Systematic Review and Meta-Analysis Medicine ®

Ultrasound surveillance for deep venous

thrombosis and subsequent venous
thromboembolism in adults with trauma
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A systematic review and meta-analysis

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Abdulaziz M. Al-Sharydah, MDa,* , Mohammed S. Alshahrani, MDb, Khalid Maghrabi, MDc,

Wail Tashkandi, MDd,e, Marwa Amer, PhDf,g

Abstract
Background: Studies have shown routine ultrasound surveillance (RUSS) will facilitate deep vein thrombosis (DVT) detection in
patients with trauma and reduce the subsequent incidence of pulmonary embolism (PE); however, the findings were inconsistent.
In adults with trauma at a high risk of venous thromboembolism, this systematic review and meta-analysis compared RUSS
outcomes with those of “no RUSS.”
Methods: Three databases were screened for relevant articles from inception to October 18, 2021. Randomized controlled trials
(RCTs) and observational studies comparing RUSS with no RUSS were included. We used relative risks (RRs), odds ratios (ORs),
and mean differences to pool effect estimates for dichotomous and continuous outcomes. The cochrane risk of bias or the risk
of bias in non-randomized studies of interventions were used to assess bias risk. The grading of recommendations, assessment,
development, and evaluation framework assessed the certainty of the evidence.
Findings: Out of 1685 articles, 5 met the inclusion criteria (RCT: 1; observational studies: 4). Observational studies suggested
RUSS is associated with higher odds of DVT detection (OR, 4.87; 95% confidence interval [CI], 3.13–7.57; very low certainty).
Whereas higher risks of DVT were associated with RUSS in the RCT (distal DVT: RR, 15.48; 95% CI, 7.62–31.48; low certainty,
and proximal DVT: RR, 2.37; 95% CI, 1.04–5.39; very low certainty). Reduced odds of PE risk were observed with the RUSS (OR,
0.47; 95% CI, 0.24–0.91; very low certainty). Observational studies indicated that RUSS had an uncertain effect on mortality (OR,
0.46; 95% CI, 0.06–3.49). In the RCT, times to proximal and distal DVT diagnoses were shorter with RUSS (proximal DVT, mean
difference 2.25 days shorter [95% CI, 5.74–1.24]; distal DVT, mean differences 1.56 days shorter [95% CI, 4.22–1.12]; very low
certainty for both). Increasing bleeding risk was not linked to the RUSS group (RR, 1.24; 95% CI, 0.31–4.92).
Interpretation: The RUSS efficacy in adults with trauma at high risk for venous thromboembolism showed that it increases DVT
detection, decreases PE incidence, and shortens the time to DVT diagnosis, with an uncertain impact on mortality. The evidence
is low or very low in certainty because of bias, inconsistency, imprecision, and indirectness.
Abbreviations: aOR = adjusted odds ratio, CI = confidence interval, DVT = deep vein thrombosis, GRADE = grading of
recommendations, assessment, development, and evaluations, HR = hazard ratios, ICU = intensive-care-unit, LE = lower
extremity, MDs = mean differences, OR = odds ratio, PE = pulmonary embolism, RAP = risk assessment profile, RCT = randomized
controlled trial, ROB = risk of bias, RR = relative risk, RUSS = routine ultrasound surveillance, SRMA = systematic review and
meta-analysis, US = ultrasound, VTE = venous thromboembolism.
Keywords: proximal deep vein thrombosis, pulmonary embolism, trauma, ultrasound surveillance, venous thromboembolism

The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are
available from the corresponding author on reasonable request.
Supplemental Digital Content is available for this article.
a
Diagnostic and Interventional Radiology Department, King Fahd Hospital
of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi
Arabia, b Department of Emergency and Critical Care, King Fahd Hospital
of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi
Arabia, c Department of Critical Care Medicine, King Faisal Specialist Hospital
and Research Center, Riyadh, Saudi Arabia, d Department of Surgery, King
Abdulaziz University, Jeddah, Saudi Arabia, e Department of Critical Care,
Fakeeh Care Group, Jeddah, Saudi Arabia, f Medical/Critical Pharmacy
Division, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi
Arabia, g College of Medicine and Pharmacy, Alfaisal University, Riyadh, Saudi
Arabia.
*Correspondence: AbdulAziz M. Al-Sharydah, Diagnostic and Interventional
Radiology Department, King Fahd Hospital of the University, Imam Abdulrahman
Bin Faisal University, Khobar City, Eastern Province, Saudi Arabia (e-mail:
amsharydah@iau.edu.sa).
Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
How to cite this article: Al-Sharydah AM, Alshahrani MS, Maghrabi K, Tashkandi
W, Amer M. Ultrasound surveillance for deep venous thrombosis and subsequent
venous thromboembolism in adults with trauma: A systematic review and meta-
analysis. Medicine 2023;102:43(e35625).
Received: 28 October 2022 / Received in final form: 31 August 2023 / Accepted:
22 September 2023
http://dx.doi.org/10.1097/MD.0000000000035625

