ARTICLE IN PRESS

Risk Factors and Stroke Characteristic in Patients with

Postoperative Strokes

Yi Dong, MD,*,† Wenjie Cao, MD , PhD,*,† Xin Cheng, MD, PhD,*,† Kun Fang, MD ,*,†
Xiaolong Zhang, MD, PhD,‡ Yuxiang Gu, MD, PhD,§ Bing Leng, MD , PhD,§ and
Qiang Dong, MD, PhD*,†

Background: Intravenous thrombolysis and intra-arterial thrombectomy are now the

standard therapies for patients with acute ischemic stroke. In-house strokes have
often been overlooked even at stroke centers and there is no consensus on how they
should be managed. Perioperative stroke happens rather frequently but treatment
protocol is lacking, In China, the issue of in-house strokes has not been explored.
The aim of this study is to explore the current management of in-house stroke and
identify the common risk factors associated with perioperative strokes. Method: Al-
together, 51,841 patients were admitted to a tertiary hospital in Shanghai and the
records of those who had a neurological consult for stroke were reviewed. Their
demographics, clinical characteristics, in-hospital complications and operations, and
management plans were prospectively studied. Routine laboratory test results and
risk factors of these patients were analyzed by multiple logistic regression model.
Result: From January 1, 2015, to December 31, 2015, over 1800 patients had neu-
rological consultations. Among these patients, 37 had an in-house stroke and 20 had
more severe stroke during the postoperative period. Compared to in-house stroke
patients without a procedure or operation, leukocytosis and elevated fasting glucose
levels were more common in perioperative strokes. In multiple logistic regression
model, perioperative strokes were more likely related to large vessel occlusion.
Conclusion: Patients with perioperative strokes had different risk factors and se-
verity from other in-house strokes. For these patients, obtaining a neurological consultation
prior to surgery may be appropriate in order to evaluate the risk of perioperative
stroke. Key Word: Risk factor—perioperative—stroke—in-house stroke.
© 2017 Published by Elsevier Inc. on behalf of National Stroke Association.

From the *Department of Neurology, Fudan University, Huashan

Hospital, Shanghai, China; †State Key Laboratory of Neurobiology,
Fudan University, Shanghai, China; ‡Department of Radiology, Fudan
University, Huashan Hospital, Shanghai, China; and §Department
of Neurosurgery, Fudan University, Huashan Hospital, Shanghai, China.
Received October 14, 2016; revision received November 29, 2016;
accepted December 23, 2016.
Funding: Q.D. is funded by the National Nature Science of China
(81571109). X.C. is funded by the National Nature Science of China
(81100861) and sponsored by the Shanghai Rising-Star Program from
Science and Technology Commission of Shanghai Municipality
(15QA1400900).
Address correspondence to Qiang Dong, MD, Department of Neu-
rology, Fudan University, Huashan Hospital, No. 12 Wulumuqi Middle
Road, Shanghai 200040, China. E-mail: qiang_dong163@163.com
1052-3057/$ - see front matter
© 2017 Published by Elsevier Inc. on behalf of National Stroke
Association.
ttp://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.12.017
Introduction
Several international thrombolysis registries have re-
ported that between 6.5% and 15% of all strokes occur
in patients who were hospitalized.1 Many of them were
admitted for surgical operations or cardiac diseases. Certain
operations were also associated with strokes. For example,
6% of strokes were related to carotid endarterectomy (CEA)
or carotid angioplasty or stenting (CAS) when treating
symptomatic carotid diseases, 2% from asymptomatic CEA
or CAS, 2 3% during coronary artery bypass graft,3 6%
during cardiac valve replacement, 5% during cerebral an-
eurysm clipping or coiling, and 10% from descending
thoracic aortic repair.4 However, stroke risks associated
with medical conditions or other stress factors during hos-
pitalization have rarely been reported. One study found

