801440

research-article2018
CRE0010.1177/0269215518801440Clinical RehabilitationBarbalho et al.

CLINICAL
Original Article REHABILITATION

Clinical Rehabilitation

Addition of blood flow restriction 1­–8

© The Author(s) 2018
Article reuse guidelines:
to passive mobilization reduces sagepub.com/journals-permissions
DOI: 10.1177/0269215518801440
https://doi.org/10.1177/0269215518801440

the rate of muscle wasting in journals.sagepub.com/home/cre

elderly patients in the intensive

care unit: a within-patient
randomized trial

Matheus Barbalho1,2 , Angel Caroline Rocha3,

Thamires Lorenzet Seus3, Rodolfo Raiol4, Fabrício
Boscolo Del Vecchio5 and Victor Silveira Coswig6 

Abstract
Objective: To evaluate the addition of blood flow restriction to passive mobilization in patients in the
intensive care unit.
Design: The study was a within-patient randomized trial.
Setting: Two intensive care units in Belém, from September to October 2017.
Subjects: In total, 34 coma patients admitted to the intensive care unit sector, and 20 patients fulfilled
the study requirements.
Interventions: All participants received the passive mobilization protocol for lower limbs, and blood
flow restriction was added only for one side in a concurrent fashion. Intervention lasted the entire
patient’s hospitalization time.
Main outcome measurement: Thigh muscle thickness and circumference.
Results: In total, 34 subjects were enrolled in the study: 11 were excluded for exclusion criteria, 3 for
death, and 20 completed the intervention (17 men and 3 women; mean age: 66 ± 4.3 years). Despite both
groups presented atrophy, the atrophy rate was lower in blood flow restriction limb in relation to the

1Faculdade de Educação Física e Dança, Universidade Federal 6Faculdade

de Educação Física, Universidade Federal do Pará,
de Goiás, Goiânia, Brasil Castanhal, Brasil
2Centro de Ciências Biológicas e da Saúde, Universidade da
Corresponding author:
Amazônia, Belém, Brasil
3Centro de Ciências da Saúde, Universidade Católica de Matheus Barbalho, Centro de Ciências Biológicas e da Saúde,
Universidade da Amazônia, Av. Alcindo Cacela, 287, Belém -
Pelotas, Pelotas, Brasil
4Centro de Ciências Biológicas e da Saúde, Centro PA 66065-219, Brasil.
Email: matheussmbarbalho@gmail.com
Universitário do Estado do Pará, Belém, Brasil
5Escola Superior de Educação Física, Universidade Federal de

Pelotas, Pelotas, Brasil

2 Clinical Rehabilitation 00(0)

control limb (–2.1 vs. –2.8 mm, respectively, in muscle thickness; P = 0.001). In addition, the blood flow
restriction limb also had a smaller reduction in the thigh circumference than the control limb (–2.5 vs.
–3.6 cm, respectively; P = 0.001).
Conclusion: The use of blood flow restriction did not present adverse effects and seems to be a valid
strategy to reduce the magnitude of the rate of muscle wasting that occurs in intensive care unit patients.

Keywords
Muscle atrophy, passive manipulation, intensive care unit, blood flow restriction

