Interventions For Preventing Venous Thromboembolism in Adults Undergoing Knee Arthroscopy (Review)

Interventions for preventing venous thromboembolism in
adults undergoing knee arthroscopy (Review)

Ramos J, Perrotta C, Badariotti G, Berenstein G
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2011, Issue 3
http://www.thecochranelibrary.com
Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy (Review)
Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13
Analysis 1.1. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 1 Participants with
thrombotic events (both clinical and through diagnostic procedure). . . . . . . . . . . . . . . .
13
Analysis 1.2. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 2 Participants with clinical
thrombotic events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14
Analysis 1.3. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 3 Participants with adverse
events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
15
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
15
FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
16
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
16
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17
INDEX TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18
[Intervention Review]
Interventions for preventing venous thromboembolism in

adults undergoing knee arthroscopy
Jorge Ramos1 , Carla Perrotta2 , Gustavo Badariotti3 , Graciela Berenstein4
1 Department of Orthopedics, Hospital Britnico de Buenos Aires, Buenos Aires, Argentina. 2 Woodview House, UCD School of Public
Health and Population Sciences, Dublin, Ireland. 3 Internal Medicine, Sanatorio Mater Dei, Buenos Aires, Argentina. 4 Epidemiology
Department, Hospital Nacional Dr Alejandro Posadas, Buenos Aires, Argentina
Contact address: Jorge Ramos, Department of Orthopedics, Hospital Britnico de Buenos Aires, Dorrego 1471, Victoria, Buenos Aires,
CP 1644, Argentina. jorgeramosmd@yahoo.com.
Editorial group: Cochrane Peripheral Vascular Diseases Group.
Publication status and date: Edited (no change to conclusions), published in Issue 3, 2011.
Review content assessed as up-to-date: 13 December 2006.
Citation: Ramos J, Perrotta C, Badariotti G, Berenstein G. Interventions for preventing venous thromboembolism in
adults undergoing knee arthroscopy. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD005259. DOI:
10.1002/14651858.CD005259.pub3.
ABSTRACT
Background
Knee arthroscopy is a frequent surgical procedure. Arthroscopy procedures are considered minimally invasive. However, some patients
will need extended surgical time, suffer injury and immobilization thus increasing the risk for thromboembolic events. Incidence of
deep venous thrombosis (DVT) in patients undergoing knee arthroscopy is reported to be from 0.6% to 17.9% depending on the
diagnostic method used. Different approaches are available for thromboprophylaxis (mechanical or pharmacological).
Objectives
To assess the effectiveness and safety of thromboprophylaxis to reduce the incidence of DVT in patients undergoing knee arthroscopy.
Search methods
We searched the Cochrane Peripheral Vascular Diseases Group Specialized Register (last searched October 2006) the CENTRAL (last
searched Issue 4, 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), and Lilacs (1988 to 2006). We contacted specialists
known to be involved in phlebology and interested in post thrombotic syndrome for details of unpublished and ongoing trials.
Selection criteria
Randomized clinical trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not (i.e. double blinded, single blinded or
unblinded) of all type of interventions, whether mechanical or pharmacological, single or in combination, used to prevent DVT in
males and females over 18 years old undergoing knee arthroscopy. There was no restriction on language.
Data collection and analysis
Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.
Main results
Four trials involving 527 predominantly male participants were included. The main weakness of the studies was the lack of correct
stratification of the arthroscopic intervention.
The relative risk (RR) of thrombotic events was 0.16 (95% confidence interval (CI); 0.05 to 0.52) comparing any type of low molecular
weight heparin (LMWH) versus placebo. All thrombotic events but one (pulmonary embolism in the LMWH group) were distal
venous thrombosis. Adverse events were most common in the intervention group than in the control group, RR 2.04 (95% CI 1.21
to 3.44). There were 66 episodes of adverse events. The number needed to harm was 20 for any adverse events.
Authors conclusions
This meta-analysis suggests that LMWH reduces the incidence of distal DVT diagnosed by sonogram. The clinical benefit of this is
uncertain. No strong evidence was found to conclude thromboprophylaxis is effective to prevent thromboembolic events and safe, in
people with unknown risk factors for thrombosis, undergoing knee arthroscopy.
PLAIN LANGUAGE SUMMARY

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy
Knee arthroscopy is a common, minimally invasive surgical procedure used both for diagnosis and treatment of knee conditions. It is
increasingly carried out in day surgery using various types of anaesthesia. Some people are at increased risk of developing deep vein
thrombosis (DVT) because of factors including a previous history, immobilization, smoking, obesity, varicose veins and increasing
age. Different approaches are available for preventing DVT (thromboprophylaxis), both mechanically and with drug medication. The
characteristic symptoms of DVT are limb pain and swelling (edema) but often there are no obvious signs or symptoms. DVT at or above
knee level (proximal) is associated with an increased risk of pulmonary embolism (which can be fatal) but isolated calf DVT (distal)
rarely causes symptoms and is asymptomatic. Arthroscopy patients are often young and soon become mobile again. The incidence of
DVT is reported to be from 0.6% when diagnosed clinically to 17.9% using the most sensitive imaging techniques (venography).
This review reports that low molecular weight heparin reduces the incidence of distal DVT diagnosed but the clinical benefits of this
are uncertain. The review authors identified four completed studies from three countries that randomly assigned a total of 527 adults
to low molecular weight heparin (LMWH) or no intervention or placebo. The mean age of participants ranged from 31 to 44 years
and nearly three quarters were male. The relative risk (RR) of thrombotic events was 0.16 (range 0.05 to 0.52). The number needed to
treat to prevent one thrombotic event was 17. All the blood clots were distal and were mainly diagnosed by sonogram. Adverse events
were most common in the intervention group. The most common complication was minor bleeding with a RR of 2.23 (range 0.99
to 4.99). The number needed to harm was 20. No completed studies were found that looked at mechanical devices such as graduated
elastic stockings or intermittent pneumatic compression, for patients immobilized in bed.
BACKGROUND
Deep venous thrombosis (DVT) occurs when a blood clot develops within the venous system, typically in the lower limbs. The
characteristic symptoms of DVT are limb pain and edema but
often there will be no obvious signs or symptoms (asymptomatic
DVT). The risk of developing DVT depends on multiple factors
including a previous history of DVT, immobilization, smoking,
obesity, varicose veins, increasing age, trauma, any hypercoagulable state (increased tendency for the blood to clot), and surgery.
Deep vein thrombosis increases the risk of pulmonary embolism
(PE) which can be fatal in 20% to 50% of cases, depending on the

