Original Paper

Cerebrovasc Dis 2014;37:401–408 Received: November 27, 2013

Accepted: March 31, 2014
DOI: 10.1159/000362533
Published online: June 28, 2014

Head Position and Cerebral Blood Flow

Velocity in Acute Ischemic Stroke:
A Systematic Review and Meta-Analysis
Verónica V. Olavarría a, c Hisatomi Arima e Craig S. Anderson e, g Alejandro M. Brunser b
Paula Muñoz-Venturelli b, e Stephane Heritier f Pablo M. Lavados a, d
a
Vascular Neurology and b Neurosonology Laboratory, Neurology Service, Department of Medicine and
c
Department of Critical Care, Clínica Alemana de Santiago, Universidad del Desarrollo, and d Department of Neurological
Sciences, Universidad de Chile, Santiago, Chile; e Neurological and Mental Health Division at f The George Institute for
Global Health, Sydney Medical School, University of Sydney, and g Department of Neurology, Royal Prince Alfred Hospital,
Sydney, N.S.W., Australia

Key Words
Stroke · Blood flow velocity · Transcranial Doppler
ultrasonography · Head position · Meta-analysis
Abstract
Background: Patients with acute ischemic stroke (AIS) have
impaired vasomotor reactivity, especially in the affected ce-
rebral hemisphere, such that they may depend directly on
systemic blood pressure to maintain perfusion to vulnerable
‘at risk’ penumbral tissue. As the sitting up position may af-
fect cerebral perfusion by decreasing cerebral blood flow
(CBF) in salvageable tissue, positioning AIS patients with
their head in a lying flat position could increase CBF through
collateral circulation or gravitational force. We wished to
quantify the effect of different head positions on mean flow
velocity (MFV) by transcranial Doppler ultrasonography
(TCD) in AIS patients to assess the potential for benefit (or
harm) of head positioning in a clinical trial. Methods: We per-
formed a systematic review and meta-analysis of observa-
tional studies with TCD to evaluate differences in cerebral
MFV between the lying flat and sitting up head positions in
AIS. For each study and each comparison, we obtained the
mean value of changes in MFV and its variance. Results: A
total of 303 studies were identified, but 298 were excluded
for varying reasons; 4 papers met the inclusion criteria and
57 patients were included in the meta-analysis for calcula-
tion of the overall mean difference in MFV. We found a sig-
nificant increase in MFV from a bed angle of 30 to 15° (4.6
cm/s, 95% confidence interval, CI, 2.9–6.2, p < 0.001) and
from 30 to 0° (8.3 cm/s, 95% CI 5.3–11.3, p < 0.001) in the af-
fected hemisphere but not on the normal side in AIS pa-
tients. Conclusions: In AIS patients, MFV increased signifi-
cantly in the side affected by the stroke but not in the unaf-
fected side when they were positioned in a lying flat head
position at 0 or 15° compared to an upright head position at
30°. The clinical significance of these findings is now under-
going further randomized evaluation in the international
multicenter Head Position in Acute Stroke Trial (HeadPoST).
© 2014 S. Karger AG, Basel
Introduction
Patients with acute ischemic stroke (AIS) have im-
paired autoregulation or vasomotor reactivity, especially
in the affected hemisphere, such that they may depend di-
rectly on systemic blood pressure (BP) to maintain perfu-