1
 Al-Sharydah et al. • Medicine (2023) 102:43Medicine
1. Introduction
Major trauma is a significant risk factor for deep vein throm-
bosis (DVT) and pulmonary embolism (PE). The incidence of
venous thromboembolism (VTE) varies among patients with
trauma. The estimated incidence of distal DVT is 58%, while
the estimated incidence of proximal DVT ranges from 14.7% to
27.3% (depending on the test used for diagnosing lower extrem-
ity DVT [LE DVT] as well as the mechanism of injury).[1,2] The
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mortality rates among patients with DVT are 3% to 9%.[3–6]
There is no consensus regarding the concept and practice of
ultrasound (US) examination for LE DVT.[2,7–11] US is a nonin-
vasive modality, and routine ultrasound surveillance (RUSS) can
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aid in the detection of asymptomatic or silent DVT. This in turn
can enable the initiation of optimal anticoagulant therapies to
preclude the progression of DVT to PE, thereby preventing the
occurrence of major VTE sequelae (such as recurrent VTE and
post-thrombotic syndrome).[2,3,12,13]
However, there are inconsistencies in the reported effects of
RUSS on the mortality and PE detection rates in patients with
DVT. Some observational studies have reported a reduction in
PE detection rates, while others have revealed no changes or
even an increase in PE detection and mortality rates.
In terms of clinical efficiency, some studies have shown the
clinical value and necessity of RUSS for patients with trauma
who are at a high risk of VTE development, especially those
with active bleeding (which prevents early initiation of phar-
macological VTE prophylaxis or leads to its frequent interrup-
tion) and those with orthopedic injuries and fixation devices
(which prevent initiation of mechanical prophylaxis).[2,9,10,14–16]
The utility and cost-effectiveness of LE US-based screening pro-
tocols for patients with trauma differ among trauma centers
and remain controversial, particularly in terms of the eligible
patients, screening frequency, and whether RUSS influences
clinically important VTE outcomes.[3,17–19] Thus, this systematic
review and meta-analysis (SRMA) was conducted as part of a
larger clinical practice guideline evaluating VTE prophylaxis in
trauma patients that was issued recently by the Saudi Critical
Care Society[20] and endorsed by the Scandinavian Society of
Anesthesiology and Intensive Care Medicine.[21] The essential
notion behind conducting this SRMA was to provide the best
available evidence tackling if we should recommend versus not
to recommend a RUSS in at-risk trauma patients who are not
candidates for pharmacological VTE prophylaxis. Despite the
available intuitive evidence, the impact of RUSS on preventing
the propagation of DVT into PE or fatal PE appears to be incon-
sistent, and the frequency of recommended RUSS is contradic-
tory. These intuitions neither applied to ambulating or low-risk
trauma patients nor patients with signs or symptoms suggestive
of DVT in whom RUSS is indicated.
2. Methods
We developed a predefined protocol for the present SRMA
on October 27, 2021 (Supplemental Digital Content File 1-
Predefined Protocol, http://links.lww.com/MD/K319). This
SRMA has been reported in accordance with the “Preferred
Reporting Items for Systematic Reviews and Meta-analyses
(PRISMA)” (Supplemental Digital Content File 2- PRISMA
checklist, http://links.lww.com/MD/K320), and the “Meta-
analysis of Observational Studies in Epidemiology (MOOSE)”
guidelines (Supplemental Digital Content File 3- MOOSE
Checklist, http://links.lww.com/MD/K321).[22,23]
2.1. Article selection and participants
We included randomized controlled trials (RCTs), observa-
tional studies, and cohort studies that used adjusted analyses
to compare the outcomes of LE RUSS (≥1 screening) between
adult patients with trauma (age >16 years) who underwent
2
the assessment and those who did not undergo the assessment.
We excluded case reports, conference abstracts or proceedings,
duplicate publications, pediatric cohort studies, editorials, sur-
veys, non-comparative studies, and studies involving patients
with no trauma.
2.2. Interventions and controls
LE RUSS was performed at a certain frequency to facilitate the
detection of DVT and prevent complications (such as phleg-
masia, PE, and post-thrombotic syndrome) in adults at a high
risk of VTE after a severe injury. The control group included
patients who did not undergo RUSS; in such patients, the stan-
dard of care comprised a duplex US examination that was
performed at the discretion of the treating physician if they
suspected DVT.
2.3. Outcome measures
The outcomes were divided into primary/critical and second-
ary/non-critical outcomes. The critical outcomes comprised the
rates of in-hospital and 90-day mortality; rates of in-hospital
and 90-day proximal DVT (i.e., DVT above the knee) and distal
DVT; rates of in-hospital and 90-day distal DVT progression;
rates of in-hospital and 90-day PE; rates of fatal PE; and safety
outcomes (Supplemental Digital Content Table 1- Outcome
Definitions, http://links.lww.com/MD/K323). The non-critical
outcomes comprised the time to VTE diagnosis (including times
to distal DVT, proximal DVT, and PE diagnoses), durations of
in-hospital stay and intensive-care-unit (ICU) stay, and ventila-
tor days.
2.4. Search methods
We performed a comprehensive search of Medline, Embase, and
the Cochrane Central Register of Controlled Trials databases
from inception to October 18, 2021. A medical librarian was
assigned to design the search strategy. Retrieval was limited to
English literature. Search results were imported into a reference
management software (EndNote version 20, New York), dupli-
cates were removed, and imported into Covidence Melbourne,
Australia.[24] Duplicates between Medline and Embase records
were removed using Ovid default duplicate detection, while
any additional duplicates were removed using EndNote and
Covidence. The keywords were chosen based on predefined
terms and reviewing the Medical Subject Headings terms of arti-
cles. We included the following keyword search terms: VTE, PE,
proximal DVT, distal DVT, RUSS, and trauma (Supplemental
Digital Content File 4- Search Strategy, http://links.lww.com/
MD/K322). Additionally, we manually searched all relevant nar-
rative reviews’ reference lists in cases of pertinent papers.
2.5. Data abstraction
Two reviewers (A.A. and M.A.) screened all citations inde-
pendently and in duplicate in 2 stages (first titles and abstracts
followed by full texts) to identify eligible studies. A citation
identified as potentially eligible by either reviewer in the first
stage advanced to the second stage. In the second stage, dis-
agreements were resolved by discussion or a third person (W.T.)
to identify reasons for exclusion. Data extraction was per-
formed by 2 reviewers (A.A. and M.A.) who used standardized
forms for data extraction in Covidence (Supplemental Digital
Content Table 2- Abstraction Sheet, http://links.lww.com/MD/
K324). Any disagreement was analyzed and resolved by discus-
sion, consensus, and when necessary, consultation with a third
reviewer (W.T.). W.T. and K.M. identified any additional stud-
ies not identified by the search strategy. The purpose of data
abstraction was to obtain the study population, injury types, US
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frequency, VTE prophylaxis types (mechanical and pharmaco-
logical), and outcome data.
2.6. Risk of bias assessment and grading of
recommendations, assessment, development, and
evaluations (GRADE) profile
We assessed the risk of bias (ROB) independently (A.A. and
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M.A.) and in duplicate for each study using a Cochrane tool
for RCTs that classified ROB as “low,” “probably low,” “prob-
ably high,” or “high” for each of the following items[25]: ran-
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domization and sequence generation, concealment, blindness,
analytical methods, allocation, incomplete data, selective out-
come reporting, and other ROB. We assessed the ROB for
observational studies using the risk of bias in non-randomized
studies of interventions tool that classified ROB as “low risk,”
“moderate risk,” “serious risk,” and “critical risk” for each of
the following domains[26]: bias based on confounding, enroll-
ing participants into the study, sorting interventions, deviations
from intended interventions, incomplete data, measuring out-
comes, and including reported result. Investigator with expertise
in the grading of recommendations, assessment, development,
and evaluations (GRADE) approach assessed the overall cer-
tainty in the pooled estimates for each outcome.[27] Certainty
assessment are based on several factors, including study design,
ROB, consistency, directness, precision, and publication bias. In
accordance with recommendations for interventional reviews,
pooled data from RCTs started as high certainty and pooled
data from observational studies as low certainty. Quality of
evidence was categorized as high, moderate, low, and very low
and we created GRADE evidence profile using GRADEpro
Guideline Development Tool v3.6.1 (McMaster University and
Evidence Prime, 2022). In cases of inconsistency between RCT
results and observational data, we highlighted the findings with
a higher certainty.
2.7. Statistical analysis
We performed the meta-analyses using the inverse variance
weighting and Review Manager v5.3 (Cochrane Collaboration,
Oxford, United Kingdom).[28] We specified no prior subgroup
analyses. Paralleling published guidance and due to method-
ological heterogeneity, RCTs and observational studies were
pooled separately.[29] Studies with sufficient clinical and method-
ological commonality were combined into meta-analyses. Forest
plots were utilized to represent qualitative RCTs and quantita-
tive synthesis of observational studies, displaying meta-analysis
and analyzing the results in different subgroups among stud-
ies.[30] We calculated relative risks (RRs) and mean differences
(MDs) for dichotomous and continuous outcomes, respec-
tively, with corresponding 95% confidence intervals (CIs). For
continuous outcomes, we assumed a normal distribution (i.e.,
median = mean) and converted interquartile range to standard
deviation using the methods suggested by the Cochrane hand-
book for systematic reviews of interventions and the methods
described by Wan et al[27,31] We considered both the random
and fixed effects models considering study heterogeneity and
the risk of small studies effects (fixed-effect model was consid-
ered when the number of studies was <3). Clinical and meth-
odological heterogeneity across the studies were evaluated by
examining the patients’ data, baseline data, interventions, and
outcomes to determine sufficient similarities between studies.
Additionally, we used the I2 statistics to assess the heterogeneity
(I2 of 30%–60% and >60% as moderate and substantial het-
erogeneity, respectively), and chi squared test for homogeneity
using visual inspection of forest plots. We considered the magni-
tude and direction of heterogeneity to rate down the certainty in
evidence for inconsistencies. We performed sensitivity analysis
for observational studies with low-to-moderate ROB (excluding
3
high ROB studies). For each outcome, we performed additional
sensitivity analysis for observational studies of adjusted odds
ratios (ORs) and hazard ratios (HRs) using the random-effects
method for estimation of between study variances. In this anal-
ysis, we excluded studies that did not provide ORs or HRs with
corresponding CIs and which were adjusted for confounding by
accounting for at least one of the following: type of pharmaco-
logical thromboprophylaxis received (unfractionated heparin/
low-molecular-weight heparin), mechanical VTE prophylaxis
use, injury severity score, abbreviated injury scale, acute phys-
iology and chronic health evaluation (APACHE) II score, and
the presence of femoral CVC at baseline. In accordance with
Cochrane guidance, we combined studies with dichotomous
outcome data (OR) and time-to-event data (HR) when the event
rate was low (<10%).[29] We present results as pooled adjusted
OR (aORs) with 95% CIs (most conservative estimates that are
available) as opposed to pooling events and totals.
3. Results
3.1. Search results and study characteristics
Of the 1685 citations (Fig. 1) identified, we retrieved 20 full
texts and reviewed 5 controlled studies (4 observational stud-
ies[3–5,32] and an RCT[33]) (Table 1 and Supplemental Digital
Content Table 3, http://links.lww.com/MD/K325- Details of the
Trials). Of the observational studies, Arabi et al[32] performed a
pre- planned sub-study of the Prevention of Recurrent Venous
Thromboembolism (PREVENT) trial and included patients
with and without trauma.[32] The included studies were predom-
inantly large observational cohorts[3–5,32] and an RCT[33] (from
the United States); an exception was the PREVENT multicenter
study.[32] Two studies[3,33] included adults with trauma and mod-
erate- or high-risk for VTE using a risk assessment profile (RAP)
score ≥5 in a study[33] or >10 in another study.[3]
Majority of the studies predominantly included patients
with blunt trauma as well as penetrating injuries, while 1
study included patients with traumatic brain and isolated
spinal cord injuries.[3] Five studies reported the use of phar-
macological prophylaxis (low molecular weight heparin
and unfractionated heparin in 5 and 4 studies, respectively).
Pharmacological prophylaxis was typically initiated within
23 hours in an RCT[33] and approximately 48 to 72 hours of
admission in 3 observational studies[3,5]; and co-administra-
tion of mechanical prophylaxis in 3 other studies.[3,5,32] The
exclusion criteria common in the included studies were hyper-
coagulable state (e.g., presence of antiphospholipid syndrome,
factor V Leiden, protein C and S deficiencies, and active can-
cer) and a history of VTE within 6 months. Importantly, dis-
tinction between proximal and distal LE DVTs as outcome
measures was reported in 2 studies.[32,33] RUSS screenings were
reported with varying frequencies. In the RCT, the RUSS pro-
tocol during hospitalization included serial LE doppler US on
the 1st, 3rd, and 7th days followed by weekly RUSS until dis-
charge.[33] In the observational studies, 1 study[3] performed
RUSS weekly, while another[5] performed RUSS twice weekly
for patients in the ICU and once weekly for those admitted
in the general ward. In the study by Arabi et al,[32] RUSS was
performed within the first 48 hours and twice weekly subse-
quently until discharge.[32] The no-RUSS group was screened
based on clinical suspicion. Another study[4] did not specify
the timing of RUSS in patients with asymptomatic trauma or
the criteria in the no-RUSS group; however, the study specified
that patients at high risk of DVT were screened.
3.2. Risk of bias
The Cochrane ROB Tool for RCTs revealed that the included
RCT had a low ROB.[33] The residual bias was attributed to
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Figure 1. “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” flow diagram depicting the updated search strategy.
the blinding domain of the participants, a lack of blinding
of the clinicians responsible for ordering the serial US scans,
and an unclear ROB in the blinding domain of the outcome
assessors. The risk of bias in non-randomized studies of inter-
ventions tool revealed that 2 observational studies had a mod-
erate ROB that was attributed to confounding arising from
lack of adjustment for serious baseline differences. In one of
these studies, most patients who underwent US surveillance
required surgical interventions and sustained vascular and
spinal cord injuries.[3] In the other study, the pharmacologi-
cal prophylaxis differed significantly among the participating
centers.[5] In 3 observational studies,[3,5,32] bias was attributed
to missing data, insufficient reporting of the doses adminis-
tered for pharmacological prophylaxis, and differences in
mechanical prophylactic co-interventions. (Supplemental
Digital Content Fig. 1- Risk of Bias Assessment, http://links.
lww.com/MD/K315).
3.3. Outcomes
Figures 2 to 5 and Table 2 present the outcomes in the form
of forest plots (qualitative pooled data from RCTs and quan-
titative synthesis of pooled data from observational studies),
and GRADE assessments, respectively. (Supplemental Digital
Content Table 4- GRADE Certainty Assessments, http://
links.lww.com/MD/K326) Further details are presented in
4
(Supplemental Digital Content Fig. 2- Sensitivity Analysis,
http://links.lww.com/MD/K316).
3.4. DVT
The RUSS group in the included RCT (N = 1989) was associ-
ated with increased rates of in-hospital distal DVT (RR, 15.48;
95% CI, 7.62 − 31.48; low certainty) and in-hospital proxi-
mal DVT (RR, 2.37; 95% CI, 1.04 − 5.39; very low certainty).
However, there were no significant differences in the rates
of 90-day proximal and distal DVTs between the RUSS and
no-RUSS groups.[33] The likelihood of in-hospital distal DVT
progression was higher in the RUSS group than in the no-RUSS
group (RR, 3; 95% CI, 0.31–28.76; very low certainty; Fig. 2).
Evidence from observational studies (four studies, N = 10,642)
suggested higher odds of DVT detection using RUSS (OR, 4.87;
95% CI, 3.13–7.57; very low certainty).[3–5,33] Similarly, pooled
estimates of aORs from 2 observational studies also revealed
that RUSS was potentially associated with higher odds of DVT
detection (aOR, 4.49; 95% CI, 2.76–7.31; very low certainty;
Fig. 3).[5,32] After excluding a study with a high ROB,[4] sensi-
tivity analyses of studies with a low-to-moderate ROB revealed
similar trends (OR, 4.69; 95% CI, 2.98–7.38; Supplemental
Digital Content Fig. 2- Sensitivity Analysis, http://links.lww.
com/MD/K316).
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Table 1
Characteristics of included studies.
Pharmacological VTE
Study Sample Mean/median age (yr) prophylaxis and mean Mechanical VTE
Study Country design Data source Patient population size ± SD ISS ± SD Screening US initiation time Prophylaxis