population. After an episode of PE, 5% of patients have chronic
thromboembolic pulmonary hypertension (Hollerwerger 2000;
Kearon 2003).
Classically, DVT has been classified as proximal (thrombosis at or
above the popliteal vein) and distal, occurring below that level. The
distinction is important as while proximal DVT has been clearly
shown to increase the risk of pulmonary embolism (50% of people
with symptomatic proximal DVT will have PE in lung scans), the
clinical relevance of distal DVT is controversial in the literature.

The consensus is that isolated calf DVT is rarely symptomatic
(Kearon 2003). However, when DVT is both symptomatic and
untreated, 25 % of cases may extend to the proximal veins (Kearon
2003 ) and thus increase the incidence of post thrombotic syndrome in the affected leg, characterized by chronic persistent pain,
swelling, and other signs in the affected limb, increased risk of
recurrent venous thromboembolism, and venous ulcers (5% to
10%) (Kahn 2002), or result in PE.
OBJECTIVES
To assess the effectiveness and safety of interventions, mechanical
or pharmacological, or in combination, for thromboprophylaxis
in adult patients undergoing knee arthroscopy.
METHODS
Diagnosis of DVT may be difficult in the absence of symptoms

and consequently it is often under diagnosed (50 % of DVT cases
are asymptomatic) (Delis 2001). Venography (phlebography) is
the gold standard diagnostic method for DVT, but it is difficult
to justify its use as a screening method in a low-risk population,
due to its invasive character. Sonography (ultrasound) is used as a
diagnostic method, with the variation in accuracy dependent on
the technique used. Higher sensitivity is achieved using duplex
(71%) and higher specificity (98%) using compression ultrasound
alone (Goodacre 2005).
Criteria for considering studies for this review
Orthopedic surgery increases the risk of DVT. Knee arthroscopy

is a frequently performed surgical procedure in orthopedics, traditionally carried out on a young population, but the indication
for this procedure is now extending to older patients. Increasingly
arthroscopy is performed on an outpatient day-case basis with
early active/passive mobilization in the rehabilitation programs.
Arthroscopically-assisted surgery may be used for the treatment of
a variety of pathologies with different technical requirements for
example, washout, meniscectomy (removal of fibrocartilage from
the knee joint), anterior/posterior cruciate ligament reconstruction, lateral release, chondroplasty (repair of cartilage), articular
debridement (fibrosis, dead or infected material removal), synovial
resection, and tibial plateau fractures. Some of these procedures
may be considered minimally-invasive procedures; other procedures require the use of a tourniquet, extended surgical time, and
can cause more soft tissue and bone damage. General anesthesia,
subarachnoid blockade, femoral blockade, intraarticular or combined anesthesia, may be performed, each carrying independent
risks for DVT. The incidence of DVT in patients who undergo
venographically-screened, knee arthroscopy, is reported to be as
high as 17.9% (Demers 1998). Other studies report the incidence
of clinically diagnosed DVT as 0.6 % (Dahl 2000). If ultrasound
is used, the incidence is between 4.1% and 15.6% if ultrasound
is used (Michot 2002).
People over 18 years old undergoing knee arthroscopy. Trials of

arthroscopic-assisted osteosynthesis of tibial plateau fractures were
excluded.
Surgeons generally agree that thromboprophylaxis should be used

in moderate and high risk patients who undergo surgery. Graduated elastic stockings and intermittent pneumatic compression are
mechanical devices used to prevent DVT, the latter often used in
patients immobilized in bed. There are different opinions about
whether or not prophylaxis should be used in knee arthroscopy,
partly reflecting different perceptions of the underlying risk of
DVT.
Types of studies
Randomized clinical trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not (i.e. double blinded, single
blinded or unblinded).
Types of participants
Types of interventions
All type of interventions, whether mechanical or pharmacological,
single or in combination, used to prevent DVT in patients undergoing all types of knee arthroscopic interventions except arthroscopic-assisted osteosynthesis of tibial plateau fractures.
Types of outcome measures
Primary outcomes
Proximal and distal DVT events clinically, venographically

or sonographically diagnosed.
Pulmonary embolism diagnosed by V/Q lung scan, spiral
computed tomography (CT), or pulmonary angiography.
Death related to embolic events.
Secondary outcomes
Reported side/adverse effects.

