Acute Stroke Treatment
Stroke Society of the Philippines
Rm. 1403 14/F North Tower, Cathedral Heights Bldg. Complex
St. Luke’s Medical Center, E. Rodriguez Sr. Ave., Quezon City
Telephone No.: (632) 723-0101 Loc 5143
Telefax No.: (632) 722-5877
E-mail: ssp_secretariat@yahoo.com
Website: www.strokesocietyphil.org
Board of Trustees 2010-2012
President
1st Vice-President
2nd Vice-President
Secretary
Treasurer
Public Relation Officer
Immediate Past President
Members
Carlos L. Chua, MD
Artemio A. Roxas, Jr., MD
Maria Cristina Z. San Jose, MD
Ma. Epifania V. Collantes, MD
Betty D. Mancao, MD
Pedro Danilo J. Lagamayo, MD
Ester S. Bitanga, MD
Raquel M. Alvarez, MD
Alejandro C. Baroque II, MD
Romulo U. Esagunde, MD
Johnny T. Lokin, MD
Manuel M. Mariano, MD
Dante D. Morales, MD
Orlino A. Pacioles, MD
Peter P. Rivera, MD
Ma. Socorro F. Sarfati, MD
Stroke: Think Globally, Act Locally
Principles:
1. Stroke is a “brain attack”
...needing emergency management, including specific treatments and secondary and
tertiary prevention.
2. Stroke is an emergency
...where virtually no allowances for worsening are tolerated.
3. Stroke is treatable
...optimally, through proven, affordable, culturally-acceptable and ethical means.
4. Stroke is preventable
...in implementable ways across all levels of society.
The recommendations contained in this document are intended to merely guide practitioners in the prevention, treatment and rehabilitation of patients
with stroke. In no way should these recommendations be regarded as absolute rules, since nuances and peculiarities in individual patients, situations or
communities may entail differences in specific approaches. The recommendations should supplement, not replace, sound clinical judgments on a caseto-case basis.
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Acute Stroke Treatment
­
Background and Rationale for Simpli­
fied Initial Classification of Acute
Stroke Based on CLINICAL Severity
There are various ways to classify stroke such as based
on stroke type, localization, brain and vascular territory
involvement, patho-mechanism and time course. However utilization of some of the standardized classification
schemes may be difficult & time-consuming especially for
non-neuroscience specialists in an acute stroke setting.
The working committee of the first edition (1999) of the
SSP Stroke Handbook has developed a practical & local­ly
relevant initial classification scheme which is based simply on observed severity of patient’s neurological deficits,
including level of sensorium and response to pain. The
present 2010 working committee still finds this format
useful particularly in the acute setting, reliable for both
medical and paramedical personnel and advocates its
continued use to help direct crucial actions and decisions
at the emergency room.
After initial stabilization & management, additional workups are recommended for determination and further
classification of patients based on underlying stroke
patho-mechanism which is necessary for selection of
appropriate secondary prevention strategies.
­Definition of Stroke Severity
MILD
STROKE
MODERATE
STROKE
Alert patients with Awake patient
any or a combina- with significant
tion of the followmotor and/ or
ing:
sensory and/ or
visual deficit
1. Mild pure motor weakness of one
or
side of the body,
defined as: can Disoriented,
raise arm above drowsy or light
shoulder, has
stupor with
clumsy hand, or purposeful
can ambulate with- response to
out assistance
painful stimuli
2. Pure sensory deficit
3. Slurred but intel ligible speech
4. Vertigo with inco ordination (e.g.,
gait disturbance,
unsteadiness
or clumsy hand)
5. Visual field
defects alone
or
NIHSS
score = 0 – 5
See Guidelines
for TIA and
Mild Stroke
or
SEVERE
STROKE
Deep stupor or
comatose patient
with non-purposeful response,
decorticate, or
decerebrate
posturing to
painful stimuli
or
Comatose
patient with
no response to
painful stimuli
or
NIHSS
NIHSS
score = 6 - 21
score >22
See Guidelines See Guidelines
for Moderate
for Severe
Stroke
Stroke
­
Guidelines for TIA
(For detailed discussions on TIA, please see Chapter IV)
Ascertain clinical diagnosis of TIA
Management (history and physical exam are very
Priorities
important)
• Exclude common stroke mimickers
Provide basic emergent supportive
care (ABCs of Resuscitation)
Monitor neuro-vital signs, BP, MAP,
RR, temperature, pupils
Perform stroke scales (NIHSS, GCS)
Perform risk stratification using the
ABCD2 Scale
Monitor and manage BP, treat if
MAP >130
Precautions:
• Avoid precipitous drop in BP (not
>15% of baseline MAP). Do not use
rapid-acting sublingual agents; when
needed, use easily titratable IV or
short acting oral antihypertensive
medication.
• Ensure appropriate hydration.
Recommended IVF - 0.9% NaCl
if needed.
Emergent
•
Diagnostics •
•
•
•
Complete blood count (CBC)
Blood sugar (CBG or RBS)
Electrocardiogram (ECG)
PT/PTT
Cranial MRI-DWI as soon as
possible is preferred. May do
Non-contrast Cranial CT scan if
MRI is not possible.
Non-cardio-Cardioembolic
embolic
Aspirin 160-325
Early
mg/day. start
Specific
as early as
Treatment
possible and
continue for
14 days
For secondary
prevention,
see under
"Delayed
Management
and Treatment"
Consider careful
anticoagulation
with IV heparin or
SQ low molecularweight heparin
(LMWH) for those
at high risk for early
recurrence (e.g.,
AF with thrombus,
valvular heart
disease or MI)
Neuroprotection
Aspirin 160-325
mg/day (if anticoagulation is not
possible or contraindicated)
If infective endocarditis is suspected,
give antibiotics and
do not anticoagulate.
or
Neuroprotection
Acute Stroke Treatment
Admit to Hospital (Stroke Unit)
Place of
1.
Treatment
2.
3.
4.
TIA within 48 hours
Crescendo TIAs (multiple & increasing
symptoms)
TIA with known high risk cardiac source of
embolism, known hypercoagulable state
or symptomatic ICA stenosis
Patient with ABCD2 score of >3
Non-cardioembolic
(Thrombotic/Lacunar)
Urgent Outpatient Work-up
TIA >2 weeks (but work-ups should be
done within 24 – 48 hours)
Cardioembolic
Delayed
Antiplatelets (aspirin, clopidogrel,
Echocardiography
Management
cilostazol, triflusal, dipyridamole,
and/or cardiology
and
extended-release dipyridamole +
consult
Secondary
aspirin combination)
Prevention
If age <75 and PT/INR
Control of risk factors
available, anticoagu
lation with warfarin
Recommended vascular studies
(target INR: 2-3)
such as carotid ultrasound to document extracranial stenosis.
If age >75, warfarin
If this reveals >70% stenosis, refer
(target INR: 2.0
to neurologist/neurosurgeon/
[1.6-2.5])
vascular surgeon for decision-
making regarding CEA or
If anticoagulation is
stenting
contraindicated, give
antiplatelets (ASA
To document intracranial stenosis,
160 mg-325 mg)
recommend either TCD or MRA or
CTA
­
Others
Specialized coagulation
tests such as screening
for hypecoagulable states
(protein C, protein S,
antithrombin III, fibrinogen,
homocysteine) and drug
screening (e.g., metam-
phetamine, cocaine) can be
considered for young patients with TIA especially
when no vascular risk factors exist and no underlying cause is identified
If vasculitis is suspected,
may do ESR, ANA, Lupus
anticoagulant testing
Transesophangeal echocardiography (TEE) to rule
out PFO
Guidelines for Mild Stroke
Management
Priorities
Ascertain clinical diagnosis of stroke (history and physical exam are very important)
• Exclude common stroke mimickers
• Provide basic emergent supportive care (ABCs of resuscitation)
• Monitor neuro-vital signs, BP, MAP, RR, temperature, pupils, O2 saturation
• Perform and monitor stroke scales (NIHSS, GCS)
• Provide O2 support to maintain O2 saturation >95%
• Monitor and manage BP; treat if MAP >130
Precautions:
• Avoid precipitous drop in BP (not >15% of baseline MAP). Do not use rapid-acting
sublingual agents; when needed use easily titratable IV or oral antihyper­tensive
medication.