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■ 1
 ARTICLE IN PRESS
2 Y. DONG ET AL.
that 3.5% of in-hospital strokes were related to surgical
operations.5 Another study reported that 15% of in-
house strokes were related to cancers.6 The number of
strokes reported could still be underestimated because
of observational bias. For example, minor strokes were
difficult to identify in hospitalized patients. Therefore, in-
house stroke may be common but underestimated and
rarely reported.
Furthermore, 1 major challenge of treating in-house
stroke was the delay of recognition and assessment.
These patients often had different comorbidities such as
postoperation state (e.g., cardiac surgery), fever, dehy-
dration, and previous medical disorders (especially
history of stroke, carotid artery occlusion). They often had
poor outcome and a high mortality. Treatment options
were limited because of recent operations or other
contraindications.
In China, there are 2.5 million new stroke patients each
year and stroke is the leading cause of mortality. However,
it has not been explored how in-house stroke and its as-
sociated risk factors are managed. Currently, there are no
standardized ways to manage in-house strokes, especial-
ly for those with perioperative strokes. Therefore, we aim
to examine the real-world in-house stroke at a compre-
hensive stroke center of a tertiary care hospital in Shanghai
in order to elucidate how they are identified, triaged,
and treated. In addition, any common risk factors asso-
ciated with perioperative strokes would be studied and
analyzed.
Materials and Methods
Subjects
This was a retrospective study approved by the Insti-
tutional Review Board (IRB) of Huashan Hospital. Records
of all patients diagnosed with stroke or intracerebral hem-
orrhage (ICH) were reviewed. From January to December
2015, Huashan Hospital admitted 51,841 patients. Only
patients with a diagnosis of ICH or ischemic stroke were
included in this analysis. Their demographics, clinical char-
acteristics, in-hospital complications and operations, and
management plans were studied. We stratified the gender,
comorbidity, and stroke subtypes. The study was granted
the waiver from Huashan Hospital IRB based on that we
only use deidentified health information in our registry
system, which causes no more than minimal risk to the
privacy of individuals.
Enrollment
In-house stroke was defined as new symptoms that oc-
curred when patient was in the hospital and a magnetic
resonance imaging scan of brain showed lesions of acute
stroke on the diffusion-weighted sequence. All in-house
stroke patients at least had a brain computed tomography
(CT) scan and a set of blood tests as those of community
stroke patients. At Huashan Hospital, the protocol states
that to assess and treat in-house stroke is the responsi-
bility of the consultant neurologist 24 hours 7 days a week.
A possible in-house stroke patient could be seen within
10 minutes after being called. The consultant neurologist
would assess, diagnose, and treat in-house stroke first
and then refer the patient to the stroke team quickly.
The stroke team would assume the care if the stroke is
severe and the patient is of high risk. Only those with
confirmed diagnosis of acute intracranial hemorrhage or
ischemic stroke by a stroke doctor were included in this
analysis. Other rare vascular diseases such as cerebral venous
sinus thrombus, arteriovenous malformation, and arte-
riovenous fistula were excluded. We also excluded patients
with neurological defects from a previous stroke.
Outcome Measurements
All demographics, clinical characteristics, in-hospital com-
plications and any related operations, and subsequent
management plan were recorded and compared to those
with strokes coming through the emergency room (ER).
Based on the risk factors, these patients were stratified
into these categories: postoperative, under stressful con-
dition with or without infection, cancer, and hypercoagulable
state. Perioperative stroke was defined as a patient who
had a stroke during operation duration or post opera-
tion. Stressful condition was defined as sudden onset of
any disorder not caused by infection, cancer, operations,
or vascular events. These conditions included trauma, bone
fracture, intestinal obstruction, and so on.
The primary outcome is to explore the current status
and management of in-house stroke. Furthermore, we
would identify the common risk factors associated with
perioperative strokes, compared to nonperioperative
strokes.
Statistical Analysis
All variables were compared between in-house stroke
patients with or without an operation. Analysis of vari-
ance test was used for continuous variables and Fisher
exact test for categorical variables. All risk factors (P = .10
as the criterion) were entered into multiple logistic re-
gression analysis to explore the predictor of in-house stroke.
Age as an independent risk factor was also included.
Bivariable logistic regression was used to analyze the dif-
ference between postoperative and other strokes. SPSS
22.0 (International Business Machines Corporation, New
York, USA) was used to perform logistic regression analysis.
Results
During the 12 months, consultant neurologists evalu-
ated over 1800 patients. Among them, the diagnosis of
37 in-house strokes (male 20 cases, female 17 cases) was
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PERIOPERATIVE STROKE 3
Table 1. Characteristics of patients with perioperative strokes