Kay et al USA RCT Single center ⃞ Adults w/t trauma 1989 62 ± 20.1 14 ± 9.7 ⃞ RUSS group: serial LE ⃞ 7 5% LWMH NR
(2021)[33] (moderate- or high- US on 1st, 3rd, and 7th ⃞ 2 0% UFH
risk defined by a RAP in hospital days and ⃞ 2 %–3% DOACs
score of ≥5) thereafter weekly till ⃞M  IT was about 23 h in
⃞ 97% had blunt trauma discharge. both groups
⃞ No US for upper extrem-
ities and neck
⃞ Non-RUSS group: at
the discretion of trauma
provider based on clini-
cal suspicion of VTE
Allen CJ USA Observational Single center ⃞ A symptomatic trauma 402 47 ± 19 6.32 ± 1.87 ⃞ RUSS group: Bilateral ⃞ A bout 9%–10% SCD was used if not
et al study patients (as high risk LE US weekly from the did not receive any prohibited by plaster
(2016)[3] for VTE RAP >10) ankle to the inguinal PVTEPx immobilizer or external
⃞ 70%–80% had blunt ligaments. ⃞ 9 0% received PVTEPx fixators
trauma ⃞ Proximal venous system ⃞ 4 0%–50% UFH
⃞ 40 % had TBI (above or including ⃞ 7%–16% Enox.
the popliteal vein), Calf ⃞M  IT around 3rd
veins, Neck, and UE hospital day.