• Ensure adequate hydration. Recommended IVF - 0.9% NaCl.
Emergent
Diagnostics
•
•
•
•
•
•
Complete Blood Count (CBC)
Blood Sugar (CBG or RBS)
Electrocardiogram (ECG)
PT/PTT
Non-contrast CT scan of the brain or MRI-DWI as soon as possible
If ICH, compute for hematoma volume
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Acute Stroke Treatment
IschemicHemorrhagic
Early Specific
Non-cardioembolic
Cardioembolic
Treatment
(Thrombotic, Lacunar)
Aspirin 160-325 mg/day start as
Consider careful anti
early as possible and continue
coagulation with IV
for 14 days
heparin or SQ low mole
cular-weight heparin
CT-scan
For secondary prevention, see
(LMWH) for those high
confirmed
under "Delayed Management and
risk with early recurrence
Treatment"
(e.g., AF with thrombus,
valvular heart disease
Neuroprotection
or MI)
Early rehabilitation once stable
or
within 72 hours
Aspirin 160-325 mg/day
(if anticoagulation is not
possible or contra
indicated)
Neuroprotection
(Appendix V-D)
Early rehabilitation once
stable within 72 hours
If infective endocarditis
is suspected, give
antibiotics and do
not anticoagulate
Early neurology and/ or
neuro­ surgeon consult for all ICH is recommended
Monitor and maintain BP: Target MAP of 110 or SBP
of 160
Neuroprotection
Early rehabilitation once stable within 72 hours
Give anticonvulsants for clinical seizures and proven
subclinical or electrographic
seizures. Prophylactic
AEDs are generally not recommended
Steroids are not recom-
mended
Monitor and correct meta-
bolic parameters
Correct coagulation/bleed-
ing abnormalities
Follow recommendations for neurosurgical interven-
tion
For aneurysmal SAH, refer
to specific chapter
Place of Admit to Hospital: Acute Stroke unit/Regular Room
treatment
IschemicHemorrhagic
Delayed Non-cardioembolic
Cardioembolic
Management
(Thrombotic, Lacunar)
and Treatment
(Secondary
Antiplatelets (aspirin, clopidogrel,
Echocardiography and/
Prevention)
cilostazol, triflusal, dipyridamole,
or cardiology consult
extended-release dipyridamole +
aspirin combination)
If age <75 and PT/INR
available, anticoagula
Control of risk factors
tion with warfarin
(target INR: 2-3)
Recommended vascular studies
such as carotid ultrasound to
If age >75, warfarin
document extracranial stenosis.
(target INR: 2.0 [1.6-2.5])
If this reveals >70% stenosis, refer
to neurologist/neurosurgeon/vascular
If anticoagulation is
surgeon for decision-making
contraindicated, give
regarding CEA or stenting
antiplatelets (ASA 160
mg-325 mg)
To document intracranial stenosis,
recommend either TCD or MRA
or CTA
Long-term strict BP control
and monitoring
Consider contrast CT
scan, 4 vessel cerebral
angiogram, MRA or CTA
if patient is:
1) <45 years old,
2) normotensive
3) has lobar ICH
4) uncertain cause of ICH
5) suspected to have
aneurysm, AV malformation
or vasculitis
Acute Stroke Treatment
­
Guidelines for Moderate Stroke
Ascertain clinical diagnosis of stroke (history and physical exam are very important)
Management
• Exclude common stroke mimickers
Priorities Basic emergent supportive care (ABCs of resuscitation)
Neuro-vital signs, BP, MAP, RR, temperature, pupils, oxygen saturation
Perform and monitor stroke scales (NIHSS, GCS)
Monitor and manage BP. Treat if MAP >130
Provide O2 support to maintain O2 saturation >95%
• Precaution: Avoid precipitous drop in BP (not >15% of baseline MAP). Do not use rapid-acting
sublingual agents; when needed use easily titratable IV or oral antihypertensive medication.
Identify comorbidities (cardiac disease, diabetes, liver disease, gastric ulcer, etc.)
Recognize and treat early signs and symptoms of increased ICP
Ensure adequate hydration. Recommended IVF-0.9% NaCl
Emergent
Diagnostics
•
•
•
•
CBC with platelet count
•
CBG or RBS
•
PT/PTT
Serum Na+ and K+
•
Early Specific
Treatment
ECG
Non-contrast CT scan of brain or
MRI-DWI as soon as possible
If ICH, compute for hematoma volume
IschemicHemorrhagic
Non-cardioembolic
(Thrombotic, Lacunar)
Cardioembolic
If within 3 hours of stroke onset,
If within 3 hours of
Early neurology and/ or
consider IV recombinant tissue
stroke onset, consider
neurosurgical consult for all
plasminogen activator (rt-PA) and
IV rt-PA and refer to
ICH is recommended
refer to neuro specialist
neuro specialist
Monitor and maintain BP.
CT-scan
Selected patients within
If within 6 hours of
Target MAP = 110 mmHg
confirmed
3 – 4.5 hour time window may
stroke onset and in
or SBP = 160 mmH
benefit with IV recombinant tissue
specialized centers,
plasminogen activator (see section
consider IA thrombolysis Neuroprotection
on thrombolytic therapy)
If rt-PA ineligible or 24
Give anticonvulsants for
hours after rt-PA treatclinical seizures and proven
ment consider either care- subclinical or electrographic
ful anticoagulation with
seizures. Prophylactic
AEDs are generally not
Refer to neurologist for evaluation
IV heparin or SQ
recommended
& decision.
LMWH for those at high
risk for early recurrence Steroids are not
If within 6 hours of stroke onset
or ASA 160-325 mg/day recommended
and in specialized centers,
consider intra-arterial (IA)
Neuroprotection
Monitor and correct
thrombolysis
metabolic parameters
Start ASA 160-325 mg 24 hours
Early supportive
after rtPA treatment.
rehabilitation
If rtPA ineligible, start Aspirin
If infective endocarditis
160-325 mg/day as soon as
is suspected, give
possible
antibiotics and do not
anticoagulate
Neuroprotection
Early supportive rehabilitation
Consider early decompressive
Hemicraniectomy for large
malignant MCA infarction
Correct coagulation/
bleeding abnormalities
Follow recommendations
for neurosurgical
intervention
Early rehabilitation once
stable
For aneurysmal SAH, refer
to specific chapter
Place of Hospital - Intensive Care Unit or Stroke Unit
Treatment
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Acute Stroke Treatment
IschemicHemorrhagic
Delayed Non-cardioembolic
Cardioembolic
Management
(Thrombotic, Lacunar)
and Treatment
(Secondary
Antiplatelets (aspirin, clopidogrel,
Echocardiography and/
Prevention)
cilostazol, triflusal, dipyridamole,
or cardiology consult
extended-release dipyridamole +
aspirin combination)
If age <75 and PT/INR
available, anticoagu
Control of risk factors
lation with warfarin
(target INR: 2-3)
Recommended vascular studies
such as carotid ultrasound to
If age >75, warfarin
document extracranial stenosis.
(target INR: 2.0 [1.6-2.5])
If this reveals >70% stenosis, refer to neurologist/neurosurgeon/
If anticoagulation is
vascular surgeon for decisioncontraindicated, give
making regarding CEA or stenting
antiplatelets
(ASA 160-325 mg)
To document intracranial stenosis, recommend either TCD or MRA
or CTA.
­
Long-term strict BP control
and monitoring
Consider contrast CT scan,
4 vessel cerebral angiogram, MRA or CTA if
patient is:
1) <45 years old,
2) normotensive
3) has lobar ICH
4) uncertain cause of ICH
5) suspected to have
aneurysm, AV
malformation or
vasculitis
Guidelines for Severe Stroke
Ascertain clinical diagnosis of stroke (history and physical exam are very important)
Management
• Exclude common stroke mimickers
Priorities Basic emergent supportive care (ABCs of resuscitation)
Neuro-vital signs, BP, MAP, RR, temperature, pupils, oxygen saturation
Perform and monitor stroke scales (NIHSS, GCS)
Monitor and manage BP; treat if MAP >130
Provide O2 support to maintain O2 saturation >95%
• Precaution: Avoid precipitous drop in BP (not >15% of baseline MAP). Do not use rapid acting sublingual agents; when needed use easily titratable IV or oral antihypertensive
medication.