Received: 24 January 2018; accepted: 27 August 2018

Introduction Recently, a systematic review with meta-analysis

All patients residing in an intensive care unit are at
risk of acquiring quickly and significant muscle
wasting, which is likely to impede their recovery.1
In this sense, muscle weakness and atrophy are two
of the recurrent complications, since muscle
strength losses from 4% to 5% are expected each
week from bed rest time2 and 10% to 15% from
complete rest.3 Mainly, it occurs due to metabolic
activity and circulatory issues3 to reduce neural
input2 related to the fact that lower limb muscles
become antigravitational in supine position.
After two months of inactivity, a muscle may
lose half of its volume4 and it is related to adverse
effects as muscle weakness and critical illness neu-
romyopathy. The combination of decreased muscle
strength, limited muscle endurance, and muscular
wasting leads to incoordination of extremities’
movements and may limit the ability of patients in
their daily life activities.5 On the other hand, despite
passive mobilization protocols6,7 and neuromuscular
electrical stimulation,1 there is no consensus about
effects on wasting rate reduction.
The purpose of passive mobilization is based on
the maintenance of mass and muscle strength, and it
is frequently used in intensive care unit.8 In addition,
recent evidence suggests that blood flow restriction
may be an effective method for reducing the rate of
muscle wasting.9 This is due to the fact that blood
flow restriction can promote a monitored and con-
trolled tissue hypoxia, with consequent metabolite
accumulation, which increases local stress and con-
tributes to significant gains in muscle mass, even
with very low external loads or even in walking.10
pointed out that exercises with blood flow restriction
are positive in the treatment of people at risk of sar-
copenia, especially the elderly.11
The blood flow restriction method consists of
focal and partial occlusion of veins and arteries at
the level of an arteriovenous junction, promoting a
decrease in blood flow.12 This intervention promotes
muscle mass and muscle strength gains in athletes,
physically active, and sick people.13 In addition, the
use of blood flow restriction seems safe since it does
not increase the risk of thrombosis, as well as pre-
sents a low risk of nerve damage in individuals who
perform vascular occlusion without force exertion,14
and there are clear indications that the vascular
restraint technique is beneficial for patients who
have undergone immobilization.15 Therefore, in
addition to the fact that blood flow restriction is an
innovative therapy in the intensive care unit, when
associated with motor physical therapy, it could
minimize the muscular wasting resulting from long-
term hospitalization. In this way, the purpose of the
present study was to evaluate the effects of blood
flow restriction on muscle wasting of hospitalized
elderly individuals in intensive care unit, submitted
to conventional motor physical therapy with passive
mobilization protocol.
Methods
The study was a within-patient randomized trial in
which lower limbs were independently allocated
to one of the proposed interventions. This design
was chosen to avoid interindividual responses, and
Barbalho et al. 3
Figure 1.  Flow diagram.
interventions were given concurrently. The regis-
tration number is RBR-5kqsnp in the Brazilian
Registry of Clinical Trials. The Research Ethics
Committee of the Catholic University of Pelotas
(UCPel) under number 68338417.7.0000.5339
approved the study, and all participants or their
legal guardians were informed of possible risks,
benefits, and discomforts that test and training
protocols could cause. The inclusion criterion was
to be admitted to the intensive care unit sector of
two reference hospitals in Belém, from September
to October 2017, and to be admitted to the passive
mobilization protocol, with the following param-
eters: partial pressure of oxygen/fraction of
inspired oxygen (PaO2 / FiO2) > 300, oxygen
saturation <140 bpm, systolic blood pressure 90–
180 mmHg, arterial blood pressure <60 bpm, arte-
rial blood pressure (PaO2) >90%, diastolic
50–120 mmHg, respiratory rate of up to 30 breaths
per minute, and absence of uncontrolled eletrocar-
diogram arrhythmias.
After eligibility screening of the patients by the
inclusion criteria, a simple random sampling was per-
formed to define the lower limbs that should receive
experimental blood flow restricted (BFR) or control
