Thrombosis Research 162 (2018) 53–59

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Thrombosis Research
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Full Length Article

Effects of forced deep breathing on blood flow velocity in the femoral vein: T
Developing a new physical prophylaxis for deep vein thrombosis in patients
with plaster cast immobilization of the lower limb
⁎
Keisuke Nakanishia, Naonobu Takahiraa,b,c, , Miki Sakamotoc, Minako Yamaoka-Tojoc,
Masato Katagirid, Jun Kitagawaa
a
Sensory and Motor Control, Functional Restoration Sciences, Kitasato University Graduate School of Medical Sciences, 1-15-1, Kitasato, Minami-ku, Sagamihara-shi,
Kanagawa 252-0373, Japan
b
Department of Orthopaedic Surgery, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0373, Japan
c
Physical Therapy Course, Department of Rehabilitation, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa
252-0373, Japan
d
Department of Medical Laboratory, Kitasato University School of Allied Health Sciences, 1-15-1, Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0373, Japan

A R T I C L E I N F O A B S T R A C T

Keywords: Introduction: Patients with plaster cast immobilization of the lower limb have an estimated symptomatic venous
Blood flow velocity thromboembolism rate of 5.5%. However, there is currently no practical physical prophylaxis for deep-vein
Respiration thrombosis (DVT). The objective of this study was to examine the effects of forced deep breathing on peak blood
Deep venous thrombosis velocity in the superficial femoral vein (PBVFV), which is a surrogate measure of the efficacy of thrombopro-
Casts
phylaxis against DVT, in patients with plaster cast immobilization of the lower limb.
Primary prevention
Materials and methods: Nine young males and 18 elderly males were recruited. We immobilized the right lower
limb of each subject with a plaster splint and measured PBVFV during forced deep breathing in supine and sitting
positions.
Results: In all subjects, PBVFV during forced deep breathing in both positions was significantly higher than at
rest. There was no significant difference in the PBVFV change ratio for three breathing rates in the sitting
position for the young subjects (15 breaths/min: 415%, 5 breaths/min: 475%, 3 breaths/min: 483%), whereas
that for the elderly subjects at 3 breaths/min (449%) was significantly higher than that at 15 breaths/min
(284%).
Conclusions: Forced deep breathing significantly increased PBVFV in patients with plaster cast immobilization of
the lower limb in both supine and sitting positions. Testing the efficacy and adherence in clinical contexts, and
following up with the incidence rate of DVT in future studies, is necessary for the development of a new physical
prophylaxis for DVT.

1. Introduction
The incidence rate of a first venous thromboembolism (VTE), i.e.,
deep vein thrombosis (DVT) and pulmonary embolism (PE), is 1–2 per
1000 person-years in the general population, and increases with age (up
to 1% per year) in the elderly [1–5]. The mortality rate of VTE is high,
and is estimated at 1.8% in the first month in non-cancer patients with a
DVT and 6.8% in non-cancer patients with a pulmonary
thromboembolism (PTE) [1]. The high risk of VTE in patients under-
going orthopedic surgery is well documented; plaster cast immobiliza-
tion in particular is linked with an increased risk of symptomatic VTE,
and lower limb immobilization specifically is associated with a 73-fold
increased risk of VTE [6]. The most recent meta-analyses and reviews in
patients with plaster cast immobilization of the lower limb, involving
1456 patients [7] and 1490 patients [8], show that VTE incidence ap-
proaches 20% without prophylaxis. Evidence from randomized