Identify comorbidities (cardiac disease, diabetes, liver disease, gastric ulcer, etc.)
Recognize and treat early signs and symptoms of increased ICP
Ensure adequate hydration. Recommended IVF-0.9% NaCl
Emergent
Diagnostics
10
•
•
•
•
•
•
•
CBC with platelet count
CBG or RBS
PT/PTT
Serum Na+ and K+
ECG
Non-contrast CT scan of brain or MRI-DWI as soon as possible
If ICH, compute for hematoma volume
Acute Stroke Treatment
IschemicHemorrhagic
EarlyNon-cardioembolic
Supportive treatment:
Specific
(Thrombotic, Lacunar) Cardioembolic
1. Mannitol 20%
Treatment 0.5-1g/ kgBW
May give aspirin
May give aspirin q 4-6 hours for 3-7 days
160-325 mg/day
160-325 mg/day
2. Neuroprotection
Refer to neuro specialist cases
Refer to neuro specialist
of posterior circulation strokes
cases of posterior
3. Give anticonvulsants for
within 12 hours of onset for
circulation strokes clinical seizures and
CT-scan
evaluation and decision regarding
within 12 hours of proven subclinical or
confirmed
thrombolytic therapy.
onset for evaluation electrographic seizures.
and decision regarding Prophylactic AEDs are
Neuroprotection
thrombolytic therapy generally not recom mended
Neuroprotection
If cerebellar infarct, consult
If cerebellar infarct,
Neurosurgery consult if:
neurosurgeon as soon as possible
consult neurosurgeon
1. Patient not herniated; as soon as possible Lobar bleed or located
Early supportive rehabilitation in putamen, pallidum,
Early supportive cerebellum;
rehabilitation
Family is willing to
accept consequences
of irreversible coma as
persistent vegetative
state
Goal is reduction of mortality
2. ICP monitoring is contem plated and salvage
surgery is considered
Early supportive
rehabilitation
Place of
Treatment
Intensive Care Unit
Delayed
Discuss prognosis with relatives of the patient in a most compassionate manner
Management
and
IschemicHemorrhagic
Treatment
(Secondary Non-cardioembolic
Prevention)
(Thrombotic, Lacunar) Cardioembolic
Antiplatelets (Aspirin, clopidogrel,
Echocardiography and/
Long-term strict BP control
cilostazol, triflusal, dipyridamole,
or cardiology consult
and monitoring
extended-release dipyridamole +
aspirin combination)
If age <75 and PT/INR
Consider contrast CT scan,
available, anticoagula4 vessel cerebral angio
Control of vascular risk factors
tion with warfarin (target gram, MRA or CTA
INR: 2-3)
if patient is:
If age >75, warfarin
1) <45 years old,
(target INR: 2.0 [1.6-2.5]) 2) normotensive
3) has lobar ICH
If anticoagulation is
4) uncertain cause of ICH
contraindicated, give
5) suspected to have
antiplatelets
aneurysm, AV
(ASA 160 mg-325 mg)
malformation or
vasculitis
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11
Acute Stroke Treatment
Early Specific Treatment for Ischemic Stroke
I. Antithrombotic Therapy in Acute Stroke
Drug
Trial
DesignResult
Aspirin treated patients had
slightly fewer deaths at 14 days,
significantly fewer recurrent
ischemic strokes at 14 days
and no excess of hemorrhagic
strokes
Chinese Acute Stroke Trial
(CAST, Lancet 1997;449:
1641-1649)
21,106 patients with acute
ischemic stroke within 48 hours
were randomized to Aspirin
160 mg OD or placebo for up
to 4 weeks
Aspirin significantly reduced
the risk of recurrent stroke or
vascular death
Fast assessment of Stroke
392 patients with TIA or minor
and Transient Ischemic Attack
stroke within 24 hours were
to Prevent Early Recurrence,
randomized to Clopidogrel
(FASTER, Lancet Neurology
(300 mg loading dose then
2007; 6:961-969)
75 mg/day plus Aspirin 81 mg
or Aspirin 75 mg alone, with or
without Simvastatin (in factorial
design) and followed up for
90 days)
The trial was prematurely
terminated because of failure
to recruit patients at the prespecified recruitment rate
because of increased use
of statins
Hemorrhagic events were
higher with the combination
treatment
Meta-analysis of randomized
Ten trials involving 2885
controlled trials on low
patients with acute ischemic
molecular weight heparins
stroke
and heparins in acute ischemic
stroke
Low molecular weight heparin
(Stroke 2000;31:31:1770-1778) or heparinoids given within
7 days of stroke
The use of LMWH/heparinoids
was associated with significant
reduction in venous thromboembolism (DVT and PE).
However, it had no significant
effect on reducing death
and disability at 6 months
LMWH
Clopidogrel-ASA vs Aspirin
Aspirin
International Stroke Trial
19,435 patients with acute
(IST, Lancet 1997; 349:
ischemic stroke were
1569-1581)
randomized within 48 hrs to
Aspirin 300 mg day, subcuta
neous heparin 5000 units BID
or 12,500 units BID, Aspirin
plus heparin or neither
II. Neuroprotection and Neuroprotectant Drugs
A. NEUROPROTECTIVE INTERVENTIONS
The 5 “H” Principle
AVOID hypotension, hypoxemia, hyperglycemia
or hypoglycemia and hyperthermia (fever) during
acute stroke in an effort to “salvage” the ischemic
penumbra.
Avoid Hypotension and allow Permissive Hypertension during the 1st 7 days
• Aggressive BP lowering is detrimental in
12
For patients receiving heparin,
there were fewer deaths or
recurrent strokes; however
there were more hemorrhagic
strokes & serious extracranial
hemorrhage, mostly in the
higher dose heparin group,
resulting in no net benefit.
Recurrent stroke at 90 days
were: Clopidogrel-ASA (7.1%),
Aspirin alone (10.1%),
absolute risk reduction of
3.8% p=0.19
acute stroke. Manage hypertension as per
recommendation.
Avoid Hypoxemia
• Routine oxygenation in all stroke patients is
not warranted
• Maintain adequate tissue oxygenation (target
O2 saturation >95%)
• Do arterial blood gases (ABG) determination
or monitor oxygenation via pulse oximeter
• Give supplemental oxygen if there is evidence
of hypoxemia or desaturation
• Provide ventilatory support if upper airway is
threatened or sensorium is impaired or ICP
is increased.
Acute Stroke Treatment
Avoid Hypoglycemia or Hyperglycemia
Background: Hyperglycemia can increase
the severity of ischemic injury (causes lactic
acidosis, increases production of free radicals,
worsens cere­bral edema and weakens blood
vessels), whereas hypoglycemia can mimic a
stroke.
• Prompt determination of blood glucose should
be done in all stroke patients
• Ensure glycemic control at 110-180 mg/dL
preferably within the first 6 hours and maintain up to 3-5 days. May start intervention
with insulin if CBG >180 mg/dL
• Avoid glucose-containing (D5) IV fluids. Use
isotonic saline (0.9% NaCl)
Avoid Hyperthermia
Background: Fever in acute stroke is associated
with poor outcome possibly related to increased
metabolic demand, increased free radical
production and enhanced neurotransmitter
release.
Hyperthermia increases the relative risk of 1
year mortality by 3.4 times.
• For every 1oC increase in body temperature, the relative risk of death or disability
increased by 2.2
Hypothermia can reduce infarct size by 44% in
animal studies
• Search for the source of fever
• Treat fever with antipyretics and cooling
blankets
• Maintain normothermia.