5
Haut et al USA Observational Single center ⃞ Before and after study
(2007)[4] study (i.e., 2 phases before
(1995–1997), and
after (1999–2005)
⃞ RUSS group are less
injured and less likely
to have penetrating
injuries
Shackford USA Observational Two centers ⃞ Comparison between 2
et al study hospitals (i.e., Scripps
(2016)[5] Mercy hospital = RUSS
group and Christiana
Care hospital = non-
RUSS group) w/t
⃞ Overall VTE risk
between the 2 groups
based on ISS was
similar.
⃞ Included neurotrauma
patients TBI and spinal
cord injury
were not included.
⃞ non-RUSS: If symptoms
indicated by clinical
suspicion of DVT
7559 ⃞ 32.1 in the before ⃞ 11.7 in the before ⃞ RUSS group (after-phase
phase patients phase patients patients), for asymptom-
⃞ 33.6 in the af- ⃞ 8.9 in the after-phase atic trauma patients at
ter-phase patients patients high risk for DVT.
⃞ non-RUSS (be-
fore-phase patients)
1226 ⃞ 49.5 ± 22.4 (n = 772) 10 in both centers. ⃞ RUSS group (Scripps
Scripps Mercy Mercy), LE US twice
⃞ 57.4 ± 23.7 (n = 454) weekly for patients
Christiana Care admitted to ICU, and
weekly for patients
admitted to the trauma
floor
⃞ non-RUSS (Christiana
Care), LE US only for
symptomatic patients
⃞ E nox. (dosed 30 mg NR
twice daily).
⃞N  R per group
⃞N  R MIT
⃞ S ignificantly differ ⃞ S ignificantly differ
between groups between groups
⃞ 5 7% PVTEPx in RUSS ⃞ 9 4% used IPC in RUSS
⃞ 8 0% PVTEPx in non- patients
RUSS ⃞ 6 0% used IPC in non-
⃞ P VTEPx held for 48 h RUSS patients
in RUSS and for 72 h
in non-RUSS patients
w/t intracranial
hemorrhage
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(Continued)
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3.5. Pulmonary embolism (PE)