Abbreviations: ACCP, American College of Chest Physicians; BMI, body mass index; DVT, deep vein thrombosis; ICC, intraclass correlation coefficients; IPC, intermittent pneumatic
compression; PBV, peak blood velocity; PBVFV, peak blood velocity in the superficial femoral vein; VTE, venous thromboembolism
⁎
Corresponding author at: Department of Rehabilitation, Kitasato University School of Allied Health Sciences, 1-15-1, Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374,
Japan.
E-mail addresses: takahira@med.kitasato-u.ac.jp (N. Takahira), mikis@kitasato-u.ac.jp (M. Sakamoto), myamaoka@med.kitasato-u.ac.jp (M. Yamaoka-Tojo),
mkata@kitasato-u.ac.jp (M. Katagiri), kitagawa@kitasato-u.ac.jp (J. Kitagawa).

https://doi.org/10.1016/j.thromres.2017.12.013
Received 26 August 2017; Received in revised form 20 December 2017; Accepted 21 December 2017
Available online 23 December 2017
0049-3848/ © 2017 Elsevier Ltd. All rights reserved.
K. Nakanishi et al.
controlled trials shows that the use of low-molecular-weight heparin
leads to a decrease in the mean VTE incidence rate (17.1% to 9.6%)
during plaster cast immobilization [7]. However, compared to the ex-
tensive trials on major joint replacement or hip fracture surgery, there
is a paucity of studies on the use of thromboprophylaxis in patients with
lower limb plaster cast immobilization, and the risk of VTE in these
patients is not sufficient to justify the use of anticoagulant prophylaxis,
since the risk of bleeding is considerable (0.3% major bleeding) [8,9].
Therefore, the 9th American College of Chest Physicians (ACCP)
guidelines suggest that the benefit of pharmacological thrombopro-
phylaxis in patients with isolated lower leg injuries requiring leg im-
mobilization is unclear. Also, the patient population was quite hetero-
geneous, patients with a higher risk for VTE were excluded, and
detailed information with regard to immobility was not provided [9].
Further, the latest randomized controlled trial (POT-CAST trial) shows
that prophylaxis with low-molecular-weight heparin for immobilization
due to casting was not effective for the prevention of symptomatic
venous thromboembolism [10]. Developing a highly cost-effective
prophylaxis for VTE to replace pharmacological prophylaxis is therefore
an urgent priority for patients with plaster cast immobilization of the
lower limb.
Physical DVT prophylaxis eliminates serious complications such as
bleeding, and is currently receiving considerable attention. For in-
stance, the 9th ACCP guidelines recommend the use of intermittent
pneumatic compression (IPC) to prevent DVT in patients undergoing
total hip arthroplasty, total knee arthroplasty, or hip fracture surgery
[9]. The application of IPC therapy to patients undergoing lower limb
plaster cast immobilization for ruptured Achilles tendons reduced the
incidence of DVT at two weeks post-operatively, but not at six weeks
post-operatively [11]. In addition, it has been hypothesized that ad-
juvant IPC beneath an orthotic would reduce the risk of DVT during
lower limb post-operative immobilization, but such treatment cannot
be recommended due to the high DVT incidence rate associated with
malfunctioning IPC devices [12]. Indeed, the application of an IPC
device to a lower limb beneath a plaster cast in patients with ruptured
Achilles tendons or ankle fractures was associated with high rates
(50%) of adverse events (e.g., skin ulceration or maceration), in addi-
tion to inconclusive evidence for VTE prevention [13]. Therefore, the
benefits of IPC therapy beneath a plaster cast are unclear. In a previous
study, we applied an IPC device to the thigh of subjects with below-
knee plaster cast immobilization, and achieved a significant increase in
peak blood velocity (PBV) in the superficial femoral vein and the po-
pliteal vein [14]. However, this method is not applicable for patients
with above-knee plaster casts. In summary, there is currently no prac-
tical physical prophylaxis for DVT in patients with plaster cast im-
mobilization of the lower limb.
We thus considered taking advantage of the respiratory muscle
pump, which, along with the skeletal muscle pump, is widely ac-
knowledged as a powerful mechanism for accelerating venous return
from the lower limb. For example, it has been suggested that marked
increases in PBV in the femoral vein occur throughout a predominantly
ribcage inspiration [15,16], and non-forced deep breathing in a supine
position results in a 1.5-fold increase in PBV in healthy young males
[20]. Lower limb PBV is considered a surrogate measure of prophylactic
effects against thrombosis, because the use of IPC devices that espe-
cially affect PBV is associated with a significantly lower rate of VTE