B. NEUROPROTECTANT DRUGS:
Neuroprotectants are drugs with multi-modal
action:
• Protect against excitotoxins and help prolong
neuronal survival
• Block the release of glutamate and inflammatory cytokines, inhibit the formation of free
radicals and apoptosis
Over 50 neuroprotective agents such as glutamate, NMDA/AMPA antagonists, calcium channel
blockers, free radical scavengers have undergone
phase III clinical trials but most have failed. Several
reasons have been raised to explain the apparent disappointments: animal models were wrong,
human trials were not done optimally (e.g., determination of time window, patient heterogeneity,
“targeted” neuroprotection which addresses single
mechanism of neuronal injury at a time, exclusion of concomitant treatment with thrombolytic
agents).
Among the various pharmacologic agents investigated, CDP-choline (Citicoline) has shown great
promise as evidenced by numerous experimental
studies showing consistent improved functional outcome and reduced infarct size in animal models of
stroke. Several trials in ischemic and hemorrhagic
strokes conducted worldwide have documented
its excellent safety profile. In individual patient
data pooling analysis (4 trials, 1652 patients) oral
citicoline given within the first 24 hours of moderate
to severe ischemic stroke significantly increased the
probability of global recovery by 30% at 3 months.
Similar positive result in reduction in death and
disability from acute ischemic stroke was obtained
in the latest meta-analysis in 2008.
CDP-choline has multimodal effects on the
ischemic and reperfusion cascade. It helps increase
phosphatidylcholine synthesis for membrane
stabilization and repair. It inhibits the activation of
phopholipase A2 and reduces oxygen free radicals
and inflammatory cytokines within the injured brain
during ischemia.
A randomized double-blind placebo controlled trial
on safety and efficacy of Citicoline 1 gm twice a day
in acute ischemic stroke within 24 hours for 6 weeks
known as International Citicoline on Acute Stroke
or ICTUS is currently underway to confirm results
of the pooled data analysis and meta-analysis.
The use of neuroprotectants in acute stroke
remains a matter of preference by the attending physician. The choice of Citicoline is a
reasonable option.
Two other pharmacologic agents with putative
neuroprotective properties are currently undergoing or recently completed phase III clinical
trials.
An international, multicenter double blinded,
placebo controlled randomized controlled trial on
Neuroaid known as Chinese Medicine Efficacy in
Stroke Recovery or CHIMES among patients with
acute ischemic stroke within 72 hours is currently
ongoing in several countries in Asia including Singa­
pore, Philippines, Thailand, Korea, Sri Lanka.
A double-blinded placebo controlled randomized
clinical trial to evaluate the safety and efficacy of
Cerebrolysin in patients with Acute Ischemic Stroke
in Asia in ASIA (CASTA) was recently completed
with results due this year.
Bibliography:
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mechanisms in cerebral ischemia. J. Neurochem 2002:80 :12-23
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of poststroke hyperglycemia using continuous glucose monitoring.
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3. Azzimondi G, Bassein L, Nonino F. et al. Fever in acute stroke worsens
prognosis: A prospective study. Stroke 1995;26:2040-2043
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prognosis of stroke in nondiabetic and diabetic patients: A systematic
overview. Stroke 2001; 32:2426-2432.
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brain damage in acute ischemic stroke. Stroke 1998;29:2455-2460.
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ischemic stroke: an individual patient data pooling analysis of clinical
trials. Stroke 2002;33:2850-2857.
8. Davalos A. ICTUS study: International Citicoline Trial on Acute Stroke
(NCT00331890)
9. Diringer M, Reaven N, Funk, S and Uman G. Elevated body temperature
independently contributes to increased length of stay in neurologic
intensive care unit patients. Critical care Medicine 2004; 32:14891495.
10. Hajat, Cother, Hajat, S, Sharma, P. Effect of postroke pyrexia on stroke
outcome. Stroke 2000; 31:410.
11. Hong Z. Bornstein N, Brainin M and Heiss WD. A double blind
placebo controlled randomized trial to evaluate the safety and efficacy
of Cerebrolysin in patients with acute ischemic stroke (CASTA).
www.TheFilipinoDoctor.com l Sign up and open your clinic to the world.
13
Acute Stroke Treatment
International Journal of Stroke 2009;4:406-412.
12. Hurtado O, Cardenas A, Pradillo JM et al. A chronic treatment with CDP
choline improves functional recovery and increases neuronal plasticity
after experimental stroke. Neurobiology of disease 2007;26:105-111.
13. Kammersgaard LP, Jorgensen HS, Rungby JA et al. Admission body
temperature predicts long-term mortality after acute stroke. Stroke
2002; 33:1759-1762.
14. Kresel S, Alonso, A, Szabo K and Hennerici, M et al. Sugar and niceaggressive hyperglycemic control in ischemic stroke and what can
we learn from non-neurological intensive glucose control trials in the
critically ill. Cerebrovasc Dis 2010; 29:518-522
15. Labiche LA, Grotta JC. Clinical trials for cytoprotection in stroke.
NeuroRx 2004;1:46-70.
16. Lisberg P and Roine R. Hyperglycemia in Acute Stroke. Stroke 2004.
35:363-364.
17. Lizasoain I, Cardenas A, Hurtado O. et al. Targets of cytoprotection in
acute schemic stroke: present and future. Cerebrovasc Dis 2006: 21
(suppl 2)1-8.
18. Layden P, Wahlgren N. Mechanism of action of neuroprotectants in
stroke. Journal of stroke and cerebrovascular diseases. 2000; 9 (6):
9
19. Quin TJ and Lees KR. Hyperglycemia in acute stroke – to treat or not
to treat. Cerebrovasc Dis 2009; 27 suppl 1:148-155.
20. Secades J. and Lorenzo J. Citicoline: Pharmacological and clinical
review 2006 update: Methods and findings in experimental and clinical
pharmacology 2006:26 (suppl B): 1-56.
21. Venketasubramanian N, CL Chen, R. Gan, et al. on behalf of the
CHIMES Investigators, A double-blind, placebo-controlled, randomized,
multicenter study to investigate CHInese Medicine Neuroaid Efficacy
on Stroke recovery (CHIMES Study). International Journal of Stroke
2009;4:54-60
III. Anticoagulation In Acute Cardio­
embolic Stroke
A.Cardioembolic Sources
High Risk
Low or Uncertain Risk
AF (valvular or
Mitral valve Prolapse
non-valvular)
Rheumatic mitral
Mitral annular calcification
stenosis
Prosthetic heart
Patent foramen ovale valves (PFO)
Recent MI
Atrial septal aneurysm
LV/LA thrombus
Calcific aortic stenosis
Atrial myxoma
Mitral valve strands
Infective Endocarditis
Dilated cardiomyopathy
Marantic endocarditis
B. Indications and contraindications for anticoagulation in patients with Cardioembolic Stroke
Probably IndicatedContraindicated
Intracardiac thrombus Bleeding diathesis
Mechanical prosthetic Non-petechial intracranial
valve hemorrhage
Recent MI
Recent major surgery
or trauma
CHF
Infective endocarditis
Bridging measure for
long term anticoagu lation
14
C. When considering anticoagulation in acute
cardio­embolic stroke, the benefits of anti­
coagulation in reducing early stroke recurrence
should be weighed against the risk of hemorrhagic transformation. The latter is higher in
patients with large infarction, severe strokes
or neurological deficits and uncontrolled hyper­
tension.
D.How to anticoagulate
1. Requirements for IV anticoagulation of patients
with cardiogenic source of embolism:
a. Heparin sodium in D5W
b. Infusion pump, if available
c. Activated partial thromboplastin time (aPTT)
or clotting time
2. Procedure:
a. Start intravenous infusion at 800 units
heparin/hour ideally using infusion pump. IV
heparin bolus is not recommended.
b. Perform aPTT as often as necessary, every 6
hours if needed, to keep aPTT at 1.5-2.5x the
control. Risk for major hemorrhage, including
intracranial bleed, progressively increases as
aPTT exceeds 80 seconds.
c. Infusion may be discontinued once oral
anticoagulation with warfarin has reached
therapeutic levels or once antiplatelet medication is started for secondary prevention.
To date, there has been no trial directly comparing effi­
cacy of unfractionated heparin vs LMWH in patients with
acute cardioembolic stroke. LMWH has the advantage
of ease of administration and does not require aPTT
monitoring.
Bibliography
1. Adams H. Emergent use of anticoagulation for treatment of patients with
ischemic stroke. Stroke 2002;33:856-861.