DOACs = direct oral anticoagulants, DVT = deep vein thrombosis, Enox = enoxaparin sodium, ICU = intensive-care-unit, IPC = intermittent pneumatic compression, ISS = injury severity score, LE = lower extremity, LWMH = low-molecular-weight heparin, MIT = mean initiation time,
⃞ 3 0% used IPC in non-

Non-RUSS = no routine US surveillance, NR = not reported, NR = not reported, PVTEPx = pharmacological VTE prophylaxis, RAP = risk assessment profile, RCT = randomized controlled trial, RUSS = routine US surveillance, SCD = sequential compression device, SD = standard
PE events were grouped by detection time (in the hospital
Mechanical VTE

⃞ 5 4.6% used IPC in

Prophylaxis
or within 90 days of follow-up). Kay et al[33] demonstrated
a significantly lower rate of in-hospital PE detection in the

RUSS group

RUSS group
RUSS group than in the no-RUSS group (RR, 0.11; 95%
CI, 0.01–0.87; very low certainty, Fig. 4).[33] After excluding
the high ROB study,[4] sensitivity analysis of 3 observational
studies with a low-to-moderate ROB (N = 3692) reduced
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heterogeneity and revealed a reduction in the PE detection

prophylaxis and mean
Pharmacological VTE

rates with RUSS (OR, 0.47; 95% CI, 0.24–0.9; I2 = 0; very

⃞ P VTEPx was equal

⃞ 35%–40% LMWH
initiation time

low certainty).[3,5,33] Furthermore, pooled estimates of aORs

⃞ 60%–65% UFH
between group

from 2 observational studies revealed that RUSS was poten-

wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 10/30/2023

tially associated with lower odds of PE detection (aOR, 0.65;

95% CI, 0.28–1.52; very low certainty); however, the 95%
CI could not exclude an absence of differences or a clinically
important benefit. These results are limited by indirectness
and serious imprecision.[5,32]
and neck US within 48 h
proximal, distal, LE, UE,

⃞ Non-RUSS, requested
Screening US

then twice weekly

based on clinical
⃞ RUSS group, all

3.6. Mortality
In the included RCT, no difference was observed between the
suspicion.

in-hospital mortality (RR, 0.73; 95% CI, 0.44–1.22; very low

certainty) and 90-day mortality (RR, 0.83; 95% CI, 0.59–1.18;
deviation, TBI = traumatic brain injury, UE = upper extremity, UFH = unfractionated heparin, US = ultrasound, USA = United States of America, VTE = venous thromboembolism, w/t = with.

low certainty) in both the RUSS and no-RUSS groups. Similarly,

the effects of RUSS on mortality were uncertain in 2 observa-
tional studies (pooled OR, 0.46; 95% CI, 0.06–3.49; very low
certainty).[3,4] After excluding the high ROB study,[4] sensitivity
ISS ± SD

analysis of studies with a low-to-moderate ROB revealed iden-

tical trends in the invariable results. In one observational study,
analysis using a Cox proportional hazards model revealed that
compared with the no-RUSS group, the RUSS group was associ-
ated with lower 90-day adjusted mortality and 90-day adjusted
NR

ICU mortality (HR, 0.51; 95% CI, 0.51–0.99; very low cer-
54.1 ± 19.6 (N = 383)
Mean/median age (yr)

tainty); however, no intergroup differences were observed in

2065 ⃞ 58.6 ± 20.6 RUSS
group (N = 1682)

the in-hospital mortality (HR, 0.78; 95% CI, 0.59–1.02; very

low certainty; Fig. 5).[32] (Supplemental Digital Content Fig. 3-
± SD

⃞ Non-RUSS

Sensitivity analysis for low-moderate ROB studies, http://links.

lww.com/MD/K317).