Stroke
No. Gender Age Operations Primary disease type Primary symptom

1 M 75 Carotid artery Carotid stenosis IS Left facial droop and aphasia

endarterectomy
2 M 72 Colon cancer colectomy Colon cancer IS Bilateral upper and lower
limbs weakness
3 F 65 Gastrectomy Gastric cancer IS Hemiparesis
4 M 78 Ureteroscopy Kidney abscess, myocardial IS Right paralysis
infarction
5 M 81 DSA Iliac artery stenosis IS Unconsciousness
6 M 60 Lung biopsy Lung cancer IS Facial droop and right arm
weakness, hemianopia,
ataxia, aphasia, cannot
follow commands
7 M 52 DSA Aneurysm, CCF IS Seizure
8 F 83 Hematoma removal Post hip joint replacement IS Right arm weakness
9 F 75 PCI and drug-eluting stent Ischemic coronary disease IS Left facial droop and left arm
implantation weakness
10 F 59 Post-op 7 d Meningioma surgery IS Left paralysis
11 M 52 Liver resection Liver cancer IS Left paralysis and
unconsciousness
12 M 67 Began DSA Intracranial artery stenosis IS Unconsciousness
13 F 81 Hip joint replacement Hip joint fracture IS Unconsciousness, right lower
limb weakness, secondary
seizure
14 F 24 Pituitary surgery Pituitary tumor IS Left paralysis
15 M 81 Cardiac pacemaker Myasthenia gravis IS Unconsciousness
implantation
16 M 61 Heart valve replacement Rheumatic mitral stenosis IS Unconsciousness and aphasia
17 F 77 Rectal cancer colectomy Rectal cancer IS Left paralysis
18 M 65 Kidney biopsy ANCA vasculitis, fungi IS Seizure
infection
19 M 74 CEA Bilateral carotid artery IS Left paralysis
stenosis
20 F 60 ERCP Pancreatic cancer IS Left side weakness

Abbreviations: ANCA, anti-neutrophil cytoplasmic auto-antibody; CCF, carotid cavernous fistula; CEA, carotid artery endarterectomy; DSA,
digital subtraction angiography; ERCP, endoscopic retrograde cholangiopancreatography; IS, ischemic stroke; PCI, percutaneous coronary
intervention.

confirmed by stroke doctors. Four of the patients had in-
tracranial hemorrhage and 33 had an ischemic stroke. The
average age was 67.3  12.3 years and the average base-
line National Institutes of Health Stroke Scale score was
7.0  8.0. The clinical history of patients with perioperative
strokes was listed in Table 1. Patients with in-house strokes
not related to operations were compared to patients with
perioperative strokes on their medical history and clin-
ical characteristics (Table 2). The time of onset was unclear
in patients with perioperative strokes. Compared to pa-
tients without an operation, these stroke patients commonly
had elevated levels of fasting glucose and leukocytosis.
One third of in-house stroke patients had large vessel
occlusions with massive infarctions. Most of these in-
farctions occurred in the anterior circulation. Six of 33
patients had multiple stroke lesions in more than 1 vascular
territory, which were likely due to embolism. Two thirds
had at least 2 stroke risk factors (Table 3).
By using logistic regression analysis, patients with
perioperative stroke had more large vessel occlusion
(HR 4.825, 95% CI 1.061-21.948, P = .042). Infection with
leukocytosis showed no statistical difference between
perioperative stroke and other in-house stroke (HR 1.013,
95% CI .048-1.376, P = .112).
When considering treatment options, individualized
therapies were likely implemented rather than standard-
ized protocols because these patients had many
contraindications such as preoperation status, active cancer
state, and life expectancy of less than 2 years. However,
most patients who developed perioperative strokes still
 ARTICLE IN PRESS
4 Y. DONG ET AL.
Table 2. Comparison of baseline characteristics between patients with or without postoperative infarctions