[18,19]. Although deep breathing may be a useful prophylactic for
DVT, its preventive effects are probably minimal, because the increase
in PBV achieved is lower than that generated by IPC or ankle exercise
[14,20,21]. On the other hand, increased respiratory muscle excursion
can augment the pressure changes in the intrahepatic inferior vena cava
[22], and therefore enhance respiratory modulation of the femoral
venous return [23]. In addition, the respiratory collapse of the inferior
vena cava during slow respiration with inspiratory pause was greater
than that in normal respiration [24]. From the above, we understand
that venous return is affected by respiratory patterns (respiratory
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Thrombosis Research 162 (2018) 53–59
muscle pressure, respiratory rate, and breath holding), and that forced
deep breathing effectively augments PBV in the lower limb.
The objective of this study was to examine the effects of forced deep
breathing on PBV in the superficial femoral vein (PBVFV), which is a
surrogate measure of thromboprophylaxis efficacy, and to consider
forced deep breathing as a physical prophylaxis for DVT in patients
with plaster cast immobilization of the lower limb.
2. Materials and methods
2.1. Study participants and characteristics
This study was approved by the Ethics Committee of the Kitasato
University School of Medicine (no. 2013–004). We recruited nine young
healthy male volunteers and 18 elderly male volunteers, none of whom
had a medical history, but who were registered with silver human re-
source centers. Based on the World Health Organization and the
Ministry of Health, Labour and Welfare, we defined people aged 65 or
above as “elderly”, and aged 15 to 24 as “young”. We recorded age,
height, body weight, body mass index (BMI), Brinkman index (a mea-
sure of cigarette use) [25], and medications for all subjects, and all
eligible subjects provided written informed consent before inclusion in
the trial. Exclusion criteria included any of the following conditions:
thrombophlebitis, arteriosclerosis obliterans, any thromboembolic
event, malignant tumors, lower limb or pelvic bone fractures, sensory
disturbances, inflammatory diseases, swelling, necrosis, epidermiza-
tion, cerebrovascular disorders, heart failure, respiratory illness, kidney
failure, systolic blood pressure above 180 mm Hg, and a history of
diastolic blood pressure above 110 mm Hg.
2.2. Study procedure and measurements with Doppler ultrasound
Subjects were advised to avoid strenuous exercise, such as jogging,
and to consume liquids as usual on the day of the test. Each subject
changed into shorts in the examination room, and we then immobilized
his right lower leg and ankle with a plaster splint. The subjects were
instructed to relax and to avoid talking loudly, falling asleep, and
contracting body muscles as much as possible during the protocol.
PBVFV was measured in the supine and sitting positions, using pulsed
Doppler ultrasound with a 7.5-MHz linear probe interfaced with an
ultrasound unit (Pro Sound SSD-4000, ALOKA, Inc., Wallingford,
United States of America). The PBVFV was measured from the anterior
side, approximately 3 cm distal to the deep femoral vein junction. The
Doppler angle of the superficial femoral vein was maintained at < 60°.
First, PBVFV was measured in triplicate with the subjects at rest in the
supine position. Next, we measured PBVFV in duplicate during forced
deep breathing, starting with the fastest breathing rate and progres-
sively slowing down (15, then 5, then 3 breaths/min) (Fig. 1A). The
mean values obtained from these measurements were used in the
analysis. The subjects then sat on a chair, with thighs parallel to the
floor and knees bent at 60 degrees, and the same protocol was used to
measure PBVFV. We ensured that the subjects sat far enough forward to
avoid compressing the superficial femoral vein. All measurements were
taken by the same skilled tester. Prior to the primary experiment, we
confirmed the intraclass correlation coefficients (ICC) of the blood flow
measurements in a preliminary experiment, and obtained confirmed
excellent measurement accuracy [ICC (1, 1) = 0.86; ICC (1, 3) = 0.95].
We removed the plaster splint immediately after completing the mea-
surements; this process took approximately 1.5 h. The subjects also
practiced forced deep breathing before the measurements were taken,
and we confirmed that they experienced no dizziness or respiratory
discomfort as a result of the deep breathing. A physical therapist was
present to monitor the condition of the subjects and manage risks
during the experiment.
K. Nakanishi et al. Thrombosis Research 162 (2018) 53–59