3.7. Time to VTE diagnosis

Sample
size

In the included RCT, times to both proximal DVT diagnosis (MD,

2.25 days shorter; 95% CI, 5.74–1.24; very low certainty) and
distal DVT diagnosis (MD, 1.56 days shorter; 95% CI, 4.22–
RUSS group and 7.1%
⃞ From all PREVENT trial

1.12; very low certainty) were shorter in the RUSS group than in
⃞ Downgraded for indi-
patients, only trauma

this sub-study (8.5%

Patient population

patients included in

rectness by 1 point

the no-RUSS group. Furthermore, the average time to proximal

non-RUSS group)

DVT development was 90 days in the RUSS group and 8 days in

the no-RUSS group.[33] The average time to distal DVT develop-
ment was 124 days in the RUSS group and 8 days in the no-RUSS
group. One observational study reported on the time of VTE
diagnosis and revealed that RUSS was associated with an earlier
diagnosis of DVT (MD, 14 days shorter; 95% CI, 14.53–13.47)
Data source

and PE (MD, 10 days shorter; 95% CI, 12.04–8.64).

Observational Ten centers

3.8. Bleeding outcomes associated with unnecessary

administration of therapeutic doses of anticoagulants in
design
Study

the treatment of clinically silent DVT

study

For distal DVT, 2 of 8 patients (25.0%) in the no-RUSS group

and 11 of 124 patients (8.9%) in the RUSS group received full
doses of anticoagulants (P = .18). For proximal DVT, 4 of 8
Country

of Saudi
Arabia

patients (50.0%) in the no-RUSS group and 14 of 19 patients

Kingdom

(73.7%) in the RUSS group received full doses of anticoagulants

(P = .38). No intergroup differences were observed in the major
(Continued)

bleeding rate and no association of increased bleeding risk was

Table 1

PREVENT
(2020)[32]

study of

observed with RUSS group (RR, 1.24; 95% CI, 0.31–4.92;

Arabi et al

Sub-

(Supplemental Digital Content Fig. 4, http://links.lww.com/MD/

trial
Study

K318- Forest plot for major bleeding).[33]

6
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Figure 2. Proximal and distal deep vein thromboses: forest plot for randomized controlled trials.
4. Discussion
4.1. Main findings
This SRMA summarized the best available evidence on the
role of RUSS in adult patients with trauma and its effects on
the outcomes of this population. RUSS may result in improved
DVT detection rates, fewer cases of PE, shorter times to DVT
diagnosis, and uncertain effects on mortality. Pending further
information, very-low-certainty data support the use of rou-
tine bilateral LE US for screening asymptomatic DVT in adults
with trauma who are at a high risk of VTE but are not candi-
dates for pharmacological VTE prophylaxis.[9,10,14–16] A possi-
ble explanation for this is that the diagnosis and treatment of
DVT reduced the following: need for additional investigations
for PE, progression of proximal DVT, and embolization of
7
clots (thereby preventing fatal PE). Early detection and diag-
nosis will enable initiation of appropriate therapies, such as
systemic anticoagulants or inferior vena cava filter placement
in patients whose conditions are contraindicated for systemic
anticoagulants. Concordantly, our results agree with these
reports and support using RUSS to diagnose silent DVT in
adults with trauma.
Diagnostic studies have revealed that LE DVT has an esti-
mated incidence of 10 to 90% in patients with head inju-
ries.[34,35] Most patients (86%) with trauma who underwent
RUSS weekly were diagnosed with LE DVT but were clinically
asymptomatic; this highlights the silent nature of LE DVT.[36]
Therefore, implementing RUSS can lower the incidence rates of
PE and the subsequent morbidity in and mortality of seriously
injured patients.[3] Furthermore, Kadyan et al[37] and Bandle
 Al-Sharydah et al. • Medicine (2023) 102:43Medicine

Table 2
Outcome GRADE assessments.
Outcome GRADE Studies (N) Pooled RR or OR (95% CI) P value I2 value Certainty

In-Hospital distal DVT- RCT 1 RCT[33] ⃞ RR 15.48 (7.62–31.48) Non-applicable Non-applicable ⨁⨁◯◯
Low
In-Hospital proximal DVT-RCT 1 RCT[33] ⃞ RR 2.37 (1.04–5.39) Non-applicable Non-applicable ⨁◯◯◯
Very low
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In-hospital, Distal DVT propagation-RCT 1 RCT[33] ⃞ RR 3.00 (0.31–28.76) Non-applicable Non-applicable ⨁◯◯◯
Very low
All DVT- observational 4 studies[3–5,32] ⃞ OR 4.87 (3.13–7.57) P < .00001 I2 = 0% ⨁◯◯◯
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 10/30/2023

