Autonomic Shift and Increased Susceptibility to Infections

After Acute Intracerebral Hemorrhage

Marek Sykora, MD, PhD; Jennifer Diedler, MD; Sven Poli, MD; Timolaos Rizos, MD;
Peter Turcani, MD, PhD; Roland Veltkamp, MD; Thorsten Steiner, MD

Background and Purpose—High infection rate after severe stroke may partly relate to brain-induced immunodepression
syndrome. However, the underlying pathophysiology remains unclear. The aim of the current study was to investigate
the role of autonomic shift in increased susceptibility to infection after acute intracerebral hemorrhage (ICH).
Methods—We retrospectively analyzed 62 selected patients with acute ICH from our prospective database. Autonomic
shift was assessed using the cross-correlational baroreflex sensitivity (BRS). The occurrence and cause of in-hospital
infections were assessed based on the clinical and laboratory courses. Demographic and clinical data including initial
stroke severity, hemorrhage volume, intraventricular blood extension, history of aspiration, and invasive procedures
such as mechanical ventilation, surgical hematoma evacuation, external ventricular drainage, central venous and urinary
catheters, and nasogastric feeding were recorded and included in the analysis.
Results—We identified 36 (58%) patients with infection during the first 5 days of hospital stay. Patients with infections
had significantly lower BRS, higher initial NIHSS scores, larger hemorrhages, and more frequently had intraventricular
blood extension and underwent invasive procedures. In the multivariate regression model, decreased BRS (OR, 0.54;
95% CI, 0.32– 0.91; P⫽0.02) and invasive procedures (OR, 2.32; 95% CI, 1.5–3.6; P⬍0.001) remained independent
predictors for an infection after ICH.
Conclusions—Decreased BRS was independently associated with infections after ICH. Autonomic shift may play an
important role in increased susceptibility to infections after acute brain injury including ICH. The possible therapeutic
relevance of autonomic modulation warrants further studies. (Stroke. 2011;42:1218-1223.)
Key Words: autonomic 䡲 baroreflex 䡲 intracerebral hemorrhage 䡲 infection 䡲 stroke 䡲 sympathetic

A cute stroke is associated with increased susceptibility to

bacterial infection. Pulmonary and urinary infections are
the most frequent medical complications after stroke and the
leading cause of death, with prevalences of up to 33%.1 The
pathophysiological mechanisms leading to high occurrence of
infections after stroke are not fully understood. Poststroke
pneumonia may result from aspiration caused by impaired
consciousness or reduced bulbar reflexes with consecutive
oropharyngeal dysphagia, as well as from invasive measures
such as feeding tube placement or orotracheal intubation and
mechanical ventilation.2 However, aspiration and specific
neurological impairments alone do not completely explain the
high incidence of poststroke infections.3 There is increasing
evidence that brain–immune interactions become dysregu-
lated after stroke, resulting in a stroke-related immunosup-
pression syndrome.4 Animal models of stroke and research in
humans have well-documented stroke-induced immunodefi-
ciency mediated via hypothalamic–pituitary axis and sympa-
thetic nervous system activation.5 Catecholamine-mediated
impairment of cellular immune responses include lymphopenia,
decreased lymphocyte activation, shift from Th1 to Th2 cytokine
predominance, or decreased HLA- DR expression on mono-
cytes.6 – 8 Recently, suppressed neutrophil respiratory burst
strongly correlated with catecholamine levels in subjects with
hemorrhagic stroke.9 Accordingly, enhanced sympathetic activ-
ity with subsequent suppressed immune function has been
associated with the occurrence of poststroke infections.7,10
Baroreflex sensitivity (BRS) is an established and reliable
parameter to quantify the balance of autonomic nervous
system noninvasively and has been clinically proven in
numerous studies.11–13 Decreased BRS depicting sympathetic
activation has been repeatedly found in acute ischemic and
hemorrhagic stroke patients and is related to unfavorable
outcome.11,14 Hence, we aimed to investigate if BRS mea-
sured on admission may predict the occurrence of in-hospital
infections after acute hemorrhagic stroke.
Subjects and Methods
Population
From 2007 to 2010, 529 patients with acute intracerebral hemorrhage
(ICH) admitted to our stroke unit or neurological intensive care unit
(ICU) were screened for inclusion into an open prospective database.

