Beasley, Anne W. Alexandrov, Andrei V. Alexandrov and David W. Miller
Reza Bavarsad Shahripour, Muhammad Alvi, J. Thomas Houston, April Sisson, T. Mark
Amelia K. Boehme, Niren Kapoor, Karen C. Albright, Michael J. Lyerly, Pawan V. Rawal,
Treated Patients is Associated With Worse Short-term Functional Outcome
Systemic Inflammatory Response Syndrome in Tissue-Type Plasminogen Activator
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surgery) characterized by the absence of infection and the pres-
ence of ≥2 of the following: body temperature changes (<36°C
or >38°C), leukocytosis or leukopenia, elevated heart rate or
elevated respiratory rate.1 Stroke itself can produce an inflam-
matory response, with inflammation playing a role in the patho-
physiology of tissue damage through ischemia–reperfusion
injury.2–5 Previous research has shown that patients with acute
ischemic stroke with more severe strokes are at higher odds of
having SIRS, but successful thrombolytic therapy with intrave-
nous tissue-type plasminogen activator (tPA) has been shown
to attenuate this process.6 We investigated the differences in
outcomes in tPA-treated patients with SIRS and without SIRS.
ystemic inflammatory response syndrome (SIRS) is a gen-
eralized whole body reaction to a stimulus (ie, trauma and
Study Population and Variable Definition
We retrospectively identified consecutive tPA-treated patients
who presented to our center from 2008 to 2011 using our stroke
registry. Patients who developed SIRS during their hospital stay
were identified via chart review. SIRS was defined as the presence
of ≥2 of the following: (1) body temperature <36°C or >38°C,
(2) heart rate >90, (3) respiratory rate >20, or (4) white blood
cells <4000/mm or >12 000/mm or >10% bands for >24 hours.
The focus of our study was SIRS, not sepsis or other detected in-
fection; thus, patients who were diagnosed with an infection were
Three outcomes were examined. Poor functional outcome, defined
as a modified Rankin Scale of 4 to 6 at discharge, poor discharge
disposition (being discharged somewhere other than home or an
inpatient rehabilitation center), and death.
Patients with SIRS were compared with those without SIRS using χ2
and t tests with nonparametric equivalents when appropriate. Logistic
regression analyses were conducted to assess the relationship be-
tween SIRS and outcomes of interest. As this was an exploratory
analysis, no adjustments were made for multiple comparisons. An
α of 0.05 was set as the level of significance. This study was ap-
proved by the institutional review board at the University of Alabama
Background and Purpose—Systemic inflammatory response syndrome (SIRS) is a generalized inflammatory state. The
primary goal of the study was to determine whether differences exist in outcomes in SIRS and non-SIRS intravenous
tissue-type plasminogen activator–treated patients.
Methods—Consecutive patients were retrospectively reviewed for the evidence of SIRS during their admission. SIRS was defined
as the presence of ≥2 of the following: body temperature <36°C or >38°C, heart rate >90, respiratory rate >20, and white
blood cells <4000/mm or >12 000 mm, or >10% bands. Patients diagnosed with infection (via positive culture) were excluded.
Results—Of the 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre–tissue-type plasminogen activator National
Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge (odds
ratio [OR], 2.58; 95% confidence interval [CI], 1.16–5.73; P=0.0197).
Conclusions—In our sample of tissue-type plasminogen activator–treated (tPA) patients, ~1 in 5 patients developed SIRS.
Furthermore, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged
length of stay. (Stroke. 2013;44:2321-2323.)
Key Words: inflammation ◼ ischemic stroke ◼ stroke care ◼ tPA
Systemic Inflammatory Response Syndrome in Tissue-Type
Plasminogen Activator–Treated Patients is Associated With
Worse Short-term Functional Outcome
Amelia K. Boehme, MSPH*; Niren Kapoor, MD, PhD*; Karen C. Albright, DO, MPH;
Michael J. Lyerly, MD; Pawan V. Rawal, MD MHA; Reza Bavarsad Shahripour, MD; Muhammad Alvi, MD;
J. Thomas Houston, MD; April Sisson, RN; T. Mark Beasley, PhD; Anne W. Alexandrov, PhD;
Andrei V. Alexandrov, MD; David W. Miller, MD
Received March 14, 2013; accepted March 21, 2013.
From the Stroke Center, Department of Neurology..... (A.K.B., N.K., K.C.A., M.J.L., P.V.R., R.B.S., M.A., J.T.H., A.S., A.W.A., A.V.A.), Department
of Epidemiology (A.K.B., K.C.A.), Health Services and Outcomes Research Center for Outcome and Effectiveness Research and Education (COERE;
K.C.A.), Center of Excellence in Comparative Effectiveness Research for Eliminating Disparities (CERED) and Minority Health & Health Disparities
Research Center (MHRC; K.C.A), Department of Biostatistics (T.M.B.), School of Nursing (A.W.A.), and Department of Anesthesiology, School of
Medicine (D.W.M.), University of Alabama at Birmingham, Birmingham, AL.