Very low
All DVT- observational adjusted OR 2 Observational study[5,32] ⃞ Adjusted OR 4.49 (2.76–7.31) P < .00001 I2 = 0% ⨁◯◯◯
Very low
In-hospital PE -RCT 1 RCT[33] ⃞ RR 0.11 (0.01–0.87) Non-applicable Non-applicable ⨁◯◯◯
Very low
PE observational studies 4 Observational studies ⃞ OR 0.69 (0.26–1.85) P = .46 I2 = 52% ⨁◯◯◯
Very low
PE- observational adjusted OR 2 Observational study[5,32] ⃞ Adjusted OR 0.65 (0.28–1.52) P = .32 I2 = 0% ⨁◯◯◯
Very low
Time to distal DVT Dx -RCT 1 RCT[33] ⃞ MD 1.55 lower (4.22 lower to 1.12 Non-applicable Non-applicable ⨁◯◯◯
higher) Very low
Time to proximal DVT Dx -RCT 1 RCT[33] ⃞ MD 2.25 lower (5.74 lower to 1.24 Non-applicable Non-applicable ⨁◯◯◯
higher) Very low
90-d mortality-RCT 1 RCT[33] ⃞ RR 0.83 (0.59–1.18) Non-applicable Non-applicable ⨁⨁◯◯
Low
In-hospital mortality-RCT 1 RCT[33] ⃞ RR 0.73 (0.44–1.22) Non-applicable Non-applicable ⨁◯◯◯
Very low
90-d mortality (PREVENT sub-study)* 1 Observational study[32] ⃞ HR 0.75 (0.57–0.99) Non-applicable Non-applicable ⨁◯◯◯
Very low
ICU mortality (PREVENT sub-study)* 1 Observational study[32] ⃞ HR 0.71 (0.51–0.99) Non-applicable Non-applicable ⨁◯◯◯
Very low
In hospital mortality (PREVENT sub-study)* 1 Observational study[32] ⃞ HR 0.78 (0.59–1.02) Non-applicable Non-applicable ⨁◯◯◯
Very low
DVT = deep vein thrombosis, GRADE = grading of recommendations, assessment, development, and evaluations, HR = hazard ratio, I2 value = test of heterogeneity, ICU = intensive-care-unit, MD = mean
differences, OR = odds ratio, PE = pulmonary embolism, P value = probability value, RCT = randomized controlled trial, RR = relative risk.
*Assessed with: Cox proportional hazards model.

et al[12] reported that unlike in patients with a low-to-moder-
ate risk of DVT, RUSS is both lifesaving and cost-effective in
patients with a spinal cord injury and in those who are at a high
risk of DVT after trauma.[12,37] Contrastingly, Cipolle et al[2]
failed to identify an association between RUSS and a reduction
in the incidence of PE. They concluded that the PE incidence
was more influenced by the patient compliance with the phar-
macological VTE prophylaxis protocol (i.e., administration of
un-fractionated subcutaneous heparin followed by conversion
to low-dose warfarin) than by RUSS. The authors emphasized
that adherence to a prophylactic pharmacological protocol was
more crucial than RUSS for preventing VTE sequelae.
Existing literature on the role of RUSS in patients with trauma
remains controversial owing to non-uniform findings regarding
the clinical application of RUSS and concerns of surveillance
bias.[3,15,17,19] Some healthcare agencies have linked the incidence
of in-hospital VTE with the quality of medical care provided and
have proposed that hospitals with higher rates of VTE should
face punitive diminutions in reimbursements.[4] Huat et al[4] imple-
mented a more aggressive RUSS protocol for DVT in patients
with trauma and reported a 10-fold increase in the DVT detection
rate, thereby demonstrating a significant surveillance bias. Pierce
et al[38] analyzed data from the National Trauma Data Bank and
identified a similar surveillance bias in hospitals across the United
States. Furthermore, a survey of 317 surgeons revealed wide vari-
ations in the individual opinions on the need for DVT screen-
ing among asymptomatic patients with trauma; 53%, 36%, and
11% agreed, disagreed, and neither agreed nor disagreed with the
screening, respectively. Furthermore, approximately 73% of the
responders in this survey thought that patients should be screened
early (i.e., within the first 6 days of admission). Moreover, approx-
imately 61% of the respondents thought that a duplex US exam-
ination should be performed every week. Approximately 60% of
the respondents worked at a trauma center that did not follow
published guidelines or protocols for duplex US-based screening
for DVT among asymptomatic patients with trauma.[2]
The clinical efficacy of RUSS for post-trauma VTE prophy-
laxis is still debated. Some guidelines recommend RUSS to detect
asymptomatic DVT in trauma patients at high risk of VTE, but
they do not agree on the associated risk or the effect of RUSS on
PE rates.[39–41] They even discourage reporting the rate of DVT
as a hospital outcome since RUSS would essentially elevate
it.[40] In patients with low-risk of DVT, many studies argue that
RUSS does not decrease the rate of PE or fatal PE, may cause
false positives, and is costly for this population.[40,42] Although
most studies use the Greenfield RAP score >10 to identify risk
of VTE and thereby, select patients for RUSS, others employ the
abbreviated injury scale score >3 as a risk factor for VTE in
patients with trauma.[12,40,42] A brief overview of current opinion
of major surgical societies in the management of trauma-related
VTE can be found in (Supplemental Digital Content Table 5,
http://links.lww.com/MD/K327- Recommendations from major
societies on post-trauma thromboprophylaxis).
Previous cost-effective analyses have focused on the financial
costs of patient care.[2,9] Studies that oppose RUSS have sug-
gested that its associated costs are prohibitive,[8] although its
selective use for high-risk patients is beneficial.[12] The expected
healthcare costs at 12 weeks for patients admitted to Canadian
ICUs for severe injuries and believed to have contraindications
for pharmacological prophylaxis for up to 2 weeks because of