Death.
Major bleeding (overt and requiring transfusion of red
blood cells or surgical interventions, and which may lead to
permanent disability).
Minor bleeding (did not meet the above major criteria for
intervention for example, hematoma, hemarthrosis,
thrombocytopenia (reduction of circulating platelets) of <
80000/mm3 or decrease > 50% of the initial count).
Search methods for identification of studies
Electronic searches
The Cochrane Peripheral Vascular Diseases (PVD) Group
searched their Specialized Register (last searched 25 October 2006)
and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched Issue 4, 2006) for all
publications describing (or which might describe) RCTs or CCTs
of mechanical or pharmacological interventions used to prevent
DVT in patients undergoing knee arthroscopy.
The PVD Groups Specialized Register contains citations of trials identified through electronic searches of MEDLINE (1966
to date); EMBASE (1980 to date); CINAHL (1982 to date);
and through handsearching journals and conference proceedings.
The full list of journals that have been handsearched, as well
as the search strategies used to search databases are described
in the editorial information about the Cochrane PVD Group
in The Cochrane Library http://www.mrw.interscience.wiley.com/
cochrane/clabout/articles/PVD/frame.html.
For details of the search strategy used to search CENTRAL see
(Appendix 1).
We also searched the following electronic databases according to
the methods described in the Cochrane Handbook for Systematic
Reviews of Interventions (Higgins 2005):
(1) MEDLINE from 1966 to October 2006 using the search terms
thrombotic [in all fields] AND arthro* [in all fields] AND prophy* [in all fields] OR preven* [in all fields], AND Hepar*[in all
fields] combined with the MEDLINE search strategies for randomized controlled trials suggested by the Cochrane Collaboration Handbook;
(2) EMBASE from 1980 to October 2006;
(3) Lilacs from 1988 to October 2006.
Searching other resources
In addition, we searched the reference lists of identified studies, and
articles and abstracts of international meetings of Orthopedics,
Hematology and Thrombosis journals from the year 1998 to 2004.
We contacted specialists known to be involved in phlebology and
interested in post thrombotic syndrome for details of unpublished
and ongoing trials. There were no restrictions on language.
Data collection and analysis
citations which seemed relevant to our review. Once identified, we

checked the citations and abstracts and, if the inclusion criteria
were met, we obtained the full text articles. Both authors decided
independently on trial inclusion using a standard form. The third
author (C Perrota) resolved any disagreements.
Quality assessment
J Ramos and G Badariotti evaluated each trial. The assessment of
quality included:
(1) The quality of allocation concealment categories:
Category A: adequate concealment
Category B: uncertain, indication of adequate
Category C: inadequate concealment
(2) Blinding: we evaluated if investigators, participants, outcome
assessor and data analysts were blinded to the treatment status. For
each one we commented yes, no, or not stated.
(3) Intention-to-treat analysis: we specified if the analysis was done
on an intention-to-treat basis (specifically reported by the authors,
or confirmed after reading the paper), or if the analysis was done
without intention-to-treat analysis, or if it was unclear in the article.
(4) Completeness of follow up: we checked the number of participants with data against the number of participants randomized,
expressed as a percentage overall, and in each intervention group.
Data extraction
J Ramos and G Badariotti independently extracted data. C Perrota
resolved any disagreements. When necessary, we sought additional
information from authors of relevant articles.
Data analysis
C Perrota entered the independently extracted data into RevMan.
We analyzed dichotomous outcomes as relative risks and recorded
their 95% confidence intervals. We combined the results using a
random-effects model to assess overall treatment effects. We used
a test of heterogeneity (chi-square) to assess potential differences
between trials. We explored the results from different methods
of outcome assessment, specifically the clinical diagnosis of DVT
compared with other methods. We planned other sensitivity analyses if there was significant heterogeneity. First we excluded individual studies one at time to assess whether any individual study
excessively influenced the analyses and then we excluded lower
quality studies without allocation concealment from the analyses
of primary outcomes.
Study Selection
Two authors (J Ramos and G Badariotti) independently screened
the initial results of all the databases and references lists to identify
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies; Characteristics of ongoing studies.
We identified six potentially eligible trials, of which four met the
review inclusion criteria (Canata 2003; Michot 2002; Roth 1995;
Wirth 2001). We excluded one trial (Marlovits 2004) that tested
the effects of extending the duration of LMWH prophylaxis (see
Characteristics of excluded studies table). The remaining trial by
Camporese et al (KANT Study) which compares two regimens of
Nadroparin with elastic stocking for seven days is described in the
Characteristics of ongoing studies table. We contacted the author
(last contact on December 2005) who confirmed that enrollment
was complete. Future updates of this review will discuss the results
of this trial.
Details of the four included trials are given in the Characteristics of included studies table. Three trials (Michot 2002; Roth
1995; Wirth 2001) were published as full reports; Canata 2003
is only available as an abstract for a conference poster. The four
trials were single centre studies conducted in three countries (Italy,
Switzerland, and two in Germany). All four included trials compared different regimens of thromboprophylaxis versus no intervention (control group). Overall, 527 predominantly male (average 70%) adults (trial mean ages where given, range from 31 to
44 years) were randomized between the two groups in the four
trials. The type of knee arthroscopy intervention performed varied
across studies: ACL reconstruction was done by the same surgeon
in Canata 2003; and ambulatory meniscus arthroscopy surgery
in Roth 1995. Michot 2002 included both diagnostic procedures
and a variety of therapeutic interventions, with ACL reconstruction. Over half of the participants in Wirth 2001 had a partial
meniscectomy; none of the rest had a ligamentous reconstruction.
History of previous DVT was an exclusion criterion and potential
risk factors were taken into account in both the Wirth 2001 and
Michot 2002 studies as well as use of tourniquet and type of
anesthesia. These topics were not as well established in Roth 1995
and Canata 2003.
The outcomes assessed were clinical suspicion of venous thrombosis or PE as the only outcome in one study (Canata 2003), clinical
suspicion of venous thrombosis or PE and DVT evaluated through
compression sonography were assessed in the other three (Michot
2002; Roth 1995; Wirth 2001).
All studies evaluated minor and major bleedings or other relevant
adverse events.
Risk of bias in included studies