Nonoperation Perioperation Total

N  17 N  20 N  37

Average, SD Average, SD Average, SD P

Age (y) 66.8 (10.7) 67.1 (14.1) 67.0 (12.5) .95

Gender (F) 9 (52.9%) 8 (40%) 17 (45.9%) .43
Gender (M) 8 (47.1%) 12 (60%) 20 (54.1%)
Department .01
Surgical department 2 (11.8%) 15 (75%) 17 (45.9%)
Medicine department 15 (88.2%) 5 (25%) 20 (54.1%)
Clinical manifestation
Limb weakness/numbness 10 (50%) 10 (50%) 20 (54.1%) .77
Facial droop 4 (23.5%) 7 (35%) 11 (29.7%) .48
Speech problem 1 (5.9%) 4 (20%) 5 (13.5%) .30
Consciousness 5 (29.4%) 8 (40%) 13 (35.1%) .51
Baseline NIHSS 5.1 (7.2) 9.5 (8.7) 7.0 (8.0) .06
Clinical quality measurement
Onset time unknown 5 (29.4%) 12 (60%) 17 (45.9%) .10
Onset to CT (min) 190 (292) 293 (181) 227 (255) .49
Onset to neurologist (min) 185 (304) 513 (221) 267 (313) .12
Result of laboratory test
Leukocytosis 5 (29.4%) 8 (40%) 13 (35.1%) .04*
Coagulopathy 15 (88.2%) 16 (80%) 31 (83.8%) .21
Elevated fasting glucose 4(23.5%) 7 (35.0%) 11 (29.7%) .004*

Abbreviations: CT, computed tomography; NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation.
Note: Median onset to neurologist was 19 minutes in 4 patients; however, median of onset to thrombectomy was 180 minutes.
*Those variables in patient with perioperative stroke has statistically difference from those in patients with nonperioperative stroke.

Table 3. Imaging and risk factor analysis of all strokes

Without operation Perioperation Total

N  17 N  20 N  37 P value

Site of infarction .03

Anterior circulation 8 (47.1%) 14 (70%) 24 (64.7%)
Posterior circulation 3 (17.6%) 0 (0%) 3 (8.1%)
Both anterior and posterior involved or bilateral involved 5 (29.4%) 1 (5%) 6 (16.2%)
Location of vessel occlusion .15
ICA 0 (0%) 4 (20%) 4 (10.8%)
ACA or MCA 5 (29.4%) 16 (80%) 21 (56.9%)
VA-BA 2 (11.8%) 0 (0%) 2 (5.4%)
Feature of lesions
Massive 11(64.7%) 2 (10%) 13 (35.1%) .16
Combination of other risk factor
Cancer/hypercoagulable state 7 (41.2%) 7 (35%) 14 (37.8%) .70
Infection 7 (41.2%) 3 (15%) 10 (27.0%) .07
Stress 3 (17.6%) 3 (15%) 6 (16.2%) .69
High vascular risk 2 (11.8%) 3 (15%) 5 (13.5%) .83
Number of risk factors .77
None or one other risk factor 15 (88.2%) 17 (85%) 32 (86.5%)
Two other risk factors or more 2 (11.8%) 3 (15%) 5 (13.5%)