(CTL) treatments (Figure 1). To enable a blinded
analysis, randomization and data coding were accom-
plished by the first author, while data analysis was
performed by the last author. In addition, due to the
coma situation, it is possible to consider that subjects
4 Clinical Rehabilitation 00(0)
Table 1.  Baseline descriptive data (n = 20).
Age (years) 66 ± 4.3
Body mass (kg) 79.6 ± 7
Height (cm) 172 ± 5
Systolic blood pressure (mmHg) 113.5 ± 12.6
Diastolic blood pressure (mmHg) 66 ± 8.2
Basal heart rate (bpm) 73.7 ± 6.5
Oxygen saturation (%) 96.5 ± 1.5
were blinded as well. Those who did not complete
evaluations or interventions, sessions were excluded.
After that, pre-intervention measures of thigh muscle
thickness and circumference were taken and the pas-
sive mobilization protocol started, which was per-
formed once a day, throughout the patient’s
hospitalization time. To perform blood flow restric-
tion, the cuff (WCS, Scientific Clinic Leg) was placed
in the thigh’s proximal region, and pressure is applied
to restrict the blood flow. Pressure values were estab-
lished at 80% of the patient’s anterior tibial artery sys-
tolic blood pressure. The intervention was held every
day of the patient’s hospitalization. All participants
had a controlled diet verified by the nutritional sector
of the hospital.
After the cuff placed for the occluded limb, the
passive mobilization protocol was performed with
three sets of 15 knee flexion-extension movements,
considering 2 seconds in the flexion phase and
2 seconds in the extension phase. The sessions
were performed by professionals who work in the
intensive care unit, duly masked and with specific
uniforms, while the protocol of passive mobiliza-
tion was performed alternately among the mem-
bers during the resting phase of the opposite limb.
After an interruption of sedation and the patient
with independent motor control, post-intervention
measures were performed.
The procedures for pre-blood flow restricted and
post-evaluation were through quadriceps muscular
thickness, analysis using the ultrasound method
(Toshiba Tossbe Model, linear transduction
7.5 MHz). The procedure was performed by placing
the transducer in the medial thigh and proximal thigh
to obtain the images and measurements; a single
analysis was performed on each participant, per-
formed by the same evaluator.16 The circumference
of the medial portion of the thigh was measured,
considering the length between the superior anterior
iliac spine and the patella superior border. Finally, the
muscle strength scale was used to assess the overall
muscular strength, after the patient left the sedation
state, and was able to obey commands and perform
strength tests.17 However, in the present study, only
lower limb scores were used for post-sedation
verification.
Analysis
After Shapiro–Wilk’s tests for normality, data are pre-
sented as mean and standard deviation. Absolute val-
ues were compared by two-way analysis of variance
(ANOVA) for repeated measures (Trained/Untrained
Leg × Moment) with Bonferroni’s post hoc. When
interactions were identified, deltas and absolute dif-
ferences between pre and post were calculated and
compared by paired t test. Effect sizes were calculated
by Cohen’s d. For correlations, the Pearson coeffi-
cient was calculated. The SPSS version 22.0 was used
for analysis, and significance was set at 5%.
Results
In the data collection period, 34 individuals were
admitted to the intensive care unit sector of the
hospital; 14 were excluded by exclusion criteria
(n = 11) and death (n = 3). For this investigation, 17
men and 3 women completed the intervention, and
baseline descriptive data are presented in Table 1.
Enrolled subjects ingested 1560 ± 156.5 kcal/day
(60.5 ± 10 kcal were from proteins), and interven-
tion lasted 11 ± 2.2 days. When the patient was
able to obey commands, the global and lower limbs
muscle strength scale scores were 50.9 ± 2.78 and
24.8 ± 3, respectively.
Considering absolute comparisons, within-sub-
jects analysis of thigh circumference showed signifi-
cant differences between moments (F = 257.81,
η ² = 0.87, P < 0.001), while between-subjects analy-
sis did not (F = 0.23, η² = 0.01, P = 0.63), with signifi-
cant interaction (F = 7.77, η² = 0.17, P = 0.008). For
muscle thickness, results were similar; within-sub-
jects analysis showed significant differences between
moments (F = 334.6, η² = 0.90, P < 0.001), while
between-subjects analysis did not (F = 0.22, η² = 0.01,
P = 0.64), with significant interaction (F = 6.83,
Barbalho et al. 5