Received October 4, 2010; accepted November 26, 2010.

From the Department of Neurology (M.S., J.D., S.P., T.R., R.V., T.S.), University of Heidelberg, Heidelberg, Germany; Department of Neurology
(M.S., P.T.), Comenius University, Bratislava, Slovakia.
Correspondence to Marek Sykora, MD, PhD, Department of Neurology, University Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg,
Germany. E-mail marek.sykora@med.uni-heidelberg.de
© 2011 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.110.604637

Downloaded from http://stroke.ahajournals.org/

1218 by guest on April 14, 2016
 Sykora et al
This database prospectively collected consecutive patients with acute
stroke meeting the criteria for nonbiased measurement of BRS as
follows: at the time of the BRS measurement, all subjects had to be
free of antihypertensive therapy or cardiovascular active treatment
for at least 24 hours (except from urapidil). The type of previous
antihypertensive therapy has been noted. Patients treated for acute
hypertension on admission using bolus administration of parenteral
urapidil, according to our local hospital protocol, were included and
the use of urapidil was noted. The time delay between urapidil
administration and BRS measurement had to be at least 1 hour. The
urapidil use has not been defined as an exclusion criterion because it
has been shown previously that it does not influence the baroreflex
sensitivity when administered acutely.15
Patients with a history of stroke, atrial fibrillation, myocardial
infarction, diabetes mellitus, chronic renal failure, or other medical
conditions known to affect autonomic functions are excluded from
the BRS measurements, because these conditions may confound the
results. For the purposes of the recent study, we retrospectively
analyzed patients from the aforementioned database who fulfilled the
following criteria: (1) acute ICH; (2) BRS measurement within the
first 24 hours after onset of symptoms; and (3) no clinical or
laboratory signs of infection on admission. At the time of the recent
analysis, the database counted 67 patients with ICH. Two patients
were excluded from the further analysis because of early mortality
and 3 were excluded because of probable infection at admission
(C-reactive protein [CRP] ⬎50 mg/L). Thus, 62 patients entered the
final analysis.
The diagnosis of ICH was confirmed by CT or MRI. The ICH
volume was calculated from the first CT or MRI scan using the
a⫻b⫻c⫻0.5 method, as described previously.16 For irregular shapes,
the alternative formula a⫻b⫻c⫻0.33 was used.17,18 Additionally,
the presence of intraventricular hemorrhage was recorded and scored
using the LeRoux score. In this score, each ventricle is graded
separately as: 1, trace of blood; 2, less than half the ventricle filled
with blood; 3, more than half the ventricle filled with blood; and 4,
ventricle filled with blood and expanded, resulting in maximum
score of 16.19 At admission, patients were scored according to the
NIHSS. History of hypertension and previous antihypertensive
therapy was noted and included in the analysis. Demographic and
basic clinical parameters were recorded.
Clinical Management
After BRS measurement at admission, uniform general management
according to local guidelines was applied. This included close
telemetric monitoring of blood pressure and treatment of hyperten-
sion using parenteral infusion of urapidil, clonidine, metoprolol, or
dihydralazine to achieve blood pressure values ⬍160/90 mm Hg.
Orotracheal intubation and ventilatory support was initiated in
patients with a Glasgow Coma Scale score ⬍8. In case of concom-
itant ventricular hemorrhage, placement of an external ventricular
drain was performed. Hematoma evacuation was performed based on
individual consensus between neurointensivist and neurosurgeon in
patients with lobar superficial hematomas or in those deteriorating
clinically. All patients requiring ventilatory support received central
venous catheters, urinary catheters, and nasogastric tubes. Blood
samples were taken on a daily basis, including leukocyte count and
CRP. Body temperature was checked hourly or continuously in the
ICU and at least 3 times per day on the stroke unit. Urine analysis
and bacterial analysis of sputum was performed regularly twice per
week, even if no clinical infection was suspected. In case of suspect
clinical infection, chest radiographs, urine, blood, and sputum
cultivations were performed. Antibiotic treatment was initiated if
infection was clinically, radiologically, and laboratory confirmed
and/or if fever ⬎38.5°C, leukocytosis ⬎12/nL, and CRP ⬎50 mg/L