© 2014 S. Karger AG, Basel Pablo M. Lavados, MD, MPH

1015–9770/14/0376–0401$39.50/0 Vascular Neurology, Department of Medicine, Clínica Alemana de Santiago
Av. Manquehue Norte, 1410, Piso 10
E-Mail karger@karger.com
Santiago 7650567 (Chile)
www.karger.com/ced
E-Mail pablolavados @ yahoo.com
Table 1. Quality of the selected studies
Study Study design
Wojner et al. [20], 2002 prospective, nonrandomized
Schwarz et al. [19], 2002 prospective, nonrandomized
Wojner-Alexander et al. [18], 2005 prospective, nonrandomized
Hunter et al. [17], 2011 prospective, nonrandomized
sion to vulnerable ‘at risk’ penumbral tissue [1, 2]. Further-
more, vasomotor reactivity could be further impaired in
patients that have worse prognosis such as diabetics [3, 4].
However, except for the Japanese, most guidelines recom-
mend patients should be positioned with their heads in a
sitting up position after AIS or make no recommendation
at all, and to commence mobilization as soon as possible
after admission to hospital [4–9]. A sitting up position may
affect cerebral perfusion by decreasing cerebral blood flow
(CBF) in salvageable tissue in AIS patients with impaired
vasomotor reactivity [10]. Conversely, positioning pa-
tients with AIS with their head in a lying flat position could
be less orthostatically challenging and improve outcomes,
but supporting data are limited and contradictory [11–14].
A recent preclinical study showed that in mice with bilat-
eral common carotid artery occlusion, tilting of the head
to –5° (Trendelenburg position) increased CBF signifi-
cantly in both hemispheres compared to keeping the head
at 0° [15]. A systematic review concluded that there was an
equivocal effect of body position on CBF and other mea-
sures of physiological homeostasis in patients with AIS
[16]. An underlying hypothesis generated by several small
observational studies that have used transcranial Doppler
ultrasonography (TCD) after AIS (affecting the anterior
circulation) is that passive vasodilatation occurs in the
ischemic tissue, so an increase in cerebral mean flow veloc-
ity (MFV) in the lying flat position due to gravitational
force and/or recruitment of collateral vessels could in-
crease residual CBF [17, 18]. We undertook a systematic
review with meta-analysis to quantify the effect of different
head positions on MFV measured by TCD in patients with
AIS and determined the potential mechanisms for benefit
(or harm) of randomizing to bed position in a clinical trial.
Methods
Search Strategy
We conducted a systematic electronic search of Ovid/MED-
LINE and PubMed/MEDLINE, and hand searched references
402 Cerebrovasc Dis 2014;37:401–408
DOI: 10.1159/000362533
Eligibility Diagnostic method and meas- Offline blinded
criteria stated ure of main outcome specified assessment of MFV
yes yes not stated
yes yes not stated
yes yes not stated
yes yes yes
from relevant clinical papers published from 1946 to October
2013. The search strategy included relevant text words and medical
subject headings that included all spellings of ‘stroke’, ‘head posi-
tion’ and ‘head posture’. The search was limited to human studies
but without language restriction.
Eligibility Criteria
Inclusion criteria were the following: original articles on AIS,
prospective design studies (clinical trials, experimental prospec-
tive clinical series and cohort studies) and available data on MFV
in the middle cerebral arteries (MCA) in different positions mea-
sured by TCD in patients with AIS of less than 48 h. Exclusion
criteria were as follows: retrospectives studies, single case reports,
diagnostic test evaluations, letters to the editor, opinion papers,
studies without MVF evaluation or TCD data, and duplicate stud-
ies.
Study Selection and Data Extraction
The list of studies identified was independently assessed by two
stroke neurologists (V.V.O. and P.M.-V.) who made a decision on
the eligibility for inclusion. Initially, they screened titles/abstracts
and then made a full-text assessment of the papers based on eligi-
bility. Information on changes in MFV of MCA associated with
head position change, average MFV of MCA at each head position
and their variances on the affected and unaffected sides at 30, 15
and 0° was retrieved from the included studies. The quality of the
studies was assessed using the criteria described in table 1.
Statistical Analysis
For each study and each comparison, we obtained the mean
value of changes in MFV and its variance. Although variance of the
mean difference in MFV was not reported in 2 of the studies [19,
20], we estimated it using variance in MFV at each head position
and the rho value of 0.8, which was conservatively defined based
on the rho values in the other 2 studies (range 0.88–0.99) [17, 18].
Overall estimates of effect and 95% confidence intervals (CI) were
calculated using a random-effects model and inverse variance
weighting (weighting by the precision of the estimate in each
study). Analyses were stratified by the side of the cerebral infarc-
tion (ipsilateral or contralateral). Consistency of effects across
studies was tested using the χ2 test of homogeneity. The percentage
of variability across studies attributable to heterogeneity beyond
chance was estimated using the I2 statistic. Substantial heterogene-
ity was determined as a value greater than 50%. Potential publica-
tion bias was assessed using the Egger test and represented graph-
ically using Begg funnel plots of the natural log of the RR versus its
standard error. STATA (release 12.0; Stata Corporation, College
Olavarría /Arima /Anderson /Brunser /
Muñoz-Venturelli /Heritier /Lavados
 Literature search retrieved articles
for abstract/title screening
n = 303