Table 2.  Anthropometrical responses to passive manipulation and addition of blood flow restriction in intensive
care unit patients.

Group Control (n = 20) Blood flow restriction (n = 20)

  Baseline Absolute Percentage ES Baseline Absolute Percentage ES

mean (SD) change (SD) change (SD) mean (SD) change (SD) change (SD)
Thigh circumference (cm) 48.2 (2.5) –3.6 (1.3)a –7.4 (2.8)a 1.40 48.1 (2.9) –2.5 (1.1)a,b –5.2 (2.2)a,b 0.86
Muscle thickness (mm) 11.2 (2.7) –2.8 (0.7)a –25.4 (6.5)a 1.03 11.2 (2.6) –2.1 (0.9)a,b –18.8 (7.2)a,b 0.80

ES: effect size.

aStatistically different change from baseline (P = 0.001).
bDifferent from the control limb (P = 0.001).

η² = 0.15, P = 0.01). Pairwise comparisons are pre-

sented in Table 2, where it is shown that all pre- to
post-changes were statistically significant
(P < 0.001). In addition, rate of muscle wasting was
6.5% lower when BFR was added to a passive
manipulation protocol and showed lower effect sizes.
Supplemental Figure 1 shows individual
responses to passive manipulation, with and with-
out BFR, for quadriceps muscular thickness and
thigh circumference. All individuals showed lower
muscle wasting in the restricted limb, and losses of
35% were evidenced.
Figure 2 presented correlations between the
length of the intervention for each individual and
percentage changes in quadriceps muscular thick-
ness (Figure 2(a)) and thigh circumference (Figure
2(b)). Significant correlations presented indicate
that longer periods of interventions lead to greater
rate of muscle wasting. It seems that for CTL limb,
muscle loss reached ~20% after 9 days, while for
BFR limb, losses of this magnitude were only evi-
denced after 12 days. No correlations were found
Figure 2.  Correlations between the length of the
between initial body mass and quadriceps muscu- intervention for each individual and percentage
lar thickness changes for BFR (r = 0.17, P = 0.45) changes in quadriceps muscular thickness (a) and thigh
or CTL (r = 0.25, P = 0.28) limbs, which indicates circumference (b).
that total body mass cannot predict muscle loss.
limb showed statistically lower muscle loss in com-
Discussion parison to the limb that received the passive motor
The present study aimed to investigate the effects of physical therapy only.
the addition of blood flow restriction to a passive These findings are due to primary physiological
mobilization protocol on the rate of muscle wasting mechanisms in which occlusion training stimu-
from short-term hospitalization in an intensive care lates anabolic growth through metabolic accumu-
unit. The main results showed that blood flow lation,18 which stimulates subsequent increase
restricted and control group both groups presented of anabolic growth factors,19 when stimulated by
significant muscle wasting; however, the occluded an intramuscular environment.20 In addition to
6 Clinical Rehabilitation 00(0)
recruitment of fast-twitch fibers and increased
protein synthesis through the target pathway of
rapamycin mammalian target of rapamycin
(mTOR),13,21 increased heat shock proteins,22
nitric oxide synthase-1,23 and decreased myostatin
expression were observed.12
Our results are in agreement with other that has
previously been reported with cancer patients in
the intensive care unit,3 which investigated the
percentage of muscle mass loss in patients under
mechanical ventilation, sedation, caloric intake,
and routine physiotherapy care, similar to the pre-
sent study. In a five-day period, the gastrocnemius
reduced its muscular volume between 13.1% and
37.5%, and the quadriceps of 11.2% and 62.7%,3
similar values that we found in the present study.
Although direct comparison cannot be made, it
suggests a similar response in hospitalized elderly
individuals.
Previous studies suggested that immobilization
in bed causes complications such as muscle wasting
and decreased muscle strength, loss of bone mass,
and cardiovascular changes.4,24 Immobility, how-
ever, is not the only determinant of muscle wasting.
In patients hospitalized in intensive care unit, the
loss of muscle mass may also be caused by seda-
tion, reducing protein intake, as well as frequent
infections and sepsis that contribute to muscle
metabolism and, promoting protein catabolism.25,26