were present in absence of a clear clinical focus.
Assessment of Infection
The charts and laboratory results have been reviewed up to 5 days
(120 hours) after admission to identify infection. Recorded variables
included presence of clinical signs of infections, CRP values on
admission, leukocyte count and temperature on admission, the
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Automic Shift and Infections After ICH 1219
highest CRP value, leukocyte count and temperature within the first
5 days after admission, urine screening, chest radiographs, and
antibiotic treatment. Based on the results, patients were classified
into 4 groups as described previously.20 The first group included
patients with pneumonia; diagnosis was based on clinical criteria
including fever, purulent sputum, or respiratory deterioration and
positive chest radiographs in combination with laboratory findings of
leukocytosis and CRP ⬎50 mg/L.21,22 The second group comprised
patients with urinary tract infections diagnosed based on elevated
leukocyte count and positive nitrite in the urine screening in
combination with leukocytosis and CRP ⬎50 mg/L. Because of high
frequency of antibiotic treatment, we did not apply a positive urine
culture as criterion.23 Patients who had empirical antibiotic treatment
because of clinically suspected infection with elevated leukocyte
count, CRP ⬎50 mg/L, and fever but without clearly identified focus
during clinical follow-up were classified as being in the third group.
The last group included patients without clinical and laboratory signs
of infection during the first 5 days of hospital stay. Additionally,
surgical evacuation of hematoma, external ventricular drain place-
ment, the history of aspiration, ICU stay, mechanical ventilation,
central venous and urinary catheters, nasogastric tube use, and
antibiotic treatment in first 5 days of hospitalization were recorded.
Because of the high colinearity between variables as ICU stay,
mechanical ventilation, invasive catheters, and surgical treatment,
we recomputed these variables for further analysis into an “invasive-
ness” score, giving 1 point for each procedure, including ICU stay,
mechanical ventilation, central venous catheter, urinary catheter,
nasogastric tube, external ventricular drain placement, and surgical
removal of hematoma.
Assessment of Spontaneous BRS
Blood pressure for spontaneous BRS assessment was measured
noninvasively using the Finometer device (FMS; Finapres Medical
Systems BV). This device uses a volume clamp method to capture
beat-to-beat (continuous) values of blood pressure and pulse rate in
the finger artery. A cuff of appropriate size was attached to the
middle finger of the nonhemiparetic hand of the patient in supine
position and the hand was maintained at heart level. Using the
Finometer device, continuous blood pressure and pulse rate for BRS
assessment were recorded within 24 hours after stroke onset, usually
on admission, for a period of 10 minutes. BRS was calculated using
the sequential cross-correlation method.24 This method calculates the
cross-correlations between a 10-second series of continuous systolic
blood pressure and a 10-second series of interbeat intervals delayed
by 0, 1, 2, 3, 4 and 5 seconds. The delay giving the highest
correlation between the change in systolic blood pressure and the
change in interbeat interval is selected if significant at a preset level
(P⫽0.01). Then, the regression slope is recorded as 1 BRS value.
Subsequently, the process is repeated for series of systolic blood
pressure and interbeat interval samples 1 second later. BRS gain
values were expressed in ms/mm Hg.
Ethics
The local ethics committee approved the study. All patients or their
next of kin gave written informed consent.
Statistics
Distribution of the data was visualized using histograms and tested
using the 1-sample Kolmogorov-Smirnov test. For normally distrib-
uted data, the results are presented as mean, range, and SD; for
non-normally distributed data, results are presented as median,
range, and IQR. For comparison between the groups Fisher test,
Mann–Whitney U test, or Student unpaired t test was used, as
appropriate. Correlation analysis using Spearman or Pearson corre-
lation coefficient was used to explore the univariate associations
between the variables. Partial correlations and multivariate regres-
sions were used to adjust for possible confounders. When significant
in the univariate analysis, variables entered a stepwise logistic
regression model to study the relationship between predictive vari-
ables and dependent variable as follows. A stepwise regression
1220 Stroke May 2011

