Intracerebral

Hemorrhage (ICH)
Krishna Nalleballe MD
 Acute Management of ICH
• Predicting hematoma expansion

• Preventing hematoma expansion

• Blood pressure control
• Reversing INR
• Platelet transfusion?
• Metabolic

• Monitoring for complications of ICH

• Seizures
• Hydrocephalus
 Is it expanding?

0-3 3-6 6-12 12-24 24-48

hours from onset

Stroke 1996;27:1783-87
 Spot sign

Wada et al., 2007

 Calculating ICH volume
AxBxC

2
• Select CT slice with largest ICH
• A = longest axis (cm)
• B = longest axis perpendicular to A (cm)
• C = number of slices x slice thickness (cm)
 ICH score
ICH volume Score 30-day mortality
> 30cc 1 0 0%
< 30cc 0
Intraventricular extension 1 13
Yes 1 2 26
No 0 3 72
Infratentorial location
4 97
Yes 1
No 0 5, 6 100
Age
> 80 1
< 80 0
Glasgow coma scale
3-4 2
5-12 1
13-15 0
Total score 0-6

Godoy, D. A. et al. Stroke 2006

Impact of intraventricular blood

ICH =80 cc, GCS 8

_____
……..
ICH =80 cc, GCS >8
__ __
ICH =20 cc, GCS 8
----- ICH =20 cc, GCS >8

Tuhrim et al. Crit Care

Med 1999;27:617-21
 Preventing hematoma expansion
• Blood pressure control
• Reversing INR
• ? Platelet transfusion
• Metabolic
 Preventing Hematoma Expansion
• Blood Pressure Control
Target blood pressure 140 systolic?
INTERACT 2 trial

• Patients within 6 hours of onset of ICH

• Treatment arm: SBP <140

• Control arm: SBP <180

 INTERACT 2: results
Intensive group to target (<140mmHg) Systolic BP time trends
462 (33%) at 1 hour 1 hour - Δ14 mmHg (P<0.0001)
731 (53%) at 6 hours 6 hour - Δ14 mmHg (P<0.0001)
200

190 Standard
Intensive
Mean Systolic Blood Pressure (mm Hg) 180

170
164
160
153
150 150

140
Target level 139
130

120

110 P<0.0001
beyond 15mins
0 // //
am pm am pm am pm am pm am pm am pm
R 15 30 45 60 6 12 18 24 2 3 4 5 6 7
Minutes Hours Days / Time
 INTERACT 2: results
• No difference between groups in death or major disability

• Intensive blood pressure lowering resulted in better functional outcomes at

90 days than standard therapy
 BP Control
• AHA Statement:
• For ICH patients presenting with SBP between 150-220 mm Hg and with
out contraindication to acute BP treatment, lowering of SBP to 140 mm Hg
is safe (class1; Level of Evidence A) and can be effective for improving
functional out come (class 2a; Level of Evidence B)
• For ICH patients presenting with SBP>220 mm Hg, it may be reasonable to
consider aggressive reduction of BP with a continuous intravenous infusion
and frequent BP monitoring (class 2a; Level of Evidence C)
 Preventing Hematoma Expansion
• Reversing Anticoagulation
 Reversing the INR
• No more fresh frozen plasma
• Choose prothrombin complex concentrate
• Kcentra
• Vitamin K dependent coagulation factors II, VII, IX, X and protein C+S
• Give vitamin K IV along with it
 Kcentra vs. FFP
• Patients with INR ≥ 2 requiring reversal of INR for an acute major bleeding
event
• Primary endpoints:
• Hemostatic efficacy within 24 hours of the infusion (excellent, good, poor, none)

• INR half hour after the infusion

 Results
• Effective hemostasis in 72.4% of the 4-factor PCC group vs. 65.4% of the
FFP group
• PCC non-inferior to FFP

• INR ≤ 1.3 at half an hour after the end of the infusion in 62.2% of the PCC
group vs. 9.6% of the FFP group
• PCC superior to FFP
 Adverse events
• Kcentra
• ischemic stroke
• DVT

• FFP
• 2 MIs
• fluid overload
• respiratory failure
 Advantages of PCC
• Less volume
• Rapid reversal of the INR to less than 1.3 within 30 minutes
• Rapid infusion rate – 8.4 mL/minute
 Kcentra dose