8
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Figure 3. Proximal and distal deep vein thromboses: forest plot for observational studies.
a major bleeding risk were as follows: Can$55,831 for pneu-
matic compression device placement, Can$55,334 for RUSS, and
Can$57,377 for inferior vena cava filter placement. Compared
with the other 2 modalities, RUSS was associated with better
clinical outcomes and lower costs. Lifetime analysis revealed
that the expected quality-adjusted life years were similar for all
3 treatment modalities, although the costs remained the highest
for inferior vena cava filter placement. In the base case analysis,
RUSS was dominant over other modalities, as it was associated
with better clinical outcomes and lower costs (both at 12 weeks
and over a lifetime).[43]
This SRMA has several strengths. It involved a comprehen-
sive search, adhered to the recommendations for meta-analysis
of interventional studies, and used GRADE to assess the cer-
tainty in estimates.[27] We considered obtaining evidence-based
studies that utilized influential factors, such as main outcomes,
chemoprophylaxis, and other mechanical prophylactic devices.
This review also has certain limitations, and its findings
should be interpreted with caution. First, the study was based
on aggregate published data, and adjustments for patient-level
9
characteristics could not be performed. Second, significant clin-
ical heterogeneity was observed among studies owing to differ-
ences in the RUSS frequency. Four of the 5 studies included in
our review incorporated a screening test performed at least once
in the first week, followed by tests performed weekly thereaf-
ter. Furthermore, 2 of these studies recommended RUSS twice
a week.[5,32] Additionally, Fraser et al[44] suggested a week-long
interval between 2 negative screenings to exclude DVT.[44] We
found that the assessment of DVT varied across the included
studies; this heterogeneity was primarily attributed to the differ-
ing anatomical locations of DVT among these studies.
Third, the effect estimates of observational studies should be
interpreted with caution owing to possible observer bias and
residual confounders. Moreover, findings from the included
observational studies were limited by indirectness.[45] It import-
ant to mention that the GRADE methodology acknowledges the
concept of “indirectness” and offers guidance on assessing the
quality of evidence in these cases. Guyatt et al (2011)[45] elabo-
rated upon this aspect of GRADE guidelines and emphasized
the significance of downgrading the quality of evidence when
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Figure 4. Pulmonary embolism: forest plot for randomized controlled trials and observational studies.
dealing with indirect evidence. Our SRMA has closely followed
these principles. The population included in the PREVENT sub-
study was a mix of medically, surgically, and critically ill trauma
patients; in fact, patients with trauma accounted for 8% of all
the included patients.
4.2. Future research
RCTs with adjusted or adaptive methodological study designs
that incorporate Bayesian statistical methods[46] are needed to
compare the efficacies of RUSS, prophylactic inferior vena cava
filter placement, and a combination of the 2 for preventing fatal
10
PE as a clinically important VTE outcome. Further research is
also required to define the optimal RUSS frequency. Although
most included studies used the RAP score to identify asymp-
tomatic patients with trauma who were at a high risk of VTE,
further analysis is required to identify the optimal clinical VTE
risk assessment method for determining populations that will
benefit the most from RUSS. More studies are needed to confirm
the utility and efficiency of RUSS for DVT in the upper extrem-
ities and neck. The “Diagnosing Deep-vein Thrombosis Early in
Critically Ill Patients” trial is an ongoing RCT that is expected
to provide valuable information on the comparative outcomes
of RUSS and a clinician-directed approach for patients at a high
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Figure 5. Mortality: forest plot for randomized controlled trials and observational studies.
risk of DVT admitted to the ICU (Y.M. Arabi, MD, unpublished
data, ongoing, ClinicalTrials.gov Identifier: NCT05112705).
4.3. Conclusion
Our findings represent the latest and most comprehensive sum-
mary of RUSS outcomes of adults with trauma at a high risk
of DVT. In adults with trauma who are not eligible for VTE
prophylaxis and at a high risk of VTE, RUSS may result in bet-
ter DVT detection rates, a lower incidence of PE, shorter times
to DVT diagnosis, and uncertain effects on mortality. RUSS is
noninvasive and widely available with little effects on equity,
acceptability, cost-effectiveness, and feasibility. However, due
to low detection rates of clinically relevant VTE and possible
high costs, it may not be indicated for ambulatory patients with
11
trauma or for those at a low risk of VTE. Pending further data,
the very-low-certainty data in our SRMA support the use of
routine bilateral LE US for screening asymptomatic DVT in
adults with trauma who are at a high risk of VTE.
Acknowledgments
We thank Kaitryn Campbell (MSc, MLS; St. Joseph Healthcare
Hamilton, ON) for peer review of the MEDLINE search strategy.
Author contribution
Conceptualization: Abdulaziz M. Al-Sharydah, Khalid
Maghrabi, Wail Tashkandi, Marwa Amer.
Data curation: Abdulaziz M. Al-Sharydah, Khalid Maghrabi,
Wail Tashkandi, Marwa Amer.
 Al-Sharydah et al. • Medicine (2023) 102:43Medicine
Formal analysis: Abdulaziz M. Al-Sharydah, Mohammed S.
Alshahrani, Khalid Maghrabi, Wail Tashkandi, Marwa Amer.
Investigation: Abdulaziz M. Al-Sharydah, Mohammed S.
Alshahrani, Khalid Maghrabi, Wail Tashkandi, Marwa Amer.
Methodology: Abdulaziz M. Al-Sharydah, Mohammed S.
Alshahrani, Marwa Amer.
Project administration: Abdulaziz M. Al-Sharydah, Mohammed
S. Alshahrani, Khalid Maghrabi, Wail Tashkandi, Marwa
Amer.
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy
Resources: Abdulaziz M. Al-Sharydah, Mohammed S.
Alshahrani, Khalid Maghrabi, Marwa Amer
Software: Abdulaziz M. Al-Sharydah, Marwa Amer.
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 10/30/2023
Supervision: Abdulaziz M. Al-Sharydah, Mohammed S.
Alshahrani, Khalid Maghrabi, Wail Tashkandi, Marwa Amer.
Validation: Abdulaziz M. Al-Sharydah, Mohammed S.
Alshahrani, Khalid Maghrabi, Wail Tashkandi, Marwa Amer.
Visualization: Abdulaziz M. Al-Sharydah, Mohammed S.
Alshahrani, Marwa Amer.
Writing – original draft: Abdulaziz M. Al-Sharydah, Mohammed
S. Alshahrani, Khalid Maghrabi, Wail Tashkandi, Marwa
Amer.
Writing – review & editing: Abdulaziz M. Al-Sharydah,
Mohammed S. Alshahrani, Khalid Maghrabi, Wail Tashkandi,
Marwa Amer.
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