Table 1. Demographic, Clinical, and Neuroradiological patients (42%) and hematoma was surgically removed in 16
Characteristics of the ICH Population (25.8%). Twenty-nine patients were treated in the stroke unit.
N 62 Of those, 3 (10.3%) received central venous catheters, 14
(48.3%) received urinary catheters, and 4 (13.8%) received
Age (years), mean (range; SD) 61.5 (17–86; 15.8)
nasogastric tubes. Sixteen (26%) patients had a history
Male 32 (51.6%)
suspect of aspiration. The median of the invasiveness score
Etiology was 4 (range, 0 –7; IQR, 5.25). Thirty-six (58%) patients had
Hypertensive 36 (58.1%) developed infection during the first 120 hours after admis-
Amyloid angiopathy 8 (12.9%) sion. Thirty-one (50%) patients had pneumonia, 2 had urinary
Arteriovenous malformation 8 (12.9%) infections (3.2%), and 4 (6.4%) had clinical and laboratory
Coagulopathy (including OAT) 5 (8%) signs of infection with no evident focus. There was no
Other defined 1 (1.6%) statistical difference in any of the clinical or neuroradiologi-
cal variables between patients with pneumonia, urinary infec-
Unknown 4 (6.5%)
tion, or clinical laboratory signs of infection with no evident
NIHSS score at admission, median (range; IQR) 13.5 (1–34; 29)
focus. However, this also may be attributable to the low
Hemorrhage volume (mL), median (range; IQR) 28.6 (0.3–234; 52.4) frequencies in the infection subgroups other than pneumonia.
Localization All 36 patients with infection received antibiotic treatment.
Lobar 25 (40.3%) Univariate analysis of variables associated with infection is
Deep 34 (54.9%) shown in Table 2. We further performed a stepwise multi-
Pons 2 (3.2%) variate logistic regression model including the variables BRS,
Cerebellar 1 (1.6%) NIHSS score at admission, lesion volume, LeRoux intraven-
tricular hemorrhage score, aspiration, and invasiveness score
IVH extension 31 (50%)
to predict infections. BRS (OR, 0.54; 95% CI, 0.32– 0.91;
LeRoux IVH score, mean (range; SD) 4.6 (0–16; 5.8)
P⫽0.02) and invasiveness score (OR, 2.32; 95% CI, 1.5–3.6;
History of hypertension 47 (75.8%) P⬍0.001) remained the only independent predictors for an
Previous antihypertensive therapy 20 (32.2%) early infection after ICH (Table 3). This model predicted
␤-blockers 9 (14.5%) 88.5% of all infections. Admission NIHSS score, hema-
Angiotensin-converting enzyme 20 (32.2%) toma volume, and intraventricular hemorrhage extension
inhibitors/angiotensin-receptor antagonists by LeRoux score correlated strongly with the invasiveness
Calcium channel antagonists 8 (12.9%) score (r⫽0.8 for NIHSS score at admission; r⫽0.7 for
Diuretics 4 (6.4%) hematoma volume; r⫽0.7 for LeRoux intraventricular hem-
ICH indicates intracerebral hemorrhage; IQR, interquartile range; IVH,
orrhage score; all P⬍0.001). Thus, removal of the invasive-
intraventricular hemorrhage; NIHSS, National Institute of Health Stroke Scale; ness score from the model resulted in significance of the
OAT, oral anticoagulant treatment. predictors BRS (OR, 0.64; 95% CI, 0.42– 0.97; P⫽0.03),
admission NIHSS score (OR, 1.1; 95% CI, 1.02–1.23;
analysis was used to select which of the variables should be included P⫽0.02), and LeRoux score (OR, 1.3; 95% CI, 1.01–1.6;
in a regression model to predict the dependent variable. The P⫽0.04), with unchanged model fit predicting 88.5% of
procedure applied the variables 1 by 1 using a criterion such that the infections. Because of multicollinearity effects, aspiration did
F statistic for the variable to be added must exceed the level of 0.05.
After a variable was added to the model, the procedure analyzes all
not remain an independent predictor of infection. Aspiration
included variables and deletes any variable that fails to produce an F correlated with hemorrhage volume (r⫽0.26; P⫽0.04), with
value ⬍0.1. After necessary deletions are accomplished, a further admission NIHSS score (r⫽0.34; P⫽0.005), with LeRoux
variable can be added to the model. The procedure terminates when intraventricular hemorrhage score (r⫽0.42; P⫽0.001), and
no variable outside the model exceeds the necessary threshold and with invasiveness score (r⫽0.42; P⫽0.001).
every variable included is significant. Values of P⬍0.05 were
considered statistically significant in all tests. All statistics were BRS correlated with intraventricular hemorrhage extension
performed using statistical software SPSS 16.0 for Windows. as quantified by LeRoux score (P⫽⫺0.38; P⫽0.003). BRS
did not correlate with NIHSS score at admission or hemor-
Results rhage volume. Using a partial regression, we explored the
Sixty-two patients with acute ICH met the inclusion criteria relationship between BRS and intraventricular hemorrhage
and entered the analysis. The demographic, clinical, and extension. LeRoux intraventricular hemorrhage score corre-
neuroradiological characteristics of the patient population are lated with BRS independently of NIHSS score at admission
shown in Table 1. Median BRS at admission was 2.7 and lesion volume (adjusted r⫽⫺0.38; P⫽0.003).
ms/mm Hg (range, 0.7–21.1; IQR, 3.2). Age, history of
hypertension, and previous antihypertensive treatment includ- Discussion
ing urapidil use on admission showed no influence on the Experimental and clinical evidence suggests that temporary
measured BRS values. Thirty-three (53.2%) patients were immunodeficiency in acute stroke is mediated by enhanced
treated in the ICU; of those, 31 (50%) required mechanical sympathetic activation. Several studies found a strong asso-
ventilation. All patients treated in the ICU received urinary ciation between high catecholamine levels and poststroke
catheters, central venous catheters, and nasogastric tubes. infections in patients with acute ischemic stroke.7,25 However,
External ventricular drain placement was performed in 26 data for patients with ICH are missing. Most recently,
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 Sykora et al Automic Shift and Infections After ICH 1221