Articles excluded n = 298

Reasons for exclusion:
Reviews = 12
Case reports = 11
Diagnostic test = 20
Letters to the editor = 7
Duplicated articles = 15
Position and stroke without MFV measure = 13
Rehabilitation = 64
Physiology = 17
Position and hemodynamics without stroke = 78
Others = 61

Selected articles for full

text assessment
n=5

Articles excluded from meta-analysis of MFV = 1

Reasons for exclusion:
No TCD evaluation = 1

Articles selected for

MFV meta-analysis
n=4
Fig. 1. Flow diagram of article selection and
progress through the systematic review.

Station, Tex., USA) was used for estimation of the effects of head
position change.
The results are reported according to the checklist proposed by
the Meta-analysis of Observational Studies in Epidemiology
(MOOSE) Group [21].
Results
A total of 303 studies met the search criteria and were
screened, of which 298 were excluded for varying reasons
(fig. 1). Only 5 studies evaluated MFV in different posi-
tions after AIS and were included; one of them was ex-
cluded because it used single-photon emission computed
tomography to measure CBF. Finally, inclusion criteria
were met by 4 nonrandomized studies, of which 3 inves-
tigated MFV both on the side affected and unaffected by
stroke [17, 19, 20] and 1 reported MFV only on the af-
fected side [18]. The study year, number of patients, time
from symptom onset to TCD, bed angle and outcome in
these 4 studies are summarized in table 2. The studies, in
chronological order, were as follows:
(1)A prospective study on 11 selected patients with ante-
rior circulation AIS and extra- or intracranial occlu-
sion, in whom MFV was measured in the ipsilateral
and contralateral MCAs by a nonblinded observer.
The patients were positioned at 30, 15 and 0°. The au-
thors found a nonsignificant 13% increase in MFV
when the patients were positioned from 30 to 0° and a
significant increase of 9.2% from 30 to 15° [20].
(2)A study that included 18 consecutive patients with large
hemispheric infarction who were monitored by a non-
blinded observer with TCD while their position was
changed from 0 to 15 and 30°. These patients were in-
tubated, ventilated, sedated and had continuous neu-
romonitoring, with their cerebral perfusion pressures
kept at ≥70 mm Hg. To be included, patients had to be
stable (no modification of ventilator parameters, fluid
therapy or medications) for at least 2 h and to have no

Head Position and Cerebral Blood Flow Cerebrovasc Dis 2014;37:401–408 403
Velocity in Stroke DOI: 10.1159/000362533
Table 2. Studies on the effect of head position on MFV in patients with acute ischemic stroke

Study Patients, n Time since Intervention Findings

symptom onset

Wojner et al. [20], 11 <48 h 30, 15 and 0° position significant increase in MFV from 30 to 15° and
2002 significant increase in MFV from 30 to 0°
Schwarz et al. [19], 18 <6 days 30, 15 and 0° position significant decrease in MFV from 0 to 15° and
2002 then to 30°
Wojner-Alexander et al. [18], 20 <24 h 30, 15 and 0° position significant increase in MFV from 30 to 15° and
2005 from 30 to 0°
Hunter et al. [17], 8 <24 h 30, 15 and 0° position significant increase in MFV from 30 to 0° in
2011 patients who did not recanalize