2. Hart R, Palacio S, Pearce L. Atrial fibrillation, stroke and acute
antithrombotic therapy. Stroke 2002;33:2722-2727.
3. Moonis, M, Fisher M. Considering the role of heparin and low-molecular
weight heparin in acute ischemic stroke. Stroke 2002;33:1927-1933.
4. Paciaroni M, Agnelli G, Micheli S. et al. Efficacy and safety of
anticoagulant treatment in acute cardioembolic stroke: A meta-analysis
of randomized controlled trials. Stroke 2007; 38: 423-430.
Acute Stroke Treatment
IV. ADIMINITRATION of rt-PA to ACUTE ISCHEMIC STROKE PATIENTS
Randomized Trials on Intravenous rt-PA Therapy in Acute Ischemic Stroke
Trial
NINDS tPA trial: National Institute
of Neurological Disorders and
Stroke tPA trial (N Eng J Med
1995;333:1581 - 1587)
DesignResults
291 patients with acute ischemic
stroke <3 hours were randomized
to tpa (0.9 mg/kg IV) or placebo
and assessed for 4-point
improvement in NIH stroke scale
or the resolution of neurological
deficit within 24 hours; 333
patients received IV rt-PA within
3 hours of symptom onset and
were assessed for functional and
clinical outcome for 3 months
ECASS: European Australasian
620 patients with acute ischemic
Cooperative Acute Stroke Study
stroke <6 hours were randomized
(JAMA 1995;274:1017-1025)
to tPA 1.1 mg/kg or placebo
ECASS II: Second European
800 patients with acute ischemic
Australasian Cooperative Acute
stroke <6 hours were randomized
Stroke Study (Lancet 1998;352:
to tPA 0.9 mg/kg or placebo
1245-1251)
No difference in neurologic
improvement at 24 hours, but
patients given IV rt-PA were
30% more likely than controls to
have minimal or no disability at
3 months, despite more symptomatic ICH (6.4% vs 0.6%).
Overall, there was no difference
in mortality in 3 months.
No difference in disability using
intention to treat analysis.
However, there were 109 major
protocol violations. Post hoc
analysis excluding these patients
indicated better recovery for tPA
group at 90 days
No significant difference was
seen in the rate of favorable
outcome at 3 months between
rt-PA and placebo treated group
ATLANTIS A: Alteplase
142 patients with acute ischemic
Thrombolysis for Acute
stroke <6 hours were randomized
Non-interventional Therapy in
to tPA 0.9 mg/kg or placebo
Ischemic Stroke (Stroke 2000;31:811-816)
No significant difference was
seen on any of the planned
efficacy endpoints at 30 and
90 days between groups. The
risk of symptomatic ICH was
increased with rt-PA treatment
particularly in patients treated
between 5 to 6 hours
ATLANTIS B: Alteplase
613 patients with acute ischemic
Thrombolysis for Acute
stroke within 3-5 hours were
Non-interventional Therapy in
randomized to tPA or placebo
Ischemic Stroke (JAMA 1999;282:2019-2026)
No significant difference in
functional recovery at 90 days
between groups. Risk of
symptomatic intracerebral
hemorrhage was increased
in tPA
EMS: Emergency Management
35 patients with acute ischemic
of Stroke Bridging Trial
stroke <3 hours were randomized
(Stroke 1999;30:2598-2605)
to IV plus local intra-arterial (IA)
tPA vs intra-arterial tPA alone
IV/IA treatment resulted in
higher recanalization rate but
no difference in outcome at 7
days or 3 months. The rate of
symptomatic intracerebral
hemorrhage was similar between
groups
ECASS III: European Australasian
821 patients with acute ischemic
Cooperative Acute Stroke Study
stroke within 3 to 4.5 hours were
(N Eng J Med 2008; 359:
randomized to tPA 0.9 mg/kg or
1317-1329)
placebo
Significantly more patients in
the rt-PA treated group had
favorable outcome at 3 months
(52.4% vs 45.2%, p = 0.04). The
incidence of intracranial
hemorrhage was higher with
rt-PA but mortality did not
significantly differ between the
2 groups.
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15
Acute Stroke Treatment
Administration of rt-PA to Acute Ischemic Stroke
Patients (0-3 hours)
1. Eligibility for IV treatment with rt-PA
• Age 18 or older.
• Clinical diagnosis of ischemic stroke causing a
measurable neurological deficit.
• Time of symptom onset well established to be less
than 180 minutes before treatment would begin.
2. Patient Selection: Contraindications and Warnings
• Evidence of intracranial hemorrhage on pretreatment CT.
• Only minor or rapidly improving stroke symptoms.
• Clinical presentation suggestive of subarachnoid
hemorrhage, even with normal CT.
• Active internal bleeding.
• Known bleeding diathesis, including but not limited
to:
♦ Platelet count <100,000/mm
♦ Patient has received heparin within 48 hours and
has an elevated aPTT (greater than upper limit
of normal for laboratory)
♦ Current use of oral anticoagulants (e.g., warfarin sodium) or recent use with an elevated
prothrombin time >15 seconds
• Patient has had major surgery or serious trauma
excluding head trauma in the previous 14 days.
• Within 3 months any intracranial surgery, serious
head trauma, or previous stroke.
• History of gastrointestinal or urinary tract hemorrhage within 21 days.
• Recent arterial puncture at a non-compressible
site.
• Recent lumbar puncture.
• On repeated measurements, systolic blood pressure greater than 185 mm Hg or diastolic blood
pressure greater than 110 mm Hg at the time treatment is to begin, and patient requires aggressive
treatment to reduce blood pressure to within these
limits.
• History of intracranial hemorrhage.
• Abnormal blood glucose (<50 or >400 mg/dL).
• Post myocardial infarction pericarditis.
• Patient was observed to have seizures at the
same time the onset of stroke symptoms were
observed.
• Known arteriovenous malformation, or aneurysm.
3. Treatment
• 0.9 mg/kg (maximum of 90 mg) infused over 60
minutes with 10% of the total dose administered
as an initial intravenous bolus over 1 minute.
4. Sequence of Events
• Draw blood for tests while preparations are made
to perform non-contract CT scan.
• Start recording blood pressure
• Neurological examination.
• CT scan without contrast.
• Determine if CT has evidence of hemorrhage.
• If patient has severe head or neck pain, or is somnolent or stuporous, be sure there is no evidence
of subarachnoid hemorrhage.
• If there is a significant abnormal lucency suggestive
of infarction, reconsider the patient’s history, since
the stroke may have occurred earlier.
• Review required test results — Hematocrit, Plate-
16
•
•
•
•
•
•
•
•
lets, Blood glucose, PT or aPTT (in patients with
recent use of oral anticoagulants or heparin)
Review patient selection criteria
Infuse rt-PA.
Give 0.9 mg/kg, 10% as a bolus, intravenously.
Do not use the cardiac dose.
Do not exceed the 90 mg maximum dose.
Do not give aspirin, heparin or warfarin for 24
hours.
Monitor the patient carefully, especially the blood
pressure. Follow the blood pressure algorithm (see
below and sample orders).
Monitor neurological status.
5. Adjunctive Therapy
• No concomitant heparin, warfarin, or aspirin during
the first 24 hours after symptom onset. If heparin or
any other anticoagulant is indicated after 24 hours,
consider performing a non-contrast CT scan or
other sensitive diagnostic imaging method to rule
out any intracranial hemorrhage before starting an
anticoagulant.
6. Blood Pressure Control
Pretreatment
• Monitor blood pressure every 15 minutes. It should
be below 185/110 mm Hg.
• If over 185/110, BP may be treated with nitroglycerin
paste and/or one or two 10-20 mg doses of labetalol
given IV push or Nicardipine infusion of 5 mg/hour
titrate up by 2.5 mg every 5 - 15 mins interval. If
these measures do not reduce BP below 185/110
and keep it down, the patient should not be treated
with rt-PA.
During and after treatment.
• Monitor blood pressure for the first 24 hours after
starting treatment:
♦ Every 15 minutes for 2 hours after starting the
infusion, then
♦ Every 30 minutes for 6 hours, then
♦ Every hour for 18 hours.