Two studies had acceptable quality standards (Michot 2002; Wirth
2001). Both studies randomized participants although the method
of allocation was not reported. Blinding was intended in both studies however Wirth 2001 did not report how blinding was secured
in those who performed the sonograms. Inclusion and exclusion
criteria were clear as well as the analysis undertaken. Wirth 2001

excluded four patients in the control group from the intention-totreat analysis (not having had tourniquet or general anesthesia or
both) and reported to do so trying to gain homogeneity. Loss of
follow up was 8% in the intervention group (5/65) and 2% in the
control group (1/64) (Michot 2002) and 7% of patients withdraw
their informed consent in Wirth 2001.
Canata 2003 and Roth 1995 were the poorest quality trials. In both
studies allocation methods and how randomization was achieved
were not described. Inclusion and exclusion criteria were not described and intention-to-treat analysis was not done. Adverse event
definitions are not clear.
Effects of interventions
The relative risk (RR) of thrombotic events (all sites, diagnosed
both clinically and by ultrasound) was 0.16 (95% Confidence Interval (CI) 0.05 to 0.52). This RR was obtained through pooling data from the four studies with an overall 527 participants
(Canata 2003; Michot 2002; Roth 1995; Wirth 2001) evaluating
any LMWH versus no treatment before or after the procedure. In
these four studies all but one thrombotic events were distal DVT
(one event of pulmonary embolism in Michot 2002). Canata 2003
did not report any thrombotic events therefore its RR was not
estimable and has no effect on the calculated pooled RR.
Considering all the studies, there were three distal DVT in the
LMWH and one PE compared to 20 DVT in those who received
no treatment. We did a sensitivity analysis including only higher
quality studies and the RR did not change (RR 0.14; 95% CI 0.03
to 0.61) (Michot 2002; Wirth 2001). The number needed to treat
to prevent one thrombotic event was 17.
We intended to extract data only in those episodes of DVT that
were first noticed through clinical diagnosis. Only Wirth 2001
reported this outcome clearly and three patients out of 239 had
clinical symptoms of DVT (all in the control group) and the calculated RR was 0.15 (95% CI 0.01 to 2.85 P < 0.21).
There was only one episode of PE (in the treatment group) (Michot
2002).
Adverse events were most common in the intervention group than
in the control group with a RR 2.04 (95% CI 1.21 to 3.44). There
were 66 episodes of any adverse events, including allergies, one
patient with transient low levels of platelets, minor gastrointestinal
bleeding, two episodes of hemarthrosis in the intervened knee.
The most common complication was minor bleeding with a RR
of 2.23 (95% CI 1.99 to 4.99). The number needed to harm was
20.
We did not find heterogeneity in any of the comparisons made.
DISCUSSION
The RR of distal DVT (combining both clinically and sonogramdiagnosed DVT) comparing LMWH with no intervention for
knee arthroscopy was 0.16 (95% CI 0.05 to 0.52) and the RR of
any adverse events because of the intervention was RR 2.04 (95%
CI 1.21 to 3.44). The RR for clinically relevant thrombosis was
not statistically significant. All the thromboses were distal and the
majority were diagnosed by sonogram. There was no difference
between groups in relation to those DVT that were clinically relevant.
The incidence of DVT during arthroscopy varies from 3.1% to
17.9% in a meta-analysis by Ilahi et al (Ilahi 2005). However, the
question we are looking for an answer to is: what is the clinical
relevance of distal thrombosis diagnosed through sonogram? The
literature is not conclusive in this area. The incidence of PE in
distal asymptomatic DVT varies between 1.6% and 21% (Haas
1992; Kazmers 1999) and it is probably related to the patient risk
factors and type of thrombosis (Kearon 2003).
When performing arthroscopy, we are picturing a usually healthy
individual who will undergo a minor intervention. As in any other
medical intervention, the risk should outweigh the benefit. We
should weigh the risk of having a distal thrombosis with its unpredictable and quite low incidence outcomes against the minor complications caused by LMWH administration (although
some may argue that having a minor gastrointestinal bleeding or
hemarthrosis should not be called minor in these patients since
both will require intervention). It is difficult with only four studies
(and with only two good quality studies) to draw a conclusion. An
additional factor that should be taken into account is the cost of
treatment.
According to the results of a meta-analysis (Goodacre 2005), compression ultrasound seems to be appropriate as a screening method
in this low risk population where high specificity is required to
avoid false positive results.
The number needed to treat to benefit (NNTB) (17) relates to
asymptomatic DVT, and the number needed to harm (NNTH)
(20) is about a clinical event. Assuming a ratio of asymptomatic
distal DVT to clinically apparent DVT of 1:10 to 1:20, the NNTB
to prevent a clinical event would range from 170 to 340, with 8.5
to 17 times as frequent as harm occurring.
We conclude that the physician needs to discuss these benefits and
possible complications with the patient until new studies are performed. It is essential that future studies stratify patients according
to their risk factors, and also stratify arthroscopic procedures.
Since knee arthroscopy is a widely-used method and each center

may have its own guidelines on procedures, it would be helpful
to set up surveillance methods in each center to detect either adverse events or thrombotic events, with and without the use of
LMWH. Future epidemiological studies as well as clinical trials
will be needed to assess the natural history of non-clinical distal
DVT in these patients.
Studies should be carried out to evaluate the efficacy of mechanical
methods in knee arthroscopy for the prevention of thrombotic
events.
AUTHORS CONCLUSIONS
Implications for practice
The meta-analysis showed a reduction in the number of distal
thrombosis diagnosed through sonogram.
Although this review suggests that some benefit may be obtained
from prophylaxis, we considered only two studies to be of adequate methodological quality with small sample size, and poorly
defined or stratified in their arthroscopic intervention. No studies
on mechanical devices alone were found, other than the ongoing
combined protocol (Camporese 2003a).
No strong evidence was found to conclude thromboprophylaxis is
effective in preventing thromboembolic events in people undergoing knee arthroscopy with unknown risk factors for DVT.
Implications for research