evidence of increased intracranial pressure. MFV both
in the ipsilateral and contralateral MCAs decreased
significantly when patients were elevated from 0 to 15°
and then to 30°. Interestingly, cerebral perfusion pres-
sure was highest at 0° due to increased mean arterial
pressure [19].
(3)A prospective study of 20 selected patients with ante-
rior circulation infarction, persistent arterial occlusion
and residual arterial flow examined with TCD within
24 h of symptom onset only in the ipsilateral side of
stroke. Measurements of MFV in the affected MCA
were made unblinded at 30, 15 and 0°. The authors re-
ported an average increase of 20% of MFV when the
patients were tilted from 30 to 0° [18].
(4)A prospective study of 8 patients with anterior circula-
tion ischemic strokes stratified according to recanali-
zation by angiography, whose MFV were measured
offline by a blinded observer at a 30, 15 and 0° position.
The study showed a significant increase in MFV in the
affected territory in patients who had not recanalized
when they were at 0° compared to 30°, but not in pa-
tients with recanalization [17].
The meta-analysis included 57 patients and showed a
significant increase in MFV, from 30° to 0° (mean differ-
ence 8.3 cm/s, 95% CI 5.3–11.3, p < 0.001) and from 30 to
15° (mean difference 4.6 cm/s, 95% CI 2.9–6.2, p < 0.001)
in the side affected by stroke (fig. 2). There was no vari-
ability across studies attributable to heterogeneity beyond
chance (I2 = 0, p > 0.5, both from 30 to 15° and from 30
to 0° positioning). In the unaffected side, there was no
significant increase in MFV from 30 to 15° (mean differ-
ence 1.7 cm/sec, 95% CI –3.98 to 7.29, p < 0.47) or from
30 to 0° (mean difference 3.6 cm/s, 95% CI –3.1 to 10.3,
p < 0.3; fig. 3). There was significant heterogeneity in this
subgroup (I2 = 84%, p < 0.01). Formal statistical testing
showed no obvious evidence of publication bias (p > 0.05)
except for the position change from 30 to 0° on the unaf-
fected side (p = 0.02; fig. 4).
Discussion
In this systematic review and meta-analysis of obser-
vational studies, we found that in patients with AIS, MFV
significantly increased in the side affected by the stroke
but not in the unaffected side when they were positioned
in the lying flat head position at 0 or 15° compared to the
upright head position at 30°.
There are various possible mechanisms for this in-
crease in MFV. They could be related to the effect of grav-
itational force acting on passively dilated vessels in the
ischemic territory, thus increasing the pressure gradients
and residual blood flow [18]. It is also possible that the
lying flat head position could produce an improved use
of collateral circulation to the ischemic penumbra region,
especially in patients who have not adequately recana-
lized either spontaneously or through thrombolysis [22].
This increase in leptomeningeal collateral use has been
shown to predict the extent of radiological and clinical
outcomes in anterior circulation infarction and includes
both pial and lenticulostriatal arteries distal to M1 or in-
tracranial ICA occlusions [23]. Even though this hypoth-
esis is attractive, it is as yet unproven, as the data on in-
traluminal MFV increase measured by TCD did not
quantify collateral flow. The effect of BP changes due to
orthostatism and its relationship with increased MFV is
equivocal and could be important only in large hemi-
spheric infarctions; this can be deduced from the data of
3 studies where the BP did not change or was not associ-
ated with changes in MVF [17, 18, 20], while in the study

404 Cerebrovasc Dis 2014;37:401–408 Olavarría /Arima /Anderson /Brunser /

       

DOI: 10.1159/000362533 Muñoz-Venturelli /Heritier /Lavados

     
 Mean difference

From 30 to 15°
Schwarz et al. [19], 2002 6.00 (–5.56 to 17.56)
Wojner et al. [20], 2002 5.00 (–1.27 to 11.27)
Wojner-Alexander et al. [18], 2005 4.80 (3.04 to 6.56)
HOBOE study [17], 2011 1.10 (–4.98 to 7.18)
Overall 4.57 (2.95 to 6.19)
Homogeneity: χ2 = 1.40, d.f. = 3 (p = 0.71), I2 = 0%
Test of overall effect: Z = 5.54 (p < 0.001)

