loss and the risk of receiving a blood transfusion in robotic-assisted total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) against conventional jig-based techniques Methods Robotic TKA (n=50) and UKA (n=50) patients were matched to contemporary controls for TKA (n=50) and UKA (n=50) and retrospectively analysed Results Robotic TKA patients experienced 23.7% less blood loss compared to conventional TKA patients (911.0ml vs 1193.7ml, p<0.01), and were associated with an 83% relative risk reduction of receiving a transfusion (2% of patients vs 12%, p=0.02). Robotic UKA patients did not demonstrate less blood loss compared to corresponding controls (821.7ml vs 854.7ml, p=0.69). Both UKA groups received no transfusions Conclusions Robotic surgical systems in TKA reduces blood loss and lowers the risk of requiring a blood transfusion. In UKA, robotic-assisted arthroplasty did not reduce blood loss compared to conventional arthroplasty. This article is protected by copyright. All rights reserved.
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Pregnant women should receive information about what they might expect to experience during their delivery. Despite this, research shows many women are inadequately prepared for anaesthetic interventions during labour. We surveyed 903 postnatal women across 28 Greater London hospitals about: the analgesic and anaesthetic information that they recalled receiving during pregnancy and delivery; their confidence to make decisions on analgesia; and their satisfaction with the analgesia used. Wide variation was observed between hospitals. Overall, 67 of 749 (9.0%) women recalled receiving antenatal information covering all aspects of labour analgesia, and 108 of 889 (12.1%) covering anaesthesia for caesarean section. Regarding intrapartum information, 256 of 415 (61.7%) respondents recalled receiving thorough information before epidural insertion for labour analgesia, and 102 of 370 (27.6%) before anaesthesia for caesarean section. We found that 620 of 903 (68.7%) women felt well enough informed to be confident in their analgesic choices, and 675 of 903 (74.8%) stated that their analgesia was as expected or better. Receiving information verbally, regardless of provider, was the factor most strongly associated with respondents recalling receiving full information: odds ratio (95%CI) for labour analgesia 20.66 (8.98–47.53; p < 0.0001); epidural top‐up for caesarean section 5.93 (1.57–22.35; p = 0.01); and general anaesthesia for caesarean section 12.39 (2.18–70.42; p = 0.01). A large proportion of respondents did not recall being fully informed before an anaesthetic intervention. Collaboration with current antenatal service providers, both in promoting information delivery and providing resources to assist with delivery, could improve the quality of information offered and women's retention of that information.
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Total blood loss from primary total knee arthroplasty may exceed 2 L with greater blood loss during revision procedures. Blood loss and allogeneic transfusion are strongly associated with adverse outcomes from surgery including postoperative mortality, thromboembolic events and infection. Strategies to reduce blood loss and transfusion rates improve patient outcomes and reduce healthcare costs. Interventions are employed preoperatively, intraoperatively and postoperatively. The strongest predictor for allogeneic blood transfusion is preoperative anaemia. Over 35% of patients are anaemic when scheduled for primary and revision knee arthroplasty, defined as haemoglobin <130 g/L for men and women, and the majority of cases are secondary to iron deficiency. Early identification and treatment of anaemia can reduce postoperative transfusions and complications. Anticoagulation must be carefully managed perioperatively to balance the risk of thromboembolic event versus the risk of haemorrhage. Intraoperatively, tranexamic acid reduces blood loss and is recommended for all knee arthroplasty surgery; however, the optimal route, dose or timing of administration remains uncertain. Cell salvage is a valuable adjunct to surgery with significant expected blood loss, such as revision knee arthroplasty. Autologous blood donation is not recommended in routine care, sealants may be beneficial in select cases but further evidence of benefit is required, and the use of a tourniquet remains at the discretion of the surgeon. Postoperatively, restrictive transfusion protocols should be followed with a transfusion threshold haemoglobin of 70 g/L, except in the presence of acute coronary syndrome. Recent studies report no allogeneic transfusions after primary knee arthroplasty surgery after employing blood conservation strategies. The current challenge is to select and integrate different blood conserving interventions to deliver an optimal patient pathway with a multidisciplinary approach.
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Background: Reducing operative blood loss improves patient outcomes and reduces healthcare costs. The aim of this article was to review current surgical, anaesthetic and haemostatic intraoperative blood conservation strategies. Methods: This narrative review was based on a literature search of relevant databases up to 31 July 2019 for publications relevant to reducing blood loss in the surgical patient. Results: Interventions can begin early in the preoperative phase through identification of patients at high risk of bleeding. Directly acting anticoagulants can be stopped 48 h before most surgery in the presence of normal renal function. Aspirin can be continued for most procedures. Intraoperative cell salvage is recommended when anticipated blood loss is greater than 500 ml and this can be continued after surgery in certain situations. Tranexamic acid is safe, cheap and effective, and routine administration is recommended when anticipated blood loss is high. However, the optimal dose, timing and route of administration remain unclear. The use of topical agents, tourniquet and drains remains at the discretion of the surgeon. Anaesthetic techniques include correct patient positioning, avoidance of hypothermia and regional anaesthesia. Permissive hypotension may be beneficial in selected patients. Promising haemostatic strategies include use of pharmacological agents such as desmopressin, prothrombin complex concentrate and fibrinogen concentrate, and use of viscoelastic haemostatic assays. Conclusion: Reducing perioperative blood loss requires a multimodal and multidisciplinary approach. Although high-quality evidence exists in certain areas, the overall evidence base for reducing intraoperative blood loss remains limited.