Arthroscopic surgery includes different types of interventions with
different operation times, techniques, injury, recovery time, and
return to activity.
Future studies need to stratify patients according to their risk factors, and type of arthroscopic procedure. Surveillance studies will
be important to assess the detection of both adverse events and
thrombotic events, with and without the use of LMWH.
ACKNOWLEDGEMENTS
The authors would like to thank the contribution made to the
Plain Language Summary by Dr Janet Wale of the Consumer
Network.
REFERENCES
References to studies included in this review

Canata 2003 {published data only}
Canata GL, Chiey A. Prevention of venous
thromboembolism after ACL reconstruction: a prospective,
randomized study. ISAKOS (International Society of
Arthroscopy, Knee Surgery and Orthopaedic Sports
Medicine). 2003; Vol. Poster 712003.
Michot 2002 {published data only}
Michot M, Conen D, Holtz D, Erni D, Zumstein MD,
Ruflin GB, et al.Prevention of deep-vein thrombosis in
ambulatory arthroscopic knee surgery: A randomized
trial of prophylaxis with low-molecular weight heparin.
Arthroscopy 2002;18(3):25763.
Roth 1995 {published data only}
Roth P. Prophylaxis of deepvein thrombosis in
outpatients undergoing arthroscopic meniscus operation
[Thromboembolieprophylaxe bei ambulant durchgefrten
arthroskopischen Meniskusoperationen]. Orthopdische
Praxis 1995;5:3458.
Wirth 2001 {published data only}
Wirth T, Schneider B, Misselwitz F, Lomb M, Tyl H,
Egbring R, et al.Prevention of venous thromboembolism
after knee arthroscopy with low-molecular weight heparin
(Reviparin): Results of a randomized controlled trial.
Arthroscopy 2001;17(4):3939.
References to studies excluded from this review

Marlovits 2004 {published data only}
Marlovits S, Striessnig G, Schuster R, Stocker R, Luxl
M, Trattnig R, et al.A prospective, randomized, placebocontrolled study of extended-duration post-discharge
thromboprophylaxis with enoxaparin following arthroscopic
reconstruction of the anterior cruciate ligament. Blood
2004;104(11 Part 1):Abstract 1764.
References to ongoing studies

KANT Study {published data only}
Camporese G, Bernardi E, NTita K, Verlato F, Salmistraro
G, Cordova R, et al.Different thromboprophylaxis
approaches in patients undergoing knee arthroscopy
(KANT Study): A prospective randomized study. Journal
of Thrombosis & Haemostasis. 3 2005; Vol. 3, issue 1:
Abstract number: P1618.
Camporese G, Bernardi E, Prandoni P, Noventa F, Verlato
F, Simioni P, et al.Low-molecular-weight heparin versus
compression stockings for thromboprophylaxis after knee
arthroscopy: a randomized trial. Annals of Internal Medicine
2008;149(2):7382.
Camporese G, NTita K, Rossi F, Bernardi E, Verlato
F, Salmistraro G, et al.Different thromboprophylaxis
approaches in patients undergoing knee arthroscopy
(KANT study): interim report of prospective randomized
study. Journal of Thrombosis & Haemostasis. 1 2003; Vol.

1, issue Suppl 1:Abstract P1888.
Additional references
Dahl 2000
Dahl OE, Gudmunsen TE, Haukeland L. Late occurring
clinical deep vein thrombosis in joint-operated patients.
Acta Orthopaedica Scandinavaca 2000;71(1):4750.
Delis 2001
Delis KT, Hunt N, Strachan RK, Nicolaides AN. Incidence,
natural history and risk factors of deep vein thrombosis in
elective knee arthroscopy. Thrombosis & Haemostasis 2001;
86(3):81721.
Demers 1998
Demers C, Marcoux S, Ginsberg JS, Laroche F, Cloutier R,
Poulin J. Incidence of venographically proved deep vein
thrombosis after knee arthroscopy. Archives of Internal
Medicine 1998;158(1):4750.
Goodacre 2005
Steve Goodacre, Fiona Sampson, Steve Thomas, Edwin van
Beek, Alex Sutton. Systematic review and meta-analysis of
the diagnostic accuracy of ultrasonography for deep vein
thrombosis. BMC Medical Imaging 2005;5:6.
Haas 1992
Hass SB, Tribus CB, Insall JN, Becker MW, Windsor RE.
The significance of calf thrombi after total knee arthroplasty.
Journal of Bone & Joint Surgery - British Volume 1992;74(6):
799802.
Higgins 2005
Higgins JPT, Green S, editors. Cochrane Handbook for
Systematic Reviews of Interventions 4.2.5 [updated May
2005]. The Cochrane Library [database on CDROM]. The
Cochrane Collaboration, Chichester, UK: John Wiley &
Sons Ltd; 2005, issue 3.
Hollerwerger 2000
Hollerweger A, Macheiner P, Rettenbacher T, Gritzmann
N. Sonographic diagnosis of thrombosis of the calf muscle
veins and the risk of pulmonary embolism. Ultraschall in
der Medizin 2000;21(2):6672.
Ilahi 2005
Ilahi O, Reddy J, Ahmad I. Deep venous thrombosis after
knee arthroscopy: a meta-analysis. Artrhoscopy 2005;21(6):
72730.
Kahn 2002
Kahn SR, Ginsberg JS. The post-thrombotic syndrome:
current knowledge, controversies, and directions for future
research. Blood Reviews 2002;16(3):15565.
Kazmers 1999
Kazmers A, Groehn H, Meeker C. Acute calf vein
thrombosis: outcomes and implications. American Surgeon
1999;65(12):11247.
Kearon 2003
Kearon C. Natural history of venous thromboembolism.
Circulation 2003;107(23 Suppl 1):12230.
Indicates the major publication for the study
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Canata 2003
Methods
Study design: prospective, randomized controlled trial.