Fig. 1. Protocol of blood flow measurement (A) and forced deep

breath (B).
PBVFV = peak blood velocity in the superficial femoral vein.
B/min: breaths per minute.

2.3. Forced deep breathing

The subjects were instructed to take forced deep breaths at rates of

15 breaths/min, 5 breaths/min, and 3 breaths/min consecutively.
Respiratory patterns (i.e., thoracic or abdominal) was not prescribed,
and each subject carried out forced deep breathing according to their
preference. Subjects inspired air as fast as possible during the inspira-
tion phase, and held maximum inspiration until the commencement of
the expiration phase. Similarly, during the expiration phase, the sub-
jects expired air as fast as possible, and held maximum expiration until
commencement of the next inspiration phase. Inspiration and expira-
tion alternated every 2 s at 15 breaths/min, 6 s at 5 breaths/min, and
10 s at 3 breaths/min respectively for three breath cycles (Fig. 1B). A
metronome was used to monitor breathing rate, and the degree of
dyspnea experienced during forced deep breathing was assessed using
the modified Borg scale [26] (Fig. 2). A spirometer (Auto Spiro AS-507,
Minato Medical Science, Ltd., Osaka, Japan) was used to assess each
subject's respiratory function, vital capacity, forced vital capacity, 1-s
flow rate and volume, and inspiratory and expiratory muscle strength.
Fig. 2. Modified Borg Scale.
2.4. Statistical analysis

Descriptive data for the subjects are reported as means with stan-
dard deviations. The PBVFV change ratio (%) was calculated using the
following formula: PBVFV during forced deep breathing (cm/s) × 100/
PBVFV during rest (cm/s). A Mann-Whitney U test was used to examine
differences in subject characteristics and respiratory function between
young and elderly subjects; a Wilcoxon signed-rank test was used to
examine differences in PBVFV between rest and forced deep breathing;
and a Kruskal Wallis test and Steel test were used to examine differ-
ences in the PBVFV change ratio and modified Borg Scale among the
three breathing rates. We used JMP 13 (Statistical Analysis System
Institute, Japan) for all statistical analyses except power analysis, and
the level of significance was set at P ≤ 0.05. The sample size was es-
timated using a software for power and sample size calculation (version
3.0, Department of Biostatistics, Vanderbilt University, United States of

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K. Nakanishi et al. Thrombosis Research 162 (2018) 53–59

Table 1
Subject's characteristics & respiration function.