• If systolic BP >230 mm Hg and/or diastolic BP is
121-140 mm Hg, give labetalol 20 mg intravenously
over 1 to 2 minutes. The dose may be repeated
and/or doubled every 10 minutes, up to 150 mg.
Alternatively either an intravenous infusion of 2 to 8
mg/min labetalol may be initiated after the first bolus
of labetalol or Nicardipine infusion 5 mg/hr infusion
is started and titrated up by 2.5 mg/hr every 5 - 15
mins interval until the desired BP is reached.
If satisfactory response is not obtained, use sodium
nitroprusside.
• If systolic BP is 180 to 230 mm Hg and/or diastolic
BP is 105 to 120 mm Hg on two readings 5 to 10
minutes apart, give labetalol 10 mg intravenously
over 1 to 2 minutes. The dose may be repeated
or doubled every 10 to 20 minutes, up to 150 mg.
Alternatively, following the first bolus of labetalol,
an intravenous infusion of 2 to 8 mg/min labetalol
may be initiated and continued until the desired
blood pressure is reached.
• Monitor blood pressure every 15 minutes during
the antihypertensive therapy. Observe for hypotension.
• If, in the clinical judgment of the treating physi-
Acute Stroke Treatment
cian, an intracranial hemorrhage is suspected, the
administration of rt-PA should be discontinued and
an emergency CT scan or other diagnostic imaging
method sensitive for the presence of intracranial
hemorrhage should be obtained.
Management of Intracranial Hemorrhage
• Suspect the occurrence of intracranial hemorrhage
following the start of rt-PA infusion if there is any
acute neurological deterioration, new headache,
acute hypertension, or nausea and vomiting.
• If hemorrhage is suspected then do the following:
♦ Discontinue rt-PA infusion unless other causes
of neurological deterioration are apparent.
♦ Immediate CT scan or other diagnostic imaging
method sensitive for the presence of hemorrhage.
♦ Draw blood for PT, aPTT, platelet count, fibrinogen, and type and cross (may wait to do actual
type and cross).
♦ Prepare for administration of 6 to 8 units of
cryoprecipitate containing factor VIII.
♦ Prepare for administration of 6 to 8 units of
platelets.
• If intracranial hemorrhage is present:
♦ Obtain fibrinogen results.
♦ Consider administering cryoprecipitate or platelets if needed.
♦ Consider alerting and consulting a hematologist
or neurosurgeon.
♦ Consider decision regarding further medical
and/or surgical therapy.
♦ Consider second CT to assess progression of
intracranial hemorrhage.
♦ A plan for access to emergent neurosurgical
consultation is highly recommended.
This Protocol is Based on Research Supported by the National Institute
of Neurological Disorders and Stroke (NINDS) (NOI-NS-02382, N01-NS02374, NO1-NS-02377, NO1-NS-02381, NO1-NS-02379, NOi-NS-02373,
NO1-NS-02378, NOl-NS-02376, NOl-NS-02380).
Expansion of IV rt-PA Treatment Time Window up
to 4.5 Hours
Eligibility for IV treatment follows the same criteria as
treatment within the first 3 hours with the following addi­
tional exclusion criteria:
• Patients older than 80 years old
• Patients on oral anticoagulants, regardless of INR
level
• Patients with NIHSS >25
• Patients with stroke and diabetes
Ancillary care for patients receiving IV rt-PA treatment
at 3 - 4.5 hours after acute ischemic stroke is similar to
that listed above.
Bibiography
1. Adams H, del Zoppo G, Alberts M et aL Guidelines for the early
management of patients with ischemic stroke. 2007 Guidelines update,
a scientific statement from the Stroke Council of the American Heart
Association. Stroke 2007;38:1655- 1711.
2. Del Zoppo, G, Saver J,Juach E and Adams, H on behalf of the American
Heart Association Stroke Council. Expansion of the Time Window for
Treatment of Acute Ischemic Stroke with Tissue Plasminogen Activator, a
science advisory from the American Heart Association / American Stroke
Association. Stroke 2009; 40:2945—2948.
The search for a thrombolytic agent that can be
used beyond the 3 hours of acute ischemic stroke
is being addressed by the ongoing DIAS-3 study or
Desmoteplase In Acute Stroke Study. This double blind
randomized trial will determine whether desmoteplase
is effective and safe in the treatment of patients with
acute ischaemic stroke when given within 3-9 hours
from onset of stroke symptoms. Patients should have
an NIHSS Score of 4-24 and a documented vessel
occlusion or high-grade stenosis on MRI or CTA in
proximal cerebral arteries. The Philippines is participatory in this trial.
BLOOD PRESSURE MANAGEMENT AFTER ACUTE
STROKE
A.BP management in Acute Ischemic Stroke
1. Use the following definitions:
Cerebral Perfusion Pressure (CPP) = MAP-ICP
MAP = 2 (diastolic) + systolic
3
Normal CPP = 70-100 mmHG
Normal ICP = 5-10 mmHG
2. Check if patient is in any condition that may increase
BP such as pain, stress, bladder distention or
constipation, which should be addressed accordingly.
3. Allow “permissive hypertension” during the first
week to ensure adequate CPP but ascertain cardiac
and renal protection.
a. Treat if SBP>220 or DBP>120 or MAP>130
b. Defer emergency BP therapy if MAP is within
110-130 or SBP=185-220 mmHg or DBP=l05120 mmHg, unless in the presence of:
♦ Acute MI
♦ Congestive heart failure
♦ Aortic dissection
♦ Acute pulmonary edema
♦ Acute renal failure
♦ Hypertensive encephalopathy
Rationale for Permissive Hypertension:
• In acute ischemic stroke, autoregulation is
paralyzed in the affected tissues with CBF
passively following MAP. Rapid BP lowering
can lead to further ↓ perfusion in the penumbra.
• HPN is typically present in acute stroke,
with spontaneous decline within the first 5-7
days.
• ↑ ICP during the acute phase of large infarcts
reduces the net CPP.
• Several reports have documented neurological deterioration & poor outcome from rapid
and aggressive pharmacologic lowering of
BP.
4. Use the following locally available intravenous antihypertensives in acute stroke to achieve target MAP
= 110-130 mmHg:
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17
Acute Stroke Treatment
Nicardipine
Drug
Dose
Onset of
Duration Availability/
Stability
Adverse
Action
of Action
DilutionReactions
1-15 mg/hour
5-10 mins 1-4 hours
(10 mg/10 mL 1 to 4 hours Tachycardia,
amp); 10 mg headache,
in 90 mL
flushing
NSS/D5W
dizziness,
somnolence,
nausea
Inhibits calcium
ion from
entering slow
channel,
producing
coronary,
vascular,
smooth muscle relaxation &
vasodilation
Direct vasodilation of arterioles
& decreased
systemic
resistance
5 mg lV push
2-5 mins
2-4 hours
5 mg/mL in
72 hours
Orthostatic
over 2 mins
40 mL vial; hypotension,
repeat with 250 mg in
drowsiness,
incremental 250 mL
dizziness,
dose of 10, 20,
NSS/D5W
lightheaded40, 80 mg until
ness,
desired BP is dyspnea,
achieved or a wheezing,
total dose of & broncho300 mg has
spasm
been adminis-
tered
Alpha- & beta
blocker. Betaadrenergic
blocking activity
is 7x > than
alpha-adrenergic blockers.
Produces dosedependent ↓
in BP without
significant ↓ in
HR or cardiac
output
0.25-0.5 mg/
2-10 mins 10-30 mins 100 mg/
48 hours
Hypotension,
kg IV push 10 mL vial;
bradycardia,
1-2 mins
2500 mg in
AV block,
followed by 250 mL
agitation,
infusion of 0.05 D5W/NSS
confusion,
mg/kg/min
wheezing/
bronchoIf there is no
constriction,
response,
phlebitis
repeat 0.5
mg/kg bolus
dose & ↑ infusion to 0.10 mg/
kg/min. maximum infusion
rate=0.30 mg/
kg/min
Short-acting
beta-adrenergic
blocking agent.