Method of randomization: not stated.
Concealment of allocation: not stated.
Intention to treat: no.
Participants
Country: Italy.
Setting: hospital.
Number: 36; 18 in each group.
Age: (mean) treatment group 29.6 years (range 22 to 59); control group 32.5 years (range 16 to 59)
Sex: treatment group 12 males, 6 females; control group 13 males, 5 females
Inclusion criteria: symptomatic ACL-deficient knees.
Exclusion criteria: none stated.
Interventions
Treatment: LMWH (enoxaparin sodium) sc daily (no dose specified)

Control: no intervention.
Duration: 6 days.
Outcomes
Compression color-coded sonography in case of clinically-suspected venous thrombosis; major (no cases)
and minor bleeding (2 in the intervention group and 3 in the control); range of motion
Notes
Surgery : ACL reconstruction performed by the same surgeon using a single technique and the same
rehabilitation protocol
Risk of bias
Item
Authors judgement
Description
Allocation concealment?
Unclear
B - Unclear
Michot 2002
Methods
Study design: prospective, single-blind, randomized controlled trial

Concealment of allocation: sealed envelope.
Losses to follow up: treatment group 5; control group 1.
Intention to treat: yes.
Participants
Country: Switzerland.
Setting: hospital outpatient department.
Number: 130; treatment group 66; control group 64.
Michot 2002
(Continued)
Age: (mean) treatment group 42.0 years (SD 14.7); control group 46.5 years (SD 13.2)
Inclusion criteria: patients requiring diagnostic or therapeutic arthoscopic knee surgery as outpatients;
aged 18 to 80 years
Exclusion criteria: inability or unwillingness to give written informed consent; past medical history of
DVT or PE, known deficiency of AT III, Protein C or Protein S; ongoing anti-thrombotic therapy, history
of GI bleeding in the previous 2 weeks; hypersensitivity to heparin; history of CVA in the previous 6
months; or severe renal or hepatic failure
All patients underwent bilateral compression ultrasonography of the legs the day before the operation.
Preoperative ultrasonography was inconclusive in 5 patients and revealed DVT in 2 patients
Included patients with independent risk factors for deep thrombosis
Interventions
Treatment: First dose of LMWH sc (2,500 IU anti-FXa deltaparin; Low Liquemin, Roche, Basel, Switzerland) 60 to 120 minutes before starting the procedure
Six hours after the end of the operation, a second, weight-adapted dose (2,500 IU if weight < 70 kg, 5,
000 if > 70 kg) was administered, and daily up to 30 days postoperatively
Control: no treatment.
Duration: 30 days.
Outcomes
Patients were seen on days 12 and 31 post operation for systematic questioning for symptoms of DVT and
PE, or bleeding complications and bilateral compression ultrasonography (US). If US was not conclusive,
venography was performed
Lower limb DVT was diagnosed in 10 patients in the control group (15.6%) and 1 in the intervention
group (1.5%)
All DVTs occurred in the operated leg.
Notes
Sample size was calculated at 400 patients was calculated to be the sample size but the trial was stopped
at 130 because it was decided that witholding LMWH was unethical. A wide variety of procedures was
carried out
Risk of bias
Item
Authors judgement
Description
Unclear
B - Unclear
Roth 1995
Methods
Study design: prospective, randomized controlled trial.

Exclusions post randomization: 22 due to non-compliance.
Intention to treat: no
Participants
Country: Germany.
Setting: hospital outpatient department.
Number: 122, (n = 61 in each group) (144 randomized, 22 excluded)
Age: Included patients more than 60 years old.
Sex: not stated.
Roth 1995
(Continued)
Inclusion criteria: patients undergoing ambulatory arthroscopic meniscus intervention, sinovectomy,

chondroplasty, loose-bodies resection
Included patients with independent risk factors for thrombosis
Interventions
Treatment: 0.3 ml sc fraxiparine 2 hours before the operation and self administered daily (except the first
two doses) for 4 days after surgery
Duration: 4 days.
Outcomes
Lower limb DVT and PE; bleeding; hematomas; allergic reactions were clinically evaluated 6 to 8 weeks
after surgery
DVT (6, one in the intervention group) were diagnosed, and venographically confirmed, all in the operated
limb. Venography indication was established after clinical assessment or ultrasonography. No PE was
detected (gammagraphy). No full weight bearing was allowed up to the 5th day
Five hematomas were found in the intervention group, and one in the control
Notes
Originally they were 144 patients but 22 were excluded due to non-compliance
Risk of bias
Item
Authors judgement
Description
Unclear
B - Unclear
Wirth 2001
Methods
Study design: prospective, randomized, controlled, blinded-outcome assessment trial

Exclusions pre-randomization: 23.
Withdrawals: 17 (withdrew informed consent).
Intention to treat: yes.
Participants
Country: Germany.
Setting: hospital.
Number: 239, treatment group 117; control group 122; 222 completed the trial, 111 in each group
Age: year SD, treatment group 37.6 13.0; control group 38.5 11.6
Inclusion criteria: elective knee arthroscopy.
Exclusion criteria: pregnant; < 18 years; history of DVT; or contraindication to contrast venography or
trial medication
Patients also screened for additional risk factors (obesity, nicotine abuse, oral contraceptives and family
history of thrombosis). If 3 or more present, patients were excluded
Interventions
Treatment: once daily injection of reviparin (1,750 anti Xa IU equivalent to 0.25 ml, sc) (Clivarin; Knoll
Deutchland GmbH, Ludwingshafen, Germany)
Duration: 7 to 10 days.
10
Wirth 2001
(Continued)
Outcomes
Primary: DVT diagnosed by compression color-coded ultrasonography and clinically symptomatic pulmonary embolism at days 7 to 10, or earlier in case of clinical symptoms
6 of 239 (2.5%), 5 (4.1%) in the control group, and 1 (0.85%) in the intervention group, had ultrasound
criteria for distal DVT. Four patients had minor bleeding complications (one in the control and three in
the intervention group)
4 patients (not having had tourniquet and/or general anesthesia) were excluded to achieve homogenity
Notes
Population size was calculated to be 196 patients in each group to detect a significant difference with an
alpha of 0.05 and a power of 0.80,
262 patients were eligible, 23 met exclusion criteria.
An interim analysis was planned after completion of 50% or 15 thromboembolic events, whichever
occured first
Risk of bias
Item
Authors judgement
Description
Unclear
B - Unclear
ACL: anterior cruciate ligament