Characteristic Young (n = 9) Old (n = 18) P-value

Age (yrs) 22.8 ± 3.6 70.0 ± 4.6 –

Body mass index (kg/m2) 23.7 ± 2.9 22.5 ± 2.9 0.37
Brinkman index 0 440 ± 729 –
Vital capacity Measured value (L) 4.72 ± 0.37 3.36 ± 0.54 < 0.01
Predicted value (%) 94.9 ± 7.2 93.1 ± 14.4 0.37
Forced vital capacity Measured value (L) 4.72 ± 0.44 3.13 ± 0.42 < 0.01
Predicted value (%) 96.3 ± 8.6 89.2 ± 12.4 0.22
1 s flow volume Measured value (L) 4.02 ± 0.51 2.34 ± 0.36 < 0.01
Predicted value (%) 91.8 ± 10.0 82.7 ± 13.7 < 0.05
1 s flow rate Measured value (L) 85.0 ± 6.7 75.1 ± 7.4 < 0.01
Predicted value (%) 94.8 ± 7.7 93.1 ± 9.2 0.35
Strength of inspiratory muscle Measured value (L) 137.0 ± 33.6 108.6 ± 27.6 0.13
Predicted value (%) 101.6 ± 25.2 102.3 ± 29.3 0.92
Strength of expiratory muscle Measured value (L) 109.2 ± 25.3 63.9 ± 20.4 < 0.01
Predicted value (%) 93.2 ± 20.7 86.0 ± 29.6 0.92
(Mean ± SD)

Mann-Whitney U test.

America). Prior to measurements, statistical parameters based on pre-
vious studies (statistical power, 0.8; significance level, 0.05; difference
of average, 6; standard deviation, 8) were imputed into the software
[17]. The results indicated that an estimated 16 cases were required for
our study.
3. Results
3.1. Subject characteristics
There was no significant difference in BMI between the young and
elderly subjects, and there were no smokers among the young subjects.
In elderly subjects, the Brinkman index (i.e., the number of cigarettes
smoked per day multiplied by the number of years the subject had
smoked) averaged 440 in elderly subjects, which indicated moderate
smoking [25]. In spirometry measurements, all measured values except
the strength of inspiratory for the elderly subjects were significantly
lower than those for the young subjects (P < 0.01). In predicted va-
lues, only the 1 s flow volume for the elderly subjects was significantly
lower than that for the young subjects (P < 0.05, Table 1).
3.2. PBVFV
PBVFV under forced deep breathing was significantly higher than at
rest in both positions in the young and elderly subjects (P < 0.01,
Table 2).
3.3. PBVFV change ratio
There were no significant differences in the PBVFV change ratio of
the young subjects between the three breathing rates in either the su-
pine (15 breaths/min: 173 ± 23%, 5 breaths/min: 180 ± 57%,
3 breaths/min: 195 ± 63%, P < 0.01, Fig. 3A) or the sitting position
(15 breaths/min: 415 ± 186%, 5 breaths/min: 475 ± 177%,
3 breaths/min: 483 ± 284%, P < 0.01, Fig. 3B). However, for the
elderly subjects, in the supine position the PBVFV change ratio at
5 breaths/min was significantly higher than that at 15 breaths/min and
lower than that at 3 breaths/min (15 breaths/min: 186 ± 40%,
5 breaths/min: 219 ± 45%, 3 breaths/min: 249 ± 81%, P < 0.05,
Fig. 4A). In the sitting position, it was significantly higher at 3 breaths/
min than at 15 breaths/min (15 breaths/min: 284 ± 115%, 5 breaths/
min: 383 ± 195%, 3 breaths/min: 449 ± 210%, P < 0.05, Fig. 4B).
3.4. Dyspnea during forced deep breathing
There were no significant differences in the modified Borg scale
among the three breathing rates for the young subjects, whereas in the
elderly subjects, the modified Borg scale at 15 and 5 breaths/min was
lower than that at 3 breaths/min (P < 0.05, Table 3).
4. Discussion
In this study, forced deep breathing increased PBVFV irrespective of
posture and age. In the young subjects, it resulted in at most a 2.0- and

Table 2
PBVFV at rest and forced deep breath (cm/s).