From 30 to 0°
Schwarz et al. [19], 2002 11.60 (–1.73 to 24.93)
Wojner et al. [20], 2002 7.00 (0.14 to 13.86)
Wojner-Alexander et al. [18], 2005 8.20 (4.67 to 11.73)
HOBOE study [17], 2011 11.30 (–1.64 to 24.24)
Overall 8.31 (5.34 to 11.28)
Homogeneity: χ2 = 0.58, d.f. = 3 (p = 0.90), I2 = 0%
Test of overall effect: Z = 5.48 (p < 0.001)

–10 0 10 20 30
Mean difference (cm/s)

Fig. 2. Effects of head position change on MFV of MCA on the af-
fected side: meta-analysis of 4 observational studies using TCD in
acute ischemic stroke. For each study and each comparison, the
mean difference in MFV was estimated, with overall estimates of
effect and 95% CI calculated using a random-effects model and
inverse variance weighting. Boxes and horizontal lines represent
mean difference and 95% CI for each trial; size of boxes is propor-
tional to the inverse of variance of the trial results. Diamonds show
95% CI for pooled estimates of effect and are centered on pooled
mean difference. HOBOE study = Head-of-Bed Optimization of
Elevation study.

Mean difference

From 30 to 15°
Schwarz et al. [19], 2002 1.70 (–3.01 to 6.01)
Wojner et al. [20], 2002 7.00 (2.10 to 11.90)
HOBOE study [17], 2011 –2.60 (–4.95 to –0.25)
Overall 1.66 (–3.98 to 7.29)
Homogeneity: χ2 = 12.80, d.f. = 2 (p = 0.002), I2 = 84%
Test of overall effect: Z = 0.58 (p = 0.47)

From 30 to 0°
Schwarz et al. [19], 2002 3.70 (–0.81 to 8.21)
Wojner et al. [20], 2002 10.00 (4.32 to 15.68)
HOBOE study [17], 2011 –2.10 (–5.63 to 1.43)
Overall 3.57 (–3.15 to 10.30)
Homogeneity: χ2 = 13.34, d.f. = 2 (p = 0.001), I2 = 85%
Test of overall effect: Z = 1.04 (p = 0.30)
–10 0 10 20 30
Mean difference (cm/s)

Fig. 3. Effects of head position change on MFV of MCA on the unaffected side: meta-analysis of 3 observational studies using TCD in
acute ischemic stroke (see also legend to figure 2 above).

Head Position and Cerebral Blood Flow Cerebrovasc Dis 2014;37:401–408 405
Velocity in Stroke DOI: 10.1159/000362533
 0 0

Standard error

Standard error
2
4
4
6

6 8

–5 0 5 10 15 –5 0 5 10 15 20
a Mean difference (cm/s) b Mean difference (cm/s)

0 0

0.5
Standard error

Standard error
1
1.0

1.5
2
2.0

2.5 3

–5 0 5 10 –5 0 5 10
c Mean difference (cm/s) d Mean difference (cm/s)

Fig. 4. Begg’s funnel plot for the assessment of publication bias in studies examining the effects of position change
on MFV. Egger’s test: p = 0.66 for position change from 30 to 15° on the affected side (a), p = 0.34 for position
change from 30 to 0° on the affected side (b), p = 0.23 for position change from 30 to 15° on the unaffected side
(c) and p = 0.02 for position change from 30 to 0° on the unaffected side (d).