At low doses,
has little effect
on beta 2
receptors
of bronchial &
vascular smooth
muscle
Hydralazine
Tachycardia,
flushing
headache,
vomiting,
increased
angina
Esmolol
Lobetalol
IV push 10-20 10-20 mins 3-8 hours
25 mg/mL
4 days
mg/dose q 4-6
amp; 25
hours as mg/tab
needed, may increase to 40
mg/dose
Action
18
Acute Stroke Treatment
5. Treat patients who are potential candidates for rt-PA
therapy who have persistent elevations In SBP >185
mmHg or DBP >110 mmHg with small doses of IV
antihypertensive agents. Maintain BP just below these
limits.
B.Blood pressure management in Acute Hypertensive ICH
Treat if SBP >180 mmHg or MAP >130 mmHg.
Maintain MAP = 110 or SBP = 160 mmHg
• Absence of ischemic penumbra allows for more
aggressive BP management
• Sustained hypertension may promote early hema­
toma expansion and worse, edema
• Hypotension may result in cerebral hypoperfusion
especially in the setting of increased intracranial
pressure (ICP)
• Two recent phase II clinical trials on BP lowering
namely ATACH and INTERACT has shown that
intensive BP lowering to SBP = 140 in acute ICH is
feasible and is probably safe. Phase III clinical studies are ongoing to determine its clinical efficacy.
Bibliography
1. Adams H, Adams R, del Zoppo G, Goldstein L. Guidelines for the early
management of patients with ischemic stroke. 2005 Guidelines update,
a scientific statement from the Stroke Council of the American Heart
Association. Stroke 2005;36:916-923.
2. Broderick JP, Adams HP, Barsan W, et al. Guidelines for the management
of spontaneous intracerebral hemorrhage: a statement for healthcare
professionals from a special writing group of the Stroke Council of the
American Heart Association. Stroke 1999;30:905-915.
3. Fogelhoim R, Avikainen S and Murros K. Prognostic value and
determinants of first day mean arterial pressure in spontaneous
supratentorial intracerebral hemorrhage. Stroke 1997;28:1396-1400.
4. Guyton A and HaII J. Guyton and Hall’s Textbook of Medical Physiology,
11th ed. USA: WB Saunders; 2005.
5. Kidwell CS, Saver JL, Mattiello J, et al. Diffusion perfusion MR evaluation
of perihematomal injury in hyperacute intracebral hemorrhage. Neurology
2001;57:161 1-1617.
6. Powers WJ, Zazulia AR, Videen TO, et al. Autoregulation of cerebral
blood flow surrounding acute (6-22hours) intracerebral hemorrhage.
Neurology 2001;57:18-24.
7. Qureshi A, Wilson D, Hanley D, Traystman R. No evidence for an
ischemic penumbra in massive experimental intracerebral hemorrhage.
Neurology I 999;52:266-272.
8. Schellinger P, Fiebach J, Hoffman K, et al. Stroke MRI in intracerebral
hemorrhage: is there a perihemorrhagic penumbra? Stroke 2003;34:16471680.
9. The Brain Matters Stroke Initiative. Acute Stroke Management Workshop
Syllabus. Basic Principles of Modern Management for Acute Stroke.
MANAGEMENT OF INCREASED INTRACRANIAL
PRESSURE
A. Signs and symptoms of increased ICP
1. Deteriorating level of sensorium
2. Cushing's triad
i. Hypertension
ii. Bradycardia
iii. Irregular respiration
3. Anisocoria
B. Management options for increased ICP
General:
1. Control agitation and pain with short-acting medications, such as NSAIDS and opioids.
2. Treat fever aggressively. Avoid hyperthermia.
3. Control seizures if present. May treat with phenytoin
with a loading dose of 18-20 mg/kg IV then maintained at 3-5 mg/kg or Levetiracetam 500 mg/IV q 12.
Status epilepticus should be managed accordingly.
4. Strict glucose control between 110-180 mg/dL.
5. Maintain normal fluid and electrolyte balance.
a. Avoid excessive free water or any hypotonic
fluids such as D5W. Potential sources of free
water including hypotonic tube feedings, medications mixed in D5W, nasogastric tube flushes
with water should be minimized.
b. Maintain normal volume status (i.e., 3-3.5 liters
per day in a 60 kg patient).
c. Encourage hyperosmolar state with hypertonic
saline and/or induce free water clearance with
mannitol or diuretics.
6. Use stool softeners to prevent straining.
Specific:
1. Elevate the head at 30 to 45 degrees to assist
venous drainage.
2. Do CSF drainage in the setting of hydrocephalus.
3. Administer osmotic therapy:
• Give Mannitol 20%. Typical doses range from
0.5-1.5 g/kg every 3-6 hours. Doses up to 1.5
g/kg are appropriate when treating a deteriora­
ting patient because of mass effect.
• Hypertonic Saline is an option. It has the advantage of maintaining an effective serum gradient
or rise in osmolality for sustained periods with
lower incidence of intracranial hypertension.
• Always maintain serum osmolality at 300-320
mOsmol/kg
Serum osmolality = 2 (Na) + glucose/18 + BUN/2.8
4. Hyperventilate only in impending herniation by
adjust­ing tidal volume to achieve target PCO2
levels 30-35 mm Hg. Hyperventilation is recommended only for a short term as its effect on CBF
and ICP is short lived ( ≅ 6 hours). Prophylactic
hyperventilation without regard to the level of ICP
and the clinical state should not be done.
5. Carefully intubate patients with respiratory failure
defined as SpO2 of less than 90% by pulse oximeter
and PaO2 <60 mmHg, and/or PaCO2 >55 mmHg
by arterial blood gas analysis.
6. Consider surgical evacuation or decompressive
hemicraniectomy if indicated.
7. ICP catheter insertion is useful for the diagnosis,
monitoring and therapeutic lowering of increased
ICP. It is recommended in patients with a GCS ≤8,
those with significant IVH or hydrocephalus. CPP
should be maintained at 60-70 mmHg.
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19
Acute Stroke Treatment
C. Sedatives and Narcotics available locally
Drugs
Usual Dose
Onset of
Action
Duration
Comments
of Effect
Availablity/ Duration
Midazolam 0.025-0.35
1 to 5 min
2 hours
Unpredictable sedation
mg/kg
Diazepam 0.1-0.2 mg/kg
Immediate
20 to 30
Sedation can be reversed
minutes
with flumazenil (0.2-1 mg
at 0.2 mg/min at 20 min
interval, max dose 3 mg
in one hour)
Propofol
5-50 ug/kg/min
<40 secs
10 to 15 min
Expensive
Ketorolac
50-100 mg 1V
1 hour
6 to 8 hours
NSAID
Tramadol
50-100 mg 1V
1 hour
9 hours
Centrally acting synthetic
analgesic compound not
chemically related to
opiates but thought to bind
to opioid receptors and inhibit
reuptake of NE and serotonin
Fentanyl
50-100 ug/hour
1-2 mins
>60 min
Can be easily reversed
with naloxone (0.4-2 mg IVP;
repeat at 2-3 min intervals,
max dose 10 mg) * 110x more
potent than morphine
Morphine
2-5 mg/hour
5 mins
>60 min
Opioid
Dexme1 mcg/kg/hr LD
30-60 secs
3-5 mins
detomidine for 10 mins then
(Precedex) maintenance
dosing at 0.4 mcg/
kg/hr (Dose range:
0.2-0.7 mcg/hr)
Items
I. Glasgow Coma Scale
Eye Opening
Spontaneous
To speech
To pain
None
Best Motor Response
Obeys
Localizes
Withdraws
Abnormal flexion
(decorticate)
Abnormal extension
(decerebrate)
None
Best Verbal Response
Oriented
Confused
Inappropriate words
Incomprehensible sounds
None
20
(10 mg/mL)
100 mL vial
(premixed)
30 mg/mL amp
50 mg/ 2 mL amp;
100 mg/2 mL amp
100 ug/2 mL;
2,500 ug in 250 mL
NSS/D5W
10 mg/mL gr 1/6;
16 mg/mL gr 1/4
200 mcg/2 mL vial
II. National Institutes of Health (NIH) Stroke Scale
STROKE SCALES
Category
15 mg/3 mL amp;
5 mg/5 mL amp;
50 mg in 100 mL
NSS/D5W
10 mg/2 mL amp;
50 mg in 250 mL
NSS/D5W
Score
4
3
2
1
6
5
4
3
2
1
5
4
3
2
1
Scale Definition
Ia. Level of
0 = Alert, keenly responsive
Consciousness 1 = Not alert, but arousable by
(LOC)
minor stimulation to obey, answer
or respond
2 = Not alert, requires repeated
stimulation to attend, or is obtunded and requires strong or painful
stimulation to make movements
(not stereotyped)
3 = Responds only with reflex motor or autonomic effects or totally
unresponsive, flaccid, areflexic
Ib. LOC Questions 0 = Answers to both questions
correctly
1 = Answers one question correctly
2 = Answers neither question correctly
Ic. LOC
0 = Performs both tasks correctly
Commands
1 = Performs one task correctly
2 = Performs neither task correctly
2. Best gaze
0 = Normal
1 = Partial gaze palsy. Gaze is
abnormal in one or both eyes
but forced deviation or total gaze
paresis is not present.