*Drs Boehme and Kapoor contributed equally to this article.
Corresponding to David W. Miller, MD, Department of Anesthesiology, School of Medicine, Jefferson Tower 922, Birmingham, AL 35294-6810. E-mail
© 2013 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.113.001371
2322 Stroke August 2013
Of the 241 tPA-treated patients included in this study, 44 had
evidence of SIRS (18.2%). The Table demonstrates the differ-
ences in baseline characteristics between patients with SIRS
and patients without SIRS. Patients with SIRS were more likely
to be black (48 versus 25%; P=0.0117) and had lower median
total cholesterol at baseline (143 versus 168 mg/dL; P=0.0207).
Patients with SIRS were more likely to have a longer length
of stay than those without SIRS (5 versus 3 days; P<0.0001).
Although patients with SIRS had higher odds of poor functional
outcome at discharge (OR, 2.82; 95% CI, 1.36–5.87; P=0.0054),
there was no association between SIRS and discharge disposition
(OR, 1.26; 95% CI, 0.56–2.80; P=0.5770) or death (OR, 1.98;
95% CI, 0.77–5.06; P=0.1545). Even after adjusting for National
Institutes of Health Stroke Scale on admission, age, black race,
and evidence of prior stroke, SIRS remained predictive of poor
functional outcome (OR, 3.55; 95% CI, 1.47–8.58; P=0.0049).
Our study showed that ≈1 in 5 of our tPA-treated patients
developed SIRS. Given that prior studies have shown that
Table. Baseline and Outcome Characteristics
No SIRS (n=197)SIRS (n=44)P Value
Age, y median (range)
Sex, % male
Black, n (%)
Medical history, n (%)
On BP medications at home, n (%)
On DM medications at home, n (%)
On AP medications at home, n (%)
Transfer, n (%)
NIHSS on admission, median (range)
LOS, median (range)
Glucose, median (range)
Total cholesterol, median (range)
Transfusion, n (%)
Follow-up imaging, n (%)
Hemorrhagic transformation, n (%)
SIRS criteria, n (%)
On nicardipine, n (%)
mRS on admission, median (range)
mRS on discharge, median (range)
Favorable discharge disposition*, n (%)
mRS 0–2, n (%)
Death, n (%)21 (10.7)8 (18.2) 0.1656
AP indicates antiplatelet; BP, blood pressure; DM, Diabetes; ESRD/CKD, End Stage Renal Disease/Chronic Kidney Disease; HF, Heart Failure; HR, heart rate; LOS,
Length of Stay; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; RR, respiratory rate; SIRS, systemic inflammatory response syndrome;
and WBC, white blood cells.
*Favorable discharge disposition was defined as discharge home or to inpatient rehabilitation.
Boehme et al SIRS in AIS 2323 Download full-text
successful tPA therapy diminishes the risk of adverse outcomes
associated with SIRS,6 we sought to assess the differences in
outcomes in patients with SIRS treated with tPA. Patients who
developed SIRS were at greater odds of being discharged with
poor functional outcomes, even after adjusting for covariates
previously shown to influence outcome. Yoshimoto et al7 dem-
onstrated that SIRS was associated with clinical worsening
and poor outcomes after subarachnoid hemorrhage. Despite
the increased odds of poor functional outcome, SIRS was not
a predictor of poor discharge disposition or in-hospital mor-
tality in our sample. Although infection after stroke remains
a significant predictor of poor outcome, there has been little
research on SIRS in the absence of infection as a predictor
of outcome.8–11 Because individual components of the SIRS
classification were linked to poor outcomes (eg, leukocytosis,
elevated body temperature), it is plausible that the combined
effects of the components within SIRS are related to poor out-
comes, despite attenuation from thrombolytic therapy.6,12,13
Our study is limited by a small sample size involving only
1 academic center, which may limit its generalizability. We
are further limited by the retrospective nature of this study.
Although our outcomes were not blinded, all data on SIRS cri-
teria were collected separately from the stroke outcome data.
We examined only short-term outcomes because long-term
data were not available. Furthermore, levels of inflammatory
markers such as high-sensitivity C-reactive protein or vari-
ous interleukins were not available. Prospective studies that
include the measurement of inflammatory markers to deter-
mine whether there is an elevated inflammatory response in
patients who develop SIRS and to determine whether levels
correlate with clinical outcome are needed.
Despite its influence on functional outcome and its prevalence,
SIRS is often overlooked in the ischemic stroke population.
Larger prospective studies are needed to determine whether
early identification of patients at risk of SIRS could serve to
mitigate the risk of poor functional outcome in this vulnerable
Dr Albright is supported by Award numbers 5 T32 HS013852-10
from the Agency for Healthcare Research and Quality (AHRQ) and
3 P60 MD000502-08S1 for the National Institute on Minority Health
and Health Disparities (NIMHD) and National Institutes of Health
(NIH). A.K. Boehme is supported by award 13PRE13830003 from
the American Heart Association (AHA). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the AHRQ, AHA or the NIH.
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