AT III: antithrombin III
CVA: cerebrovascular accident
DVT: deep vein thrombosis
GI: gastrointestinal
LMWH: low molecular weight heparin
PE: pulmonary embolism
sc: subcutaneous
Characteristics of excluded studies [ordered by study ID]
Study
Reason for exclusion
Marlovits 2004
Evaluate the efficacy of an extended treatment with LMWH. Patients were randomly assigned to receive LMWH
until days 3 to 8 or until 20 days after surgery
As the goal of this trial was to assess the efficacy of an extended prophylaxis treatment, there is no comparison
with no treatment
LMWH: low molecular weight heparin
11
Characteristics of ongoing studies [ordered by study ID]

KANT Study
Trial name or title
KANT Study (Knee Arthroscopy Nadroparin Thromboprophylaxis)
Methods
Assessor-blinded, randomized controlled trial.
Participants
Consecutive patients undergoing knee arthroscopy for menisci lesions or for ACL or cartilage reconstruction
were eligible for inclusion
Interventions
Full length graduated compression stockings for 7 days (group A); or Nadroparin 0.4 ml sc once daily for 7
days (group B); or Nadroparin 0.4 ml sc once daily for 14 days (group C)
Outcomes
Thromboembolic events.
Starting date
Not available
Contact information
Notes
Enrollment is complete (a total of 2043 consecutive patients were considered, 282 were excluded and the
remaining 1761 patients wre assigned to treatment). Definitive results will be reported in 2008
ACL: anteior cruciate ligament

sc: subcutaneous
12
DATA AND ANALYSES
Comparison 1. Prophylactic treatment (all LMWH) versus no treatment
Outcome or subgroup title
No. of
studies
No. of
participants
527
Risk Ratio (M-H, Random, 95% CI)
0.16 [0.05, 0.52]
529
0.42 [0.06, 3.14]
4
4
4
527
527

Subtotals only
1.92 [0.97, 3.80]
2.23 [0.99, 4.99]
1 Participants with thrombotic

events (both clinical and
through diagnostic procedure)
2 Participants with clinical
thrombotic events
3 Participants with adverse events
3.1 All adverse events
3.2 Minor bleedings
Statistical method
Effect size
Analysis 1.1. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 1
Participants with thrombotic events (both clinical and through diagnostic procedure).
Review:
Comparison: 1 Prophylactic treatment (all LMWH) versus no treatment

Outcome: 1 Participants with thrombotic events (both clinical and through diagnostic procedure)
Study or subgroup
Treatment
Control
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Canata 2003
0/18
0/18
0.0 [ 0.0, 0.0 ]
Michot 2002
1/66
10/64
0.10 [ 0.01, 0.74 ]
Roth 1995
1/61
5/61
0.20 [ 0.02, 1.66 ]
Wirth 2001
1/117
5/122
0.21 [ 0.02, 1.76 ]
262
265
0.16 [ 0.05, 0.52 ]
Total (95% CI)

Total events: 3 (Treatment), 20 (Control)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.34, df = 2 (P = 0.84); I2 =0.0%

Test for overall effect: Z = 3.01 (P = 0.0026)
0.01
0.1
Favours treatment
10
100
Favours control
13
Participants with clinical thrombotic events.
Review:

Outcome: 2 Participants with clinical thrombotic events
Study or subgroup
Treatment
Control
Risk Ratio
MH,Random,95%
CI
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Canata 2003
0/18
0/18
0.0 [ 0.0, 0.0 ]
Michot 2002
0/66
0/64
0.0 [ 0.0, 0.0 ]
Roth 1995
1/61
1/63
1.03 [ 0.07, 16.15 ]
Wirth 2001
0/117
3/122
0.15 [ 0.01, 2.85 ]
262
267
0.42 [ 0.06, 3.14 ]
Total (95% CI)


0.001 0.01 0.1

Favours treatment
10 100 1000
Favours control
14
Participants with adverse events.
Review:

Outcome: 3 Participants with adverse events
Study or subgroup
Treatment
Control
Risk Ratio
MH,Random,95%
CI
Weight
Risk Ratio
MH,Random,95%
CI
n/N
n/N
Canata 2003
3/18
2/18
16.8 %
1.50 [ 0.28, 7.93 ]
Michot 2002
8/66
4/64
35.2 %
1.94 [ 0.61, 6.12 ]
Roth 1995
7/61
1/61
10.9 %
7.00 [ 0.89, 55.20 ]
Wirth 2001
7/117
5/122
37.1 %
1.46 [ 0.48, 4.47 ]
262
265
100.0 %
1.92 [ 0.97, 3.80 ]
1 All adverse events
Subtotal (95% CI)

2 Minor bleedings
Canata 2003
3/18
2/18
23.4 %
1.50 [ 0.28, 7.93 ]
Michot 2002
8/66
4/64
49.2 %
1.94 [ 0.61, 6.12 ]
Roth 1995
5/61
1/61
14.5 %
5.00 [ 0.60, 41.55 ]
Wirth 2001
3/117
1/122
12.9 %
3.13 [ 0.33, 29.65 ]
262
265
100.0 %
2.23 [ 0.99, 4.99 ]
Subtotal (95% CI)