Usually 25 units/ mL
Therefore 3500 units = 140 mL

FFP would have been 1050 mL (15mL/kg)

 Reversal
• AHA Statement:
• Patients with ICH whose INR is elevated because of VKA should have their
VKA withheld, receive therapy to replace vitamin K-dependent factors and
correct the INR and receive intravenous vitamin K (class 1; Level of
Evidence C).
• PCCs may have fewer complications and correct the INR more rapidly than
FFP and might be considered over FFP (class 2b; Level of Evidence B)
• rF7a does not replace all clotting factors and so is not recommended
 NOAC
• AHA Statement:
• For patients with ICH who are taking dabigatran, rivaroxaban, or apixaban,
treatment with FEIBA, other PCCs, or rF7a might be considered on an
individual basis. Activated charcoal might be used if most recent dose was
taken <2 hours earlier.
• FEIBA is anti-inhibitor coagulant complex used approved for hemophilia
• Praxbind is Idarucizumab is humanized monoclonal ab , 5g IV (2 doses of
2.5gms, no more than 15 mins apart)
 Heparin
• AHA Statement:
• Protamine Sulfate may be considered to reverse heparin in patients with
acute ICH (Class2b; Level of Evidence C)
 AHA guidelines: ICH on heparin

• Protamine sulfate 1mg per 100 units heparin

• Dose decreases depending on time since IV heparin was stopped

• 30-60 min: 0.5-0.75 mg/100 units heparin
• 60-120 min: 0.375-0.5 mg/100 units heparin
• >120 min: 0.25 mg/100 units heparin

• Slow IV infusion, max rate 5 mg/min (high risk of severe hypotension if

faster)
 Preventing Hematoma Expansion
• Platelet Transfusion
 Platelet transfusion for ASA use?

• 282 ICH cases imaged at onset and at 72 hours, including 70 (25%) taking antiplatelet
medication
• No difference in baseline hematoma volume
• No difference in hematoma growth at 72 hours
• No difference in need for surgical evacuation
• No difference in Rankin score at 90 days
• No difference in mortality
 Platelet Transfusion
• AHA Statement:
• The usefulness of platelet transfusions in ICH patients with a history of
antiplatelet use is uncertain (class 2b: Level of Evidence C)
• Patients with a severe coagulation factor deficiency or severe
thrombocytopenia should receive appropriate factor replacement therapy or
platelets, respectively (class 1; Level of Evidence C)
 Factor VII for acute ICH

• Used for hemophiliacs with Factor VIII antibodies

• FAST Trial
• Phase 3 trial of Factor VII for acute ICH (not on warfarin)
• Primary outcome: severe disability or death at 90 days
• 821 patients randomized to placebo, 20, or 80 mcg/kg
• Treatment started within 4 hours of onset

NEJM 2008;358:2127-2137
 Factor VII reduced ICH growth

• Reduced ICH growth with 80 0

mcg/kg vs placebo -1
Hematoma
volume
• Time mattered: earlier treatment => -2
(ml) vs
placebo
less growth -3

-4

-5

-6
<2 hours <3 hours <4 hours
 90 day death/severe disability

• No clinical benefit
• MI and ischemic stroke
absolute risk increased 5%
 Factor 7
• AHA Statement:
• Although rfactor7a can limit the extent of hematoma expansion in
noncoagulopathic ICH patients, there is an increase in thromboembolic risk
with rF7a and no clear clinical benefit in unselected patients. This rF7a is not
recommended (class 3; Level of Evidence A)
 Preventing Hematoma Expansion
• Metabolic
 Metabolic
• Glucose should be monitored. Both hyperglycemia and hypoglycemia should
be avoided (class 1; Level C)
• Treatment of fever after ICH may be reasonable (class 2b; Level C)
• Systemic screening for MI with ECG and cardiac enzyme testing after ICH is
reasonable (class 2a; Level C)
• A formal dysphagia screen should be performed in all patients before
initiating oral intake to reduce pneumonia risk (class 1; Level B)
 Complications of ICH
• Seizures
• Hydrocephalus
• DVT/PE
 Seizures
• Prophylactic antiseizure medication is not recommended (class 3; Level B)
• Clinical Seizures should be treated with antiseizure meds (Class 1;Level A)
• Continuous EEG monitoring is probably indicated in ICH patients with
depressed mental status that’s out of proportion to degree of brain injury
(Class 2a; Level C) and should be treated with antiseizure meds if found to
have electrographic seizures on EEG (class 1; Level C)
Hydrocephalus
 Clinical manifestations of Hydrocephalus
• Headache
• Vomiting
• Drowsiness → Coma
 Indications for EVD
• EVD as treatment for hydrocephalus is reasonable, esp. in patients with
decreased level of consciousness (class 2a; Level B)
 Steroids for ICH: NO!!!