Despite this, it is known that muscle is a hormone-
active tissue; thus, the decrease of muscle mass
endangers the metabolism and health of intensive
care unit patients.27
Our findings confirm that the use of blood flow
restriction is an effective strategy in cases of immo-
bilization24 as well as in frail people.10,28 The study
conducted by Hylden et al.28 investigated the blood
flow restriction use in hospitalized patients with
chronic weakness of quadriceps and ischiotibial,
who suffered from traumatic injuries. A low load
(20% one-repetition maximum (1RM)) was used in
knee extension, leg press, and reverse leg press, in
six sessions during two weeks. The results showed
improvement of the torque in isokinetic test from
13% to 37% and average power of 41% to 81%,
depending on the angle and speed of execution,
with total work increased by 35% to 55%. Blood
flow restriction studies are still scarce involving
frail or hospitalized patients.28 To the best of our
knowledge, the present work is the first to investi-
gate the blood flow restriction in an intensive care
unit setting, being a successful innovative proposal
in the attempt to minimize the muscle mass loss,
through motor physiotherapy techniques.
Therefore, we recommend the application of
blood flow restriction in clinical situations in which
the patient cannot perform conventional resistance
training, such as muscular weakness, knee osteoar-
thritis, ligament injuries,29 or coma, as demonstrated
in the present study. Here, we showed that the restric-
tion of blood flow was proven to be superior to the
conventional treatment, as previously suggested.30
We also recommend that application should be based
on the blood pressure of each patient, by using some-
thing around 80% of the arterial blood pressure.
Notwithstanding, the recently widely subjective
method used to induce blood flow restriction, such as
elastic bands, was not investigated here and should
not be encouraged by our findings.
From our design, some limitations should be
considered. First, it was not logistically possible to
blind professionals to apply the intervention.
Second, we only measure muscle thickness of the
quadriceps, and data from the other thigh muscles
should be of interest. Finally, despite we recognize
that our patients’ number is relative small, specific-
ity of situation (coma) and age range (elderly only)
defined as inclusion criteria should be considered.
In fact, we suggest that additional studies could
investigate blood flow restriction effects in a wide
age range population groups, muscle wasting
responses in additional muscles, and follow-up
measurements after sedation period, and investi-
gate the mechanisms of muscle wasting process
and blood flow restriction effects.
Clinical messages
•• Wasting of leg muscles in elderly people
in the intensive care unit was reduced by
restricting blood flow to the leg.
•• Longer immobilization periods were asso-
ciated to a greater rate of muscle wasting.
•• No serious adverse effects were found
from blood flow restriction in this spe-
cific group.
Barbalho et al. 7
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest
with respect to the research, authorship, and/or publica-
tion of this article.
Funding
The author(s) received no financial support for the
research, authorship, and/or publication of this article.
Supplemental Material
Supplemental material for this article is available online.
ORCID iDs
Matheus Barbalho https://orcid.org/0000-0001-7016-
640X
Victor Silveira Coswig https://orcid.org/0000-0001
-5461-7119
References
1. Godoy MDP, Costa HLLS, Neto AES, et al. Muscular
weakness acquired in ICU (ICU-AW): effects of systemic
neuromuscular electrical stimulation. Rev Bras Neurol
2015; 51(4): 110–113.
2. Berg HE, Larsson L and Tesch PA. Lower limb skeletal
muscle function after 6 wk of bed rest. J Appl Physiol
1997; 82: 182–188.
3. Dittmer DK and Teasell R. Complications of immobiliza-
tion and bed rest. Part 1: musculoskeletal and cardiovas-
cular complications. Can Fam Phys 1993; 39: 1428–1437.
4. Nishimura Y, Fukuoka H, Kiriyama M, et al. Bone turno-
ver and calcium metabolism during 20 days bed rest in
young healthy males and females. Acta Physiol Scand
Suppl 1994; 616: 27–35.
5. Müller EA. Influence of training and of inactivity on