Abbreviations: ACA, anterior cerebral artery; BA, basilar artery; ICA, internal carotid artery; MCA, middle cerebral artery; PCA, poste-
rior carotid artery; VA, vertebral artery.
High vascular risk includes 1 of the following: severe large vessel occlusion or stenosis of 70%, atrial fibrillation, mechanical valve re-
placement, and coronary artery bypass grafting; or 3 of the following: hypertension, diabetes, obesity, coronary artery disease, age, and dyslipidemia.
 ARTICLE IN PRESS
PERIOPERATIVE STROKE
received intravenous (IV) thrombolysis, intra-arterial (IA)
thrombolysis, and thrombectomy (Supplemental Table S1).
Among them, 1 patient with symptomatic carotid artery
stenosis who suffered from a severe stroke on the third
day post C E A was given IV tissue plasminogen activa-
tor within 4 hours. Three patients with middle cerebral
artery occlusive strokes during perioperation period
were given IA thrombectomy within 6 hours and fully
recovered. One patient with Steven Johnson syndrome
developed the top of basilar artery syndrome. He re-
ceived IA stent-assisted retrieval therapy within 6 hours
but still died later from subarachnoid hemorrhage. Sec-
ondary stroke prevention strategies after the first stroke
for these patients were also challenging. Fourteen of them
had contraindications for either antiplatelet or antico-
agulant drugs because of severe gastrointestinal bleeding,
hemophagocytic syndrome, and brain surgery with high
risk of bleeding.
Discussion
Our study was the first to describe the pattern of care
of in-house strokes in China. They were predominantly
ischemic strokes and the incidence was around .7% among
admitted patients. Such low rate could be related to the
possibility of under-recognizing and under-reporting of
in-house strokes due to lack of standard protocol and train-
ing of hospital staff.
About half of our in-hospital strokes occurred in pa-
tients admitted to the surgical or cardiology units, a finding
similar to other reports.7,8 Although rare, stroke occurred
as a complication of C E A or intracranial arteriography.9,10
Stroke was also a frequent complication of general surgery,
a finding that is inconsistent with the previous reports.11-13
Providing ongoing stroke education to staff of these de-
partments may help in timely identifying patients with
perioperative strokes.
Our study showed that leukocytosis and elevated glucose
level were common among patients with perioperative
strokes. A recent study reported that infection in hospi-
talized patients was one of the triggers for the development
of acute ischemic stroke.14 These conditions could in-
crease serum viscosity and alter hemodynamic state and
place patients at risk for ischemic strokes. In our study,
risk factors such as stressful condition with or without
concomitant infection, cancer, or hypercoagulable state
commonly coexist.15
At our hospital, stroke patients who came through the
ER had an average door-to-needle time of 53 minutes,
with 60% of them who achieved less than 60 minutes. Their
average onset-to-treatment time was 180 minutes. Com-
pared to stroke patients coming through the ER, it took a
longer time for in-house stroke patients to have a head CT
scan and be seen by a neurologist or stroke doctor. Such
delay has been reported in the literature. One study re-
ported that only 50% of in-house stroke patients had
5
their baseline CT scan within 2 hours of onset. This delay
illustrated that the approach of identifying and triaging
in-house stroke patients was not as organized as for those
coming through the ER. It presents as an opportunity for
improvement. Furthermore, prescribing secondary stroke
prevention therapy for in-house stroke patients was dif-
ficult. Only 5 of 14 patients with large vessel occlusion
were treated because others had contraindications such as
systemic hemorrhages, brain surgery, or other surgeries.
Moreover, 14 of 33 patients could not be on antiplatelet or
anticoagulant drugs because of contraindication.
In conclusion, our finding of perioperation stroke risks
was different from those with no operations. Leukocy-
tosis plus other risk factors showed a trend of increased
risk of having a perioperation stroke, although not sta-
tistically significant. Our study has also shown that even
with the designation of being a comprehensive stroke
center, improvement is still needed to provide timely care
to patients with in-house strokes. Developing an in-
house stroke code and providing education to hospital
staff on stroke recognition are 2 key issues to improve
discovery, triage, and treatment of patients with in-house
strokes.
Acknowledgments: Y.D. and Q.D. designed the study; W.C.,
X.C., and K.F. participated in in-house stroke flow strategy;
and Y.G., X.Z., and B.L. participated in in-house bridging
strategy. Y.D. drafted the manuscript and all other authors
revised the manuscript.
Appendix: Supplementary Material
Supplementary data to this article can be found online
at doi:10.1016/j.jstrokecerebrovasdis.2016.12.017.
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