Posture Breath pace Rest Forced deep breath P-value

Young group (n = 9) Supine 15 breaths/min 24.3 ± 5.6 41.8 ± 10.9 < 0.01
5 breaths/min 24.6 ± 5.7 42.1 ± 8.5 < 0.01
3 breaths/min 24.2 ± 5.9 45.0 ± 9.8 < 0.01
Sitting 15 breaths/min 7.6 ± 1.7 30.8 ± 12.8 < 0.01
5 breaths/min 6.7 ± 1.9 31.3 ± 11.6 < 0.01
3 breaths/min 8.4 ± 3.9 36.2 ± 15.9 < 0.01
Old group (n = 18) Supine 15 breaths/min 11.1 ± 3.2 20.2 ± 5.2 < 0.01
5 breaths/min 11.0 ± 3.5 23.6 ± 7.5 < 0.01
3 breaths/min 10.5 ± 3.4 24.8 ± 7.2 < 0.01
Sitting 15 breaths/min 6.4 ± 1.6 18.0 ± 7.7 < 0.01
5 breaths/min 6.1 ± 1.1 23.9 ± 13.6 < 0.01
3 breaths/min 5.9 ± 1.2 26.3 ± 13.0 < 0.01
(Mean ± SD)

Wilcoxon signed-rank test.

PBVFV = peak blood velocity in the superficial femoral vein.

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K. Nakanishi et al. Thrombosis Research 162 (2018) 53–59

Fig. 3. Change ratio of PBVFV at forced deep breath in young

800 n.s. n.s.
800 group (n = 9).
Change ratio of PBVFV (%)

PBVFV = peak blood velocity of superficial femoral vein.

700 700 B/min: breaths per minute.
n.s.: not significant.
600 600
500 500
400 400
300 300
200 200
100 100
0 0
15 B/min 5 B/min 3 B/min 15 B/min 5 B/min 3 B/min
(A) Supine (B) Sitting

4.8-fold increase in PBVFV in the supine and sitting positions respec- Table 3
tively; in the elderly subjects, it resulted in at most a 2.4- and 4.5-fold Modified Borg Scale at rest and forced deep breath.
increase, respectively. Previous research investigating the relationship
Posture 15 breaths/min 5 breaths/min 3 breaths/min
of deep breathing with PBVFV in the lower limb was limited to non-
forced breathing conditions and the supine position in youths or adults. Young group Supine 3.3 ± 1.7 3.1 ± 1.5 3.9 ± 2.2
Therefore, this is the first study that has measured PBVFV during forced (n = 9) Sitting 3.3 ± 1.4 2.6 ± 1.2 3.7 ± 1.9
Old group (n = 18) Supine 3.1 ± 1.4⁎⁎ 3.3 ± 1.2⁎⁎ 4.7 ± 1.6
deep breathing in elderly subjects, and compared with the young sub-
Sitting 2.5 ± 1.0⁎⁎ 2.7 ± 1.3⁎ 4.0 ± 1.7
jects while changing the postures. Non-forced deep breathing in the (Mean ± SD)
supine position has been reported to result in a 1.5-fold increase in
PBVFV in healthy young males [17], but the present study showed that Kruskal Wallis test and Steel test.
⁎
forced deep breathing, irrespective of respiratory rate, could increase P < 0.05, vs 3 breaths/min.
⁎⁎
P < 0.01, vs 3 breaths/min.
PBVFV more efficiently. A possible explanation for this result is that
maximal airflow during inspiration is determined by subject effort and
the force-velocity relationship of the inspiratory muscles [27]. There- Although the different breathing rates did not significantly affect
fore, we speculate that the respiratory pump function was augmented the PBVFV change ratio in the young subjects, a breathing rate of
because the subjects took forced deep breaths for maximal tidal volume 3 breaths/min was most effective at increasing PBVFV in the elderly
and flow speed. In addition, the present study demonstrated significant subjects. The diameter of the vena cava is significantly compressed
increases in PBVFV caused by forced deep breathing in a sitting posi- when holding maximum inspiration for 3 s, so sufficient inspiration is
tion, which have not been previously reported. In the sitting position, a an important factor for determining the efficacy of the respiratory
large amount of venous blood pools in the lower limbs, and the muscle pump [24]. In the present study, the maximum inspiration phase
pump of the lower limbs is the predominant mechanism responsible for lasted < 2 s at a breathing rate of 15 breaths/min. Further, more than
venous return [28–31]. Nevertheless, the respiratory pump can also half of the elderly subjects had restrictive, obstructive, or other venti-
assist the venous return of blood in the lower limb, albeit via a different latory defects, and had a low forced vital capacity. As a result, they
mechanism than the muscle pump. Therefore, we assume that forced could not utilize the respiratory pump effectively at a breathing rate of
deep breathing can also effectively increase PBVFV while sitting. 15 breaths/min, and we suggest that such patients should take forced
deep breaths at a rate below 15 breaths/min. However, the modified