Table 2. Univariate Analysis of Variables Associated With Infections After ICH

Variable No Infection (n⫽26) Infection (n⫽36) P
BRS (ms/mm Hg), median (range; IQR) 4.1 (1.2–21.1; 6.4) 2.2 (0.7–7.7; 1.5) 0.002†
Age (years), mean (range; SD) 62.8 (17–82; 18.3) 60.5 (34–86; 14) NS‡
History of hypertension 20 (76.9%) 27 (75%) NS*
NIHSS score at admission, median (range; IQR) 5 (1–34; 9) 20 (5–34; 21.7) ⬍0.001†
Lesion volume (mL), median (range; IQR) 9.9 (0.3–234; 15.1) 49 (2.2–225; 65.6) ⬍0.001†
IVH 5 (19.2%) 26 (72.2%) ⬍0.001*
LeRoux IVH score, mean (range; SD) 0.16 (0–10; 2) 7.6 (0–16; 5.8) ⬍0.001†
Aspiration 0 16 (44.4%) ⬍0.001*
Invasiveness score, median (range; IQR) 0 (0–7; 2) 6 (0–7; 1) ⬍0.001†
ICU stay 5 (19.2%) 28 (77.8%) ⬍0.001*
Mechanical ventilation 3 (11.5%) 28 (77.8%) ⬍0.001*
EVD placement 1 (3.8%) 25 (69.4%) ⬍0.001*
Hematoma evacuation 1 (3.8%) 15 (41.4%) ⬍0.001*
Central venous catheter 5 (19.2%) 29 (80.6%) ⬍0.001*
Urinary catheter 12 (46.2%) 35 (97.2%) ⬍0.001*
Nasogastric tube 4 (15.4%) 31 (86.1%) ⬍0.001*
BRS indicates baroreflex sensitivity; EVD, external ventricular drainage; ICH, intracerebral hemorrhage; ICU,
intensive care unit; IQR, interquartile range; IVH, intraventricular hemorrhage; NIHSS, National Institute of Health
Stroke Scale; NS, not significant.
*Fisher exact test.
†Mann–Whitney U test.
‡Student t test.

