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W. David Freeman, M.D.,1 Steven B. Dawson, M.D.,1 and Kelly D. Flemming, M.D.2
ABSTRACT
Stroke is the third leading cause of death in the United States, with more
than 140,000 deaths per year. Complications related to stroke resulting in morbidity
and mortality are very common and may result from cerebral and extracerebral causes.
Cerebral causes include cerebral edema, hemorrhagic conversion of an ischemic
infarct, and progression of penumbra to infarction. Extracerebral complications
Stroke-related death 1
and its complications2–26 CEREBRAL COMPLICATIONS OF STROKE
(Fig. 1), can be conceptualized into 2 types: cerebral or
extracerebral (Table 1). Cerebral complications arise Cerebrovascular Pathophysiology
intracranially and occur as part of the subsequent path- An overview of cerebral complications is provided in
ophysiology after the initial stroke, such as a massive Table 1. Ischemia causes brain injury, which manifests as
ischemic stroke leading to swelling, herniation, and neurologic deficits. The type of neurologic deficit de-
brain death. Extracerebral complications after stroke pends on the area of brain affected. Neurons and glia are
are defined by the organ systems affected (e.g., endo- strictly aerobic tissue, with the highest metabolic de-
crinologic, pulmonary, cardiac, gastrointestinal). This mand of all tissues within the human body. The brain
classification of stroke complications is useful, holistic, takes at least 15% of the cardiac output, indicative of its
and helps provide a comprehensive approach in manag- high metabolic demands for oxygen and glucose. Brain
ing stroke patients. tissue without oxygen and glucose quickly depletes intra-
Complications of stroke are largely preventable. cellular ATP and rapidly converts to converting glucose
A simple mnemonic, the ABC’s, can help practitioners to lactate, which produce 2 ATP, compared with up to
remember and treat such complications (Table 2). The 36 ATP from aerobic metabolism. Anaerobic conditions
prevention of these complications is important to re- are intolerable to brain tissue and quickly create an
duce morbidity and mortality from stroke as well and intracellular acidosis, which triggers a cascade of events
serve quality improvement goals. that either lead to programmed cell death, if there are
1
Department of Neurology, Mayo Clinic, Jacksonville, Florida; Semin Neurol 2010;30:501–510. Copyright # 2010 by Thieme
2
Department of Neurology, Mayo Clinic, Rochester, Minnesota. Medical Publishers, Inc., 333 Seventh Avenue, New York, NY
Address for correspondence and reprint requests: W. David 10001, USA. Tel: +1(212) 584-4662.
Freeman, M.D., Mayo Clinic, Cannaday 2 East, Jacksonville, FL DOI: http://dx.doi.org/10.1055/s-0030-1268863.
32224 (e-mail: freeman.william1@mayo.edu). ISSN 0271-8235.
Stroke; Guest Editor, Kelly D. Flemming, M.D.
501
502 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 5 2010
mannitol or hypertonic saline, can be given to reduce patients with ischemic stroke, the CPP should be kept in
ICP,3,18 but often is a temporizing measure. For patients the range of 65 to 70 mm Hg or higher. Cerebral
with symptomatic mass effect, consideration may be perfusion pressure values greater than 130 may lead to
given to hemicraniectomy.3,18 Medical and surgical hyperemia, worsened cerebral edema, or hemorrhage.