Fig. 4. Change ratio of PBVFV at forced deep breath in old

* group (n = 18).
800 800 PBVFV = peak blood velocity of superficial femoral vein.
Change ratio of PBVFV (%)

B/min: breaths per minute.

700 700 *: P < 0.05.
*
600 600
500 * 500
400 400
300 300
200 200
100 100
0 0
15 B/min 5 B/min 3 B/min 15 B/min 5 B/min 3 B/min
(A) Supine (B) Sitting

57
K. Nakanishi et al.
Borg scale indicated that dyspnea in the elderly subjects was higher at a
breathing rate of 3 breaths/min than at 5 and 15 breaths/min. Since
adherence is important for DVT prevention [9], it is impractical for
elderly patients take forced deep breath at 3 breaths/min. Based on the
above, we suggest that both young and elderly patients should take
forced deep breaths at a comfortable rate, and that elderly patients with
ventilatory defects should take forced deep breaths at about 5 breaths/
min, with sufficient inspiration.
Previous studies reported that ankle exercise in the supine position,
with and without deep breathing, resulted in a 2.1-fold and 2.6-fold
increase in PBVFV, respectively [17]. Additionally, DVT incidence was
significantly lower in orthopedic surgery patients who performed ankle
exercise than in the control group (total DVT incidence of 1.0% vs.
8.2%) [32]. The application of a portable IPC device to the foot and calf
in the supine position resulted in a 1.4-fold increase in PBVFV [33], and
we previously reported a 1.9 to 2.3-fold and a 2.4 to 2.6-fold increase in
PBVFV, in the supine and sitting positions, respectively, using a similar
IPC device applied to the thigh [14]. According to a multicenter ran-
domized controlled study of DVT prophylaxis, the use of portable IPC
devices for thromboprophylaxis is comparable with the use of some
anticoagulants [34], and is recommended by the ACCP Guidelines for
DVT prevention [9]. However, the present study demonstrates that
forced deep breathing promotes PBVFV to an equivalent or greater
extent than IPC devices or ankle exercise. Lower limb PBV is considered
a surrogate measure of the efficacy of prophylaxes against thrombosis
[18,19]. From the above, high PBV-enhancing effects of forced deep
breathing is an important insight to DVT prevention in patients with
plaster cast immobilization of the lower limb.
Furthermore, forced deep breathing may be relevant in extra-clin-
ical settings; DVT incidents are not limited to plaster-cast-immobilized
patients, and can occur in disaster-stricken areas. One month after the
great East Japan earthquake, DVT incidence reached a maximum of
45.6% in evacuees at shelters or temporary emergency housings, three
times higher than in the same period of the previous year. In addition, a
high DVT incidence (over 18.6%) persisted for at least four months
following the earthquake [35]. The cramped and crowded conditions in
the tsunami-flooded shelters could have contributed to this phenom-
enon by restricting evacuees' physical activity and facilitating the
stagnation of blood in their lower extremities [36]. Forced deep
breathing can increase PBVFV without the need for any special devices
and be conducted in cramped spaces. Thus, we aim to introduce forced
deep breathing as a prophylaxis against DVT, especially for patients
suffering from trauma, disuse of their lower legs, or paralysis of the
peroneal or sciatic nerves in future studies.
The strain associated with holding the breath may elicit sharp
fluctuations in autonomic nervous activity and could affect blood
pressure or heart rate [37]. Therefore, we advise that forced deep
breathing be performed under professional medical supervision, with
special attention paid to symptoms of syncope or dizziness, particularly
for the elderly and for patients with cardiovascular disease. In addition,
forced deep breathing is not advised for patients who already have
DVT, due to the risk of thrombus dislodgement. In such cases, the