neutrophil respiratory burst has been found to be suppressed
in patients with hemorrhagic stroke, correlating strongly with
plasma noradrenalin concentration.9 In agreement with pre-
vious studies in ischemic stroke, we found decreased BRS
mirroring autonomic shift toward sympathetic predominance
to be independently linked to higher occurrence of infection
after ICH. The relationship between autonomic shift and
immunodepression seems plausible. The extensive sympa-
thetic innervations of immune organs and the presence of
adreneregic receptors on almost all types of leukocytes
indicate that immune functions are strongly determined by
the level of sympathetic activity.5 Experimental data show
that prolonged exposure to catecholamines results in lympho-
cyte depletion, reduced NK-cell activity, decreased produc-
tion of interferon-␥, IL-2 by Th1 helpers, and tumor necrosis
factor-␣, and IL-1␤ and IL-12 from monocytes.5,6 This
phenomenon seems to be present through the whole spectrum
Table 3. Final Stepwise Multivariate Logistic Regression
Model Predicting Infections After ICH
OR 95% CI
BRS (per ms/mm Hg) 0.54 0.32– 0.91
Admission NIHSS (per point) … …
Hemorrhage volume (per mL) … …
LeRoux IVH score (per point) … …
Aspiration (present/absent) … …
Invasiveness score (per point) 2.32 1.5–3.6
BRS indicates baroreflex sensitivity; CI, confidence interval; ICH, intracere-
bral hemorrhage; IVH, intraventricular hemorrhage; NIHSS, National Institute of
Health Stroke Scale; NS, not significant at P⬎0.05; OR, odds ratio.
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of acute nervous system injuries, including ischemic stroke,
traumatic brain injury, subarachnoid hemorrhage, or spinal
cord injury.26
Interestingly, we found that autonomic shift is associated
with higher frequency of infections independently of stroke
severity or intracerebral blood volume. This finding is con-
sistent with a previous study showing a relationship between
catecholamines and poststroke infections that was indepen-
dent of stroke severity.10 Interestingly, some small studies
found a localization-dependent pattern in immune dysfunc-
tion after stroke.27,28 However, others did not confirm this
finding.29 More importantly, previous studies investigated
patients with ischemic stroke. In intracerebral hemorrhage,
however, other factors such as intraventricular blood in the
vicinity of autonomic and immunoregulatory centers (thala-
mus, hypothalamus, peri-aqueductal gray, formatio reticu-
laris) may play a key role in sympathetic activation and, thus,
in subsequent immunodepression. We found a strong rela-
tionship between intraventricular hemorrhage extension and
sympathetic activation that was independent of hemorrhage
volume and initial stroke severity.
P
Unlike in previous studies, there was no correlation be-
0.02
tween BRS and age or history of hypertension in our series.
NS However, these associations originate from studies with
NS nonstroke patients with a larger number of subjects.30,31 Thus,
NS we assume that our cohort most likely was too small to show
NS a correlation between BRS and age or hypertension, and that
⬍0.001 these effects, if present, presumably were overruled by the
more profound baroreflex impairment related to stroke.14
Certain limitations of our study have to be acknowledged.
First, it is the retrospective character of our study. The
1222 Stroke May 2011
retrospective identification and classification of infections
have led to the fact that not all information required by
standard scores, such as the Centers for Disease Control
definitions of health care-associated infections, could be
obtained.22 For example, the Centers for Disease Control
criteria for urinary tract infection— dysuria, urgency, and
frequency— cannot be assessed in sedated and ventilated
patients or in patients with urinary catheters. Additionally,
our protocol allowed classification of infections without