2 = Forced deviation, or total gaze
paresis is not overcome by oculocephalic maneuver
3. Visual
0 = No visual loss
1 = Partial hemianopia
2 = Complete hemianopia
Acute Stroke Treatment
Items
4. Facial palsy
5. Motor (Arm)
5a. Leftarm
5b. Right arm
6. Motor (Leg)
6a. Right leg
6b. Left leg
Scale Definition
3 = Bilateral hemianopia (blind,
including cortical blindness)
0 = Normal symmetrical movement
1 = Minor paralysis (flattened nasolabial fold, asymmetry on smiling)
0 = No drift; limb holds 90 (or 45)
degrees for full 10 seconds
1 = Drifts; limb holds 90 (or 45)
degrees but drifts down before
full 10 seconds; does not hit bed
or other support
2 = Some effort against gravity,
limb cannot get up to or maintain
(if cued) 90 (or 45) degrees; drifts
down to bed, but has some effort
against gravity
3 = No effort against gravity, limb falls
4 = No movement
9 = Amputation or joint fusion; explain
0 = No drift; leg holds 30-degree
position for full 5 seconds
1 = Drifts; leg falls by the end of the 5second period but does not hit bed
2 = Some effort against gravity,
leg falls to bed by 5 seconds but
has some effort against gravity
3 = No effort against gravity, leg
falls to bed immediately
4 = No movement
9 = Amputation or joint fission; explain
7. Limb ataxia
0 = absent
1 = Present in one limb
2 = Present in two limbs
9 = Amputation or joint fusion; explain
8. Sensory
0 = Normal; no sensory loss
1 = Mild to moderate sensory loss;
patient feels pinprick is less sharp
or dull on the affected side; or
there is a loss of superficial pain
with pinprick, but patient is aware
he/she is being touched
2 = Severe or total sensory loss;
patient is not aware of being
touched in the face, arm or leg
9. Best Language 0 = No aphasia
(Fig. 1)
1 = Mild to moderate aphasia; some
obvious loss of fluency or facility
of comprehension, without significant limitation on ideas expressed
or form of expression. Reduction
of speech and/or comprehension,
however, makes conversation
on provided material difficult.
2 = Severe aphasia; all communication is through fragmentary expression; great need for inference,
questioning and guessing by the
listener. Range of information that
can be exchanged is limited; listener
carries the burden of communication
3 = Mute, global aphasia; no usa­ble
speech or auditory comprehension
10. Dysarthia
0 = Normal
(Fig. 2)
1 = Mild to moderate; patient slurs at
least some words and at worst, can
be understood with some difficulty
2 = Severe; patient’s speech is so
slurred as to be unintelligible in the
absence of or out of proportion to
Items
11. Extinction &
Inattention
Scale Definition
any dysphasia, or is mute/anarthric
9 = intubated or other physical
barrier; explain
0 = No abnormality
1 = Visual, tactile, auditory, spatial
or personal inattention or extinct­ion
to bilateral simultaneous stimulation in one of the sensory modalities
2 = Profound hemi-attention or hemiinattention to more than one modality. Does not recognize own hand or
orients to only one side of space.
*Total score = 42
Fig. 1: Aphasia
Ask the patient to describe what is happening on the
picture and name items.
Fig. 2: Dysarthria
Ask the patient to read or repeat words from the list.
MAMA
TIP-TOP
FIFTY-FIFTY
THANKS
HUCKLEBERRY
BASEBALL PLAYER
III. Modified Rankin Scale
No symptoms at all
No significant disability despite
symptoms; able to carry out all usual
duties and activities
Slight disability; unable to carry out all
previous activities but able to look after
own affairs without assistance
Moderate disability; requiring some
help but able to walk without assistance
Moderately severe disability; unable to
walk without assistance and unable to attend
to own bodily needs without assistance
Severe disability; bedridden, incontinent and
requiring constant nursing care and attention
Death
Score
0
1
2
3
4
5
6
Bibliography
1. Brott T, Adams H, Olinger CP, et al. Measurements of acute cerebral
infarction: a clinical examination scale. Stroke 1989;20:864-870.
2. Goldstein LB, Bartels C. Davis JN. Interrater reliability of the NIH Stroke
Scale. Arch Neurol 1989;46:660-662,
3. Rankin J. Cerebral vascular accidents in patients over the age of 60.
Scot Med J 1957;2:200- 215.
4. Van Swieten JC, Koudstaal JP, Visser MC, et al. Interobserver agreement
for the assessment of handicap in stroke patients. Stroke 1988;19:604-607.
5. The Brain Matters Stroke Initiative. Acute Stroke Management Workshop
Syllabus. Basic Principles of Modern Management for Acute Stroke.
www.TheFilipinoDoctor.com l Sign up and open your clinic to the world.
21
Acute Stroke Treatment
Recommended Therapeutics
The following index lists therapeutic classifications as recommended by the treatment guideline. For the prescriber's
reference, available drugs are listed under each therapeutic class. For drug information, please refer to the Philippine
Drug Directory System (PPD, PPD Pocket Version, PPD Text, PPD Tabs).
Anticoagulants
Citilin
Nicholin
Somazine
Heparin Sodium
Heparin Leo
Zynohep
Hypnotic /Sedative
Antiplatelets
Benzodiazepines
Aspirin
Aspen
Aspilets
Aspilets-EC
Bayer Aspirin 100 mg
Bayprin EC
Cor-30
Drugmaker's Biotech
Aspirin
Rhea Aspirin
Tromcor
Aspirin/Dipyridamole
Aggrenox
Cilostazol
Ciletin
Clazol
Dancitaz
Pletaal
Trombocil
Clopidogrel
Clopimet
Declot
Klopide
Plavix
Plogrel
Winthrop Clopidogrel
Vivelon
Clopidogrel bisulfate
Cardogrel
Clopida
Clopido
Clotiz
Deplatt
Noklot
Norplat
Thromvix
Clopidogrel hydrogen sulfate
Clopivaz
Dipyridamole
Drugmaker's Biotech
Dipyridamole
Persantin
Ticlopidine HCl
Clotidone
Diazepam
Trankil
Valium
Midazolam
Dormicum
Sedoz
Calcium Antagonist
Nicardipine HCl
Cardepine
Vasodilators
Hydralazine HCl
Apresoline
CNS Stimulants/Neurotonics
Citicholine
Brainact
Cholinerv
22
General Anesthetics
Parenteral
Propofol
Diprivan
Fresofol 1%
IV-Pro
Analgesic/Antipyretics & Muscle
Relaxants
NSAIDS
Ketorolac
Acular
Ketanov
Ketodol
Ketomed
Kortezor
Remopain
Toradol
Xevolac
Opiates & Antagonist
Fentanyl
Durogesic D Trans
Sublimaze
Morphine
Hizon Morphine Sulfate
MST Continus
Tramadol
Dolmal
Dolotral
Gesidol
Milador
Milador Inj
Radol
Relidol
Siverol
TDL
Tolma
Tradonal
Tramal
Tramid
Tramundin
Vistra
Vitral
Tramadol/Paracetamol
Algesia
Cetra
Dolcet