doctor's advice should be followed strictly, and we have to determine
whether DVT is present by imaging before practice forced deep
breathing.
This study is the first to examine the PBVFV-promoting effect of
forced deep breathing. A particularly noteworthy finding is that deep
breathing increased PBVFV regardless of breathing rate, posture, and
age. Forced deep breathing may be conducted in clinical settings,
especially for patients who are ineligible for pharmacotherapy for
various reasons, such as patients with high bleeding risk, or whose in-
surance coverage for anticoagulants has expired. Forced deep breathing
has the advantage of increasing PBVFV without the need for any special
devices, but it is not without some limitations. First, although forced
deep breathing increased PBV immediately, it remains unclear if this
effect can be sustained. Strong adherence is essential for DVT
58
Thrombosis Research 162 (2018) 53–59
prevention; for example, it is recommended that IPC devices be applied
for over 18 h per day [9]. It is currently impractical for patients to
maintain the forced breathing pattern, and there have been no reports
on the persistence of PBV-enhancing effects or effective deep breathing
patterns. Therefore, we need to examine effective respiration, including
breathing rates and patterns, in future studies. Furthermore, this study
was conducted in healthy individuals, and it is possible that forced deep
breath has different effects in patients with severe respiratory or cir-
culatory dysfunction. The feasibility and outcomes of the exercises
should also be verified in older individuals. Therefore, future studies
should focus on improving patient adherence and determining the
persistence of PBV-enhancing effects of forced deep breathing, espe-
cially in patients with respiratory or circulatory dysfunction.
5. Conclusion
Forced deep breathing significantly increased PBVFV in both supine
and sitting positions. Testing the efficacy and the adherence in clinical
contexts, and following up with the incidence rate of DVT in future
studies, is necessary for the development of a new physical prophylaxis
for DVT in patients with plaster cast immobilization of the lower limb.
Authorship contributions
Keisuke Nakanishi was the lead investigator in this study, conducted
the study, wrote the first draft of the manuscript, and approved the final
version of the manuscript. Naonobu Takahira (Orthopedic Surgeon,
Professor, M.D., Ph.D) conceived, designed, and conducted the study,
assisted with data analysis, proofread the manuscript, and approved the
final version of the manuscript. Miki Sakamoto (Registered Physical
Therapist, Assistant Professor, Ph.D) designed and conducted the study,
and assisted with data analysis. Minako Yamaoka-Tojo (Cardiologist,
Associate Professor, M.D., Ph.D), Masato Katagiri (Respiratory
Physician, Professor, M.D., Ph.D.), Jun Kitagawa (Professor, PhD) as-
sisted with the design and conducting of the study, as well as data
analysis.
Conflict of interest
The authors declare no conflict of interest with Medical
Compression Systems, Inc.
Acknowledgements
We sincerely thank Junior Associate Professor Keika Hoshi (D.D.S.,
M.D.S., Ph.D., Kitasato Clinical Research Center) and Yasutoshi
Sakamoto (Research Staff, Kitasato Clinical Research Center) for their
advice on experimental design and their assistance in the interpretation
of the results of this study. We also greatly appreciate the contributions
of our study subjects to this study.
Funding sources
This study was funded by the Japan Society for the Promotion of
Science (JSPS) KAKENHI Grant Number 26462250. Naonobu Takahira
had full access to all data in this study, and takes responsibility for the
integrity of the data and the accuracy of data analysis. All analyses were
conducted by Keisuke Nakanishi.
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