by Schwarz et al. [19] there was a marked decrease in BP
when the head of the patients was elevated. It is also pos-
sible that this position produces an increase in cardiac
output, as seen in studies of healthy young male subjects
whose heart rate decreased slightly but whose stroke vol-
ume and cardiac output increased significantly with un-
changed BP and decreased left ventricular ejection when
tilted from an upright to a lying flat position [24, 25].
The significant increase of MFV in the affected side
and not in the unaffected side could be explained by the
fact that vasomotor reactivity is more frequently impaired
in the side of the ischemic lesion, as has been reported in
studies using TCD [26, 27]. In this scenario, distal passive
vasodilatation in the affected side would require local per-
fusion pressure gradients to produce blood flow – a con-
dition created by the flat head position. It is also possible
that this was due to chance as only 3 studies and fewer
patients were included in this analysis.
There are limitations to our study which could be a
potential source of bias. The quality of the selected studies
was generally low as they included nonconsecutive select-
ed samples of AIS patients, the head position was not ran-
domized and outcome (MFV by TCD) evaluations were
not masked to the position of the patients in 3 of 4 studies.
The studies were small and no clinical outcomes were re-
ported. There was heterogeneity in the results of MFV in
the unaffected hemisphere, which may be explained by
the study of Hunter et al. [17] who found a nonsignificant
trend towards a decrease in MFV in the side unaffected
by stroke. Another limitation is that all data come from
large vessel infarction in the anterior circulation, leaving
out evidence on small vessel or posterior circulation isch-
emic stroke. Even though we did not detect any publica-
tion bias, the power to detect it was limited as only 3 of 4
studies were available for an analysis of MVF in the unaf-
fected side.

406 Cerebrovasc Dis 2014;37:401–408 Olavarría /Arima /Anderson /Brunser /

       

DOI: 10.1159/000362533 Muñoz-Venturelli /Heritier /Lavados

     
 Although MFV does not equate CBF but reflects it,
there remains uncertainty over any increase in MFV from
different head positions in AIS and, if it were so, over the
relevance of this to potentially beneficial clinical out-
comes and adverse events such as aspiration pneumonia
[28, 29], worsening cardiac failure, increasing brain swell-
ing and intracranial hypertension [30] or a delay in early
mobilization [31]. This is an area of uncertainty and lack
of evidence.
Recently, a low 4.5% incidence of pneumonia observed
in patients lying flat after thrombolysis attributable to the
position was presented at the European Stroke Confer-
ence in London in 2013, concluding that avoiding this
position due to concerns about subsequent pneumonia
may be unjustified [32]. Furthermore, the definition of
early mobilization is unclear and could be harmful in the
first 24 h [13]. The timing and duration of the flat head
position is also a matter of concern, especially in large
hemispheric infarction. The data from Schwarz et al. [19]
showed that intracranial pressure was higher at 15 and 0°
than at 30° and that even though cerebral perfusion pres-
sure was unchanged, after 48 h of symptom onset in a
large infarction where brain swelling is expected to rise,
changes in head position should be restricted. The evi-
dence of potential benefit is substantial enough to pro-
ceed to evaluations in a large-scale randomized clinical
trial, as is being done in the HeadPoST trial.
Acknowledgments
The George Institute for Global Health and the Clínica Ale-
mana de Santiago provided funding for the study.
Disclosure Statement
Dr. V.V. Olavarría has received travel funding from Boehring-
er Ingelheim. She also receives institutional support from Clínica
Alemana for clinical research, and research support from The
George Institute for Global Health.
Professor H. Arima is a recipient of a future fellowship from the
Australian Research Council.
Professor C.S. Anderson is supported by a Senior Principal Re-
search Fellowship.
Dr. A.M. Brunser receives institutional support from Clínica
Alemana for clinical research. He also performs TCD studies (20%
effort) and bills for this procedure.
Dr. P. Muñoz-Venturelli is a recipient of an educational schol-
arship from Clínica Alemana.
Professor S. Heritier reports no disclosures.
Dr. P.M. Lavados served on a scientific advisory board for Bris-
tol Meyers Squibb. He receives grant support from Lundbeck Chile
and AstraZeneca and has received funding for travel from Bayer
and Boehringer Ingelheim. He also performs TCD studies (5% ef-
fort) and bills for this procedure. He receives research support
from The George Institute for Global Health.

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