microbiological confirmation. This may overestimate the
occurrence of infections, because patients with probable or
only possible infection according to current guidelines were
included.21 However, it is a common difficulty in clinical
studies that microbiological work-up frequently yields no
specific result, possibly because of the early empirical anti-
biotic treatment for suspected infection, especially in ICU
patients. Thus, it has been suggested previously that standard
definitions may not be appropriate for ICU patients.21 Sec-
ond, CRP elevation, leukocytosis, and fever may occur after
stroke independently of infection, rendering a potential bias
for accurate identification of infections. Therefore, we cannot
completely exclude other mechanisms that may be responsi-
ble for the laboratory and clinical findings suggestive for an
infection. This in particular holds true for the subgroup of
patients without clearly identified infectious focus (group 3).
However, 86.1% of the infected patients in our cohort had
pneumonia, defined by a positive chest radiograph, and
another 5.5% had positive urine findings. Third, because of
the criteria for nonbiased BRS estimation, we excluded
patients with previous stroke, myocardial infarction, atrial
fibrillation, diabetes mellitus, or other conditions known to
affect autonomic functions, as well as patients with actual
antihypertensive treatment, thus producing a selection bias.
This bias possibly limits the translation of our results into the
general ICH population.
With accumulating evidence that sympathetic activation
plays a central role in the immunodepression associated with
central nervous system injury, the question of therapeutic
targeting arises. Until now, studies investigating prophylactic
antibiotic treatment after acute stroke rendered inconclusive
results.32,33 Data on adrenergic blockade possibly ameliorat-
ing the consequences of sympathetic activation after stroke
are scarce. In animals, the occurrence of bacterial infections after
stroke can be prevented by administration of ␤-blockers.6 Inter-
estingly, in a retrospective study, stroke patients with ␤-blocker
treatment less often had pneumonia develop after stroke.34 Thus,
hypothetically, the modulation of autonomic nervous system
function, alone or in combination with prophylactic antibiotic
treatment, may represent an attractive therapeutic option in
preventing (not only) infective complications after stroke. Of
clinical interest is that BRS may be used as a reliable marker
for increased susceptibility to infections after acute stroke and
may help to select patients suitable for intensive anti-infective
prevention.
Conclusions
Decreased BRS was independently associated with infections
after ICH. Autonomic shift may play an important role in
increased susceptibility to infections after acute brain injury
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including ICH. The pathophysiology of ICH, however, may
differ from ischemic stroke and other insults. In our study,
autonomic shift in ICH was independently linked to intraven-
tricular hemorrhage extension. The future therapeutic modu-
lation of autonomic functions warrants further studies.
Sources of Funding
This study has been partially conducted within the realization of the
project “Centre of Excellence for Strokes at the Faculty of Medicine,
Comenius University, Bratislava, Slovakia” and supported by the
operation programme of research and development financed by the
European Reconstruction and Development Fund.
Disclosures
None.
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 Autonomic Shift and Increased Susceptibility to Infections After Acute Intracerebral
Hemorrhage
Marek Sykora, Jennifer Diedler, Sven Poli, Timolaos Rizos, Peter Turcani, Roland Veltkamp
and Thorsten Steiner

Stroke. 2011;42:1218-1223; originally published online March 10, 2011;

doi: 10.1161/STROKEAHA.110.604637
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