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Blood transfusion is one of the most common hospital procedures in developed countries. However, inappropriate use of blood transfusion is common, and this is of considerable concern because transfusion is known to be associated with adverse events and is costly. Reductions in blood use have resulted from recent evidence indicating that restrictive use of red blood cell transfusions is associated with similar patient outcomes to liberal strategies and from a focus on patient blood management (PBM), which recognizes the importance of conserving the patient’s own blood alongside the judicious use of transfusion. A recent Consensus Conference in Frankfurt developed practice and research recommendations for PBM but also indicated that additional studies are needed to provide better evidence for PBM interventions, including for improved patient outcomes and lower hospital costs as well as for reductions in blood utilization. In the meanwhile, it is of utmost importance to translate PBM guidelines into practical day-to-day recommendations and encourage their use to make PBM “the standard of care.”
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The peri-operative use of angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers is thought to be associated with an increased risk of postoperative acute kidney injury. To reduce this risk, these agents are commonly withheld during the peri-operative period. This study aimed to investigate if withholding angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers peri-operatively reduces the risk of acute kidney injury following major non-cardiac surgery. Patients undergoing elective major surgery on the gastrointestinal tract and/or the liver were eligible for inclusion in this prospective study. The primary outcome was the development of acute kidney injury within seven days of operation. Adjusted multi-level models were used to account for centre-level effects and propensity score matching was used to reduce the effects of selection bias between treatment groups. A total of 949 patients were included from 160 centres across the UK and Republic of Ireland. From this population, 573 (60.4%) patients had their angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers withheld during the peri-operative period. One hundred and seventy-five (18.4%) patients developed acute kidney injury; there was no difference in the incidence of acute kidney injury between patients who had their angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers continued or withheld (107 (18.7%) vs. 68 (18.1%), respectively; p = 0.914). Following propensity matching, withholding angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers did not demonstrate a protective effect against the development of postoperative acute kidney injury (OR (95%CI) 0.89 (0.58-1.34); p = 0.567).
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This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route. © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Objectives Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Methods Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. Results There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. Conclusion The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations.
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Aims Despite declining frequency of blood transfusion and electrolyte supplementation following total joint arthroplasty, postoperative blood analyses are still routinely ordered for these patients. This study aimed to determine the rate of blood transfusion and electrolyte restoration in arthroplasty patients treated with a perioperative blood conservation protocol and to identify risk factors that would predict the need for transfusion and electrolyte supplementation. Patients and Methods Patients undergoing primary total joint arthroplasty of the hip or knee between July 2016 and February 2017 at a single institution were included in the study. Standard preoperative and postoperative laboratory data were collected and reviewed retrospectively. A uniform blood conservation programme was implemented for all patients. Need for blood transfusion or potassium supplementation was determined through a coordinated decision by the care team. Rates of transfusion and supplementation were observed, and patient risk factors were noted. Results The overall rate of blood transfusion was 1.06% in the study population of 1132 total joint arthroplasties performed in 1023 patients. Of the 12 patients requiring transfusion, 11 were female, ten occurred in patients undergoing total hip arthroplasty, and all 12 patients had a preoperative haemoglobin level less than 130 g/l. Operative duration and surgical blood loss were significantly greater in those patients requiring blood transfusion. Nearly all patients requiring transfusion had a history of, or risk factors for, cardiovascular disease. Potassium supplementation was required in 15.5% of the study cohort; 72% of these patients receiving potassium presented with a potassium level less than 4 mmol/l during preoperative testing, while the remaining 28% had a past medical history of either significant anaemia, cardiopulmonary, cardiovascular, or renal diseases that had required substantial medical management. Conclusion A consistent blood-conserving perioperative strategy effectively minimized need for blood transfusion in total joint arthroplasty patients below previously reported rates in the literature. We suggest that postoperative full blood counts and basic metabolic panels should not routinely be ordered in these patients unless their preoperative haemoglobin and potassium is below 130 g/dl or 4 mmol/l respectively, and they have medical comorbidities.
Article
Objectives: Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Methods: Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. Results: There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. Conclusion: The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations.Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11-18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1.
Article
Aims: The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA). Patients and methods: In this randomized controlled trial, 200 patients were randomized to receive a single dose of 2.0 g of TXA orally two hours preoperatively (group A), a single dose of TXA followed by 1.0 g orally three hours postoperatively (group B), a single dose of TXA followed by 1.0 g three and nine hours postoperatively (group C), or a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (group D). All patients followed a routine enhanced-recovery protocol. The primary outcome measure was the total blood loss. Secondary outcome measures were hidden blood loss (HBL), reduction in the level of haemoglobin, the rate of transfusion and adverse events. Results: Groups C (661.1 ml, sd 262.4) and D (597.7 ml, sd 219.6) had significantly lower mean total blood loss compared with groups A and B. The mean HBL was significantly lower in groups B (699.2 ml), C (533.1 ml) and D (469.9 ml) than in group A (p = 0.006, p < 0.001, and p < 0.001, respectively). Groups C (2.22 ml, sd 0.91) and D (2.04 ml, sd 0.95) had a lower reduction in the level of haemoglobin than groups A and B. However, there were no differences between groups C and D in relation to the three parameters. Conclusion: The addition of two or three postoperative doses of TXA to one preoperative dose produced a significant reduction in blood loss. The two-dose postoperative regimen is the least necessary regimen for clinical efficacy in primary unilateral TKA. The three-dose regimen produced maximum reduction of blood loss. Cite this article: Bone Joint J 2018;100-B:1025-32.