management of malignant cerebral edema and the role
of hemicraniectomy in acute cerebral infarction is be-
yond the scope of this review.3,18 It is, however, impor- Recurrent Stroke
tant to remember that to prevent further ischemia, one Recurrent stroke occurs in 9% of patients after an
must maintain CPP. Cerebral perfusion pressure can be initial stroke within the first few weeks.2 (Fig. 1)
calculated once ICP and MAP are obtained from mon- Identification of the underlying stroke mechanism
itoring via the equation, CPP ¼ MAP – ICP. For most and targeting treatment remains the best way to reduce
504 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 5 2010
Table 2 ‘‘ABC’s’’ of Stroke Management (American an embolic event with transient ischemia and subsequent
Heart Association Guidelines)3,18 reperfusion. Seizure, importantly, is no longer an abso-
A–Airway/aspiration, cardiac monitor 24 hour all patients, O2 lute exclusion for tPA.3 Approximately 1 to 2% of stroke
for hypoxic patients, intubation/mechanical ventilation for patients present with status epilepticus.24 Seizures cause
compromised airway—Class I secondary neurologic deterioration after stroke by in-
B–Blood pressure control specific to stroke type—Class II. creasing brain metabolic activity in vulnerable ischemic
Hypotension etiology should be evaluated and treated—Class I brain tissue. Burneo et al found that patients with
C–CPP (measure and control ICP if elevated)—Class II seizures had a higher mortality at 30 days (36.2% vs
D–DVT prevention with compression devices—Class I, if no 16.8%, p < 0.0001), at 1-year poststroke (48.6% vs
active bleeding risk, then consider SQ UFH or LMWH-Class II 27.7%, p < 0.001), had a longer hospitalization, and
E–Early mobilization—Class I greater disability at discharge (p < 0.001).23 Risk factors
F–Fever worked up & treated aggressively—Class I for seizure after stroke by multivariate analysis included
G–Glucose > 140 – 185 mg/dL, use insulin; hypoglycemia stroke severity, hemorrhagic stroke subtype, and the
should be treated—Class I presence of neglect on neurologic exam. The authors
CPP, cerebral perfusion pressure; DVT, deep vein thrombosis; ICP,
concluded that seizures after stroke increased resources
intracranial pressure; LMWH, low-molecular-weight heparin; SQ, utilization, hospital length of stay, and increased both
subcutaneous; UFH, unfractionated heparin. 30-day and one-year mortality. Recurrent seizures de-
velop in 2% to 33% of poststroke patients, particularly of
was 0.5% compared with 0.8% in those not allocated to confirmed a role for heparin in prevention of VTE.
receive heparin. There was no significant difference in Treatment with LMWH was associated with significant
the rate of PE in those allocated to aspirin versus those reductions in DVT and PE; however, there was an
that did not receive it. The rate of major hemorrhage increase in major extracranial hemorrhage. The studies
in the heparin group was 1.3% compared with 0.4% in included in this meta-analysis, however, were designed
those not receiving heparin. mainly around the primary endpoint of stroke outcome
A meta-analysis of studies evaluating low-molec- and reduction of recurrent stroke. Thus, VTE was a
ular-weight heparin (LMWH) in acute ischemic stroke secondary endpoint.
THE ABC’S OF STROKE COMPLICATIONS/FREEMAN ET AL 507
The PREVAIL (Prevention of Venous Although the study reported a reduction in DVT in the
Thromboembolism after Acute Ischemic Stroke) Trial28 stockings group, the reduction was not significant.30
was the largest trial comparing LMWH enoxaparin Pneumatic sequential compression devices (SCDs)
40 mg subcutaneously daily against UFH 5000 IU every are best studied in postoperative patients and less well
12 hours in 1,762 nonambulatory ischemic stroke pa- studied in patients with stroke.31 SCDs can be used in
tients. The rates of symptomatic DVT between the combination with UFH or LMWH for high-risk DVT
LMWH group and the UFH group were not signifi- patients; however, there is no evidence to suggest added
cantly different (p ¼ 0.18). However, the rates of asymp- benefit or harm. These devices used alone are best
tomatic DVT detected by ultrasound were statistically reserved for patients who cannot receive anticoagulants.
less prevalent in the low-molecular-heparin group versus Some patients may require an inferior vena cava
the unfractionated heparin group (p < 0.0001). The rate (IVC) filter (Fig. 4). According to the American Heart
of symptomatic ICH in each group was 1% (n ¼ 4 Association guidelines,3,18 ischemic stroke patients who
occurred on enoxaparin, 3 of whom died) compared cannot receive anticoagulants and have a confirmed
with n ¼ 6 on UFH, 4 of whom died, which was not DVT should be considered for an IVC filter. It is
statistically significant. Higher initial NIH Stroke Scale important to note that little data exists regarding the
(e.g., > 14) predicted bleeding. Symptomatic extracra- long-term safety of IVC filters, the ability for the filter to
nial bleeding was 1% in enoxaparin group (2 fatal) and prevent small emboli, and the length of time the filter
0% in UFH. should be left in place.3 Complications from IVC filters
Stroke and coronary artery disease (CAD) are also stroke severity, female sex, and use of urinary catheters.3
comorbidities.35,36 Stroke risk is highest within 3 months Bacteriuria is common in catheterized patients; thus, a
of a MI.35,36 One third of stroke patients have CAD (or diagnosis of UTI in catheterized patients requires a
silent CAD).35,36 Three percent of stroke patients die culture in addition to the urinalysis. Prevention is key
from cardiac event in less than 90 days. In addition, in stroke patients. Overuse of catheters is common. This
stroke may be the presenting sign of an MI in a small can be simply overcome by reviewing the daily need for a
percentage of patients (ventricular dysfunction). To urinary catheter, as well as other invasive lines, and
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