0.01
0.1
Favours treatment
10
100
Favours control
15
APPENDICES
Appendix 1. CENTRAL search strategy
#1
MeSH descriptor Arthroscopy explode all trees
#2
arthroscop*
#3
knee near arthroscop*
#4
meniscectom*
#5
(#1 OR #2 OR #3 OR #4)
#6
MeSH descriptor Venous Thrombosis explode all trees
#7
MeSH descriptor Venous Thromboembolism explode all trees
#8
veno* or vein near thrombo*
#9
DVT
#10
MeSH descriptor Pulmonary Embolism, this term only
#11
pulmonary embol* or PE
#12
(#6 OR #7 OR #8 OR #9 OR #10 OR #11)
#13
(#5 AND #12)
FEEDBACK
Anticoagulant feedback, 14 February 2011
Summary
Feedback received on this review, and other reviews and protocols on anticoagulants, is available on the Cochrane Editorial Unit website
at http://www.editorial-unit.cochrane.org/anticoagulants-feedback.
16
WHATS NEW
Last assessed as up-to-date: 13 December 2006.
Date
Event
Description
14 February 2011
Amended
Link to anticoagulant feedback added
HISTORY
Protocol first published: Issue 2, 2005
Review first published: Issue 2, 2007
Date
Event
Description
5 August 2008
New citation required but conclusions have not changed Amendment to correct spelling error in title and labelling
of one of the graphs. Additional reference for ongoing
study (KANT Study) added
31 July 2008
Amended
Converted to new review format.
CONTRIBUTIONS OF AUTHORS
Jorge Ramos identified and selected potential trials, evaluated trial quality, and extracted data.
Gustavo Badariotti identified and selected potential trials, evaluated trial quality, and extracted data.
Carla Perrotta extracted data from selected trials, analyzed the results, and revised the text of the review.
Graciela Berestein contributed to the text of the review.
DECLARATIONS OF INTEREST
None known.
17
SOURCES OF SUPPORT
Internal sources
No sources of support supplied
External sources
Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK.
National Academy of Medicine, Centre for Epidemiologic Research, Cochrane Center, Argentina.
INDEX TERMS
Medical Subject Headings (MeSH)
Anticoagulants [ therapeutic use]; Arthroscopy [ adverse effects]; Heparin, Low-Molecular-Weight [ therapeutic use]; Knee Joint
[ surgery]; Randomized Controlled Trials as Topic; Stockings, Compression; Venous Thrombosis [ prevention & control]
MeSH check words

Adult; Humans
18

Interventions For Preventing Venous Thromboembolism in Adults Undergoing Knee Arthroscopy (Review)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Interventions For Preventing Venous Thromboembolism in Adults Undergoing Knee Arthroscopy (Review)

Uploaded by

Copyright:

Available Formats

Interventions for preventing venous thromboembolism in

adults undergoing knee arthroscopy (Review)

Interventions for preventing venous thromboembolism in

PLAIN LANGUAGE SUMMARY

(PE) which can be fatal in 20% to 50% of cases, depending on the

clinical relevance of distal DVT is controversial in the literature.

Diagnosis of DVT may be difficult in the absence of symptoms

Criteria for considering studies for this review

Orthopedic surgery increases the risk of DVT. Knee arthroscopy

People over 18 years old undergoing knee arthroscopy. Trials of

Surgeons generally agree that thromboprophylaxis should be used

Proximal and distal DVT events clinically, venographically

Reported side/adverse effects.

Search methods for identification of studies

Data collection and analysis

citations which seemed relevant to our review. Once identified, we

Risk of bias in included studies

criteria were clear as well as the analysis undertaken. Wirth 2001

Since knee arthroscopy is a widely-used method and each center

Implications for research

References to studies included in this review

References to studies excluded from this review

References to ongoing studies

study. Journal of Thrombosis & Haemostasis. 1 2003; Vol.

Indicates the major publication for the study

Characteristics of included studies [ordered by study ID]

Study design: prospective, randomized controlled trial.

Treatment: LMWH (enoxaparin sodium) sc daily (no dose specified)

Study design: prospective, single-blind, randomized controlled trial

Study design: prospective, randomized controlled trial.

Inclusion criteria: patients undergoing ambulatory arthroscopic meniscus intervention, sinovectomy,

Study design: prospective, randomized, controlled, blinded-outcome assessment trial

ACL: anterior cruciate ligament

Characteristics of excluded studies [ordered by study ID]

Reason for exclusion

LMWH: low molecular weight heparin

Characteristics of ongoing studies [ordered by study ID]

KANT Study (Knee Arthroscopy Nadroparin Thromboprophylaxis)

Assessor-blinded, randomized controlled trial.

ACL: anteior cruciate ligament

DATA AND ANALYSES

Comparison 1. Prophylactic treatment (all LMWH) versus no treatment

Outcome or subgroup title

Risk Ratio (M-H, Random, 95% CI)

0.16 [0.05, 0.52]

Risk Ratio (M-H, Random, 95% CI)

0.42 [0.06, 3.14]

Risk Ratio (M-H, Random, 95% CI)

1 Participants with thrombotic

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy

Comparison: 1 Prophylactic treatment (all LMWH) versus no treatment

0.0 [ 0.0, 0.0 ]

0.10 [ 0.01, 0.74 ]

0.20 [ 0.02, 1.66 ]

0.21 [ 0.02, 1.76 ]

0.16 [ 0.05, 0.52 ]

Total (95% CI)

Heterogeneity: Tau2 = 0.0; Chi2 = 0.34, df = 2 (P = 0.84); I2 =0.0%

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy

Comparison: 1 Prophylactic treatment (all LMWH) versus no treatment

0.0 [ 0.0, 0.0 ]

0.0 [ 0.0, 0.0 ]

1.03 [ 0.07, 16.15 ]