muscle strength. Arch Phys Med Rehabil 1970; 51:
449–462.
6. Gosselink R, Bott J, Johnson M, et al. Physiotherapy for
adult patients with critical illness: recommendations of
the European Respiratory Society and European Society
of Intensive Care Medicine Task Force on Physiotherapy
for critically ill patients. Intensive Care Med 2008; 34(7):
1188–1199.
7. Winkelman C, Higgins PA and Chen YJ. Activity in the
chronically critically ill. Dimens Crit Care Nurs 2005;
24(6): 281–290.
8. Llano-Diez M, Renaud G, Andersson M, et al. Mechanisms
underlying ICU muscle wasting and effects of passive
mechanical loading. Crit Care 2012; 16(5): R209.
9. Loenneke JP and Pujol TJ. Kaatsu: rationale for applica-
tion in astronauts. Hippokratia 2010; 14: 224–228.
10. Karabulut M, Abe T, Sato Y, et al. The effects of low-
intensity resistance training with vascular restriction on
leg muscle strength in older men. Eur J Appl Physiol
2010; 108(1): 147–155.
11. Hughes L, Paton B, Rosenblatt B, et al. Blood flow restric-
tion training in clinical musculoskeletal rehabilitation: a
systematic review and meta-analysis. Br J Sports Med
2017; 51: 1003–1011.
12. Kawada S and Ishii N. Skeletal muscle hypertrophy after
chronic restriction of venous blood flow in rats. Med Sci
Sports Exerc 2005; 37: 1144–1150.
13. Fujita S, Abe T, Drummond MJ, et al. Blood flow restric-
tion during low-intensity resistance exercise increases
S6K1 phosphorylation and muscle protein synthesis.
J Appl Physiol 2007; 103: 903–910.
14. Madarame H, Kurano M, Takano H, et al. Effects of low-
intensity resistance exercise with blood flow restriction on
coagulation system in healthy subjects. Clin Physiol Funct
Imaging 2010; 30: 210–213.
15. Takarada Y, Takazawa H, Sato Y, et al. Effects of resist-
ance exercise combined with moderate vascular occlusion
on muscular function in humans. J Appl Physiol 2000;
88(6): 2097–2106.
16. Smith-Ryan AE, Trexler ET and Norton LE. Metabolic
adaptation to weight loss: implications for the athlete. J
Int Soc Sports Nutr 2014; 11(1): 7.
17. Loureiro TR, Guimarães BL, Caldeira JB, et al.
Utilização da escala MRC para avaliação funcional do
paciente crítico após a extubação. Rev Bras Fisioter
2012; 16: 455–455.
18. Gentil P, Oliveira E and Bottaro M. Time under tension
and blood lactate response during four different resistance
training methods. J Physiol Anthropol 2006; 25: 339–344.
19. Takarada Y, Nakamura Y, Aruga S, et al. Rapid increase
in plasma growth hormone after low-intensity resistance
exercise with vascular occlusion. J Appl Physiol 2000; 88:
61–65.
20. Victor RG and Seals DR. Reflex stimulation of sympa-
thetic outflow during rhythmic exercise in humans. Am J
Physiol 1989; 257: H2017–H2024.
21. Wang X and Proud CG. The mTOR pathway in the con-
trol of protein synthesis. Physiology (Bethesda) 2006; 21:
362–369.
22. Senf SM, Dodd SL, McClung JM, et al. Hsp70 over
expression inhibits NF-kappaB and Foxo3a transcrip-
tional activities and prevents skeletal muscle atrophy.
FASEB J 2008; 22: 3836–3845.
23. Anderson JE. A role for nitric oxide in muscle repair:
nitric oxide-mediated activation of muscle satellite cells.
Mol Biol Cell 2000; 11: 1859–1874.
24. Teasell R and Dittmer DK. Complications of immobiliza-
tion and bed rest. Part 2: other complications. Can Fam
Phys 1993; 39: 1440–1446.
25. Preiser JC, Van Zanten ARH, Berger MM, et al. Metabolic
and nutritional support of critically ill patients: consensus
and controversies. Crit Care 2015; 19: 35.
26. Port AM and Apovian C. Metabolic support of the obese
intensive care unit patient: a current perspective. Curr
Opin Clin Nutri Metab Care 2010; 13(2): 184–191.
8 Clinical Rehabilitation 00(0)

27. Koukourikos K, Tsaloglidou A and Kourkouta L. Muscle
atrophy in intensive care unit patients. Acta Inform Med
2014; 22(6): 406–410.
28. Hylden C, Burns T, Stinner D, et al. Blood Flow restric-
tion rehabilitation for extremity weakness: a case series. J
Spec Oper Med 2015; 15(1): 50–56.
29. Slysz J, Stultz J and Burr JF. The efficacy of blood flow
restricted exercise: a systematic review & meta-analysis.
J Sci Med Sport 2016; 19: 669–675.
30. Patterson SD, Hughes L, Head P, et al. Blood flow restriction
training: a novel approach to augment clinical rehabilitation:
how to do it. Br J Sports Med 2017; 51(23): 1648–1649.