• Single-center, double-blind randomized trial

• Dexamethasone versus placebo within 48 hours of onset for 9
days total
• Trial halted after enrollment of 93 patients due to high rate of
complications and no clinical benefit

NEJM 1987;316:1229-1233
 DVT
• Risk of DVT in hemiplegic patients is 10-50% during acute hospitalization

• Intermittent pneumatic compression must be used immediately (class 1; Level A)

• Graduated compression stockings are not beneficial to reduce DVT or improve out
comes (class 3; Level A)

• After 1-4 days from onset LMW heparin or unfractionated heparin.

 Intraventricular Hemorrhage
• Although intraventricular administration of rtPA in IVH appears to have a
fairly low complication rate, the efficacy and safety of this treatment are
uncertain (class 2b; Level B)
• The efficacy of endoscopic treatment of IVH is uncertain (class 2b; Level B)
 STICH Trial
• Multicenter international randomized trial of early surgery versus medical
management for ICH
• Crossover to surgery possible, so NOT strictly a trial of surgery versus medicine
• Surgeon uncertain about benefit of surgery
• Randomization within 72 hours of ICH; surgery within 24 hours of randomization
• Supratentorial ICH only

• 1033 patients randomized

Mendelow et al. Lancet 2005

STICH Results
 Surgery
• Patients with cerebellar hemorrhage who are deteriorating neurologically or
have brain stem compression or hydrocephalus should under go surgical
removal as soon as possible (class 1; Level C)
• Initial treatment of these patients with ventricular drainage rather than
surgical evacuation is not recommended (class 3; Level C)
• For most patients with supratentorial ICH, usefulness of surgery is not well
established (class2b; Level A)
 Surgery
• Policy of early hematoma evacuation is not clearly beneficial compared to
hematoma evacuation when patient deteriorates (Class 2b; Level A)
 Deep ICH is like lacunar infarct
• Deep ICH occurs in:
• Basal ganglia and thalamus
• Pons
• Cerebellum

• Pathology is similar to lacunar infarct

• Lipohyalinosis
• Charcot-Bouchard aneurysms—may be artifactual

• After deep ICH, annual risk of recurrence is: 2.1%

Neurology 2001;56:773-777
 Cerebral amyloid angiopathy
• The most common risk factor for lobar ICH
• Infiltration of cortical vessels by amyloid protein
• Probable CAA: age>55with recurrent lobar ICH
• After a first lobar ICH, the 2-year cumulative incidence of a second ICH
is…

21%
N Engl J Med 2000;342:240-245
CAA-Boston Diagnostic
Criteria
ICH 30-Day Mortality: 30-50%
 Restarting AC
• Avoidance of long term AC as treatment for nonvalvular afib is probably
recommended after AC associated spontaneous lobar ICH due to relatively
high risk of recurrence (class 2a; Level B)
• AC after nonlobar ICH and antiplatelet therapy after an ICH might be
considered, particularly when there is strong indication (class 2b; Level B)
• Optimal timing to resume AC after ICH is uncertain. Avoidance of AC for at
least 4 weeks in patients in patients with out mechanical valves, might
decrease ICH recurrence (class 2b; Level B)
 References
• Anderson et al. Rapid blood pressure lowering in patients with acute intracerebral hemorrhage.
NEJM. 2013; 368: 2355-65.
• Kazui et al. Enlargement of spontaneous intracerebral hemorrhage. Stroke. 1996; 27(10): 1783-
87.
• Morgenstern et al. Guidelines for the management of spontaneous intracerebral hemorrhage.
Stroke. 2010; 41: 2108-2129.
• Sarode et al. Efficacy and safety of a 4-factor PCC in patients on vitamin K antagonists
presenting with major bleeding. Circulation. 2013; 128: 1234-43.
• Wada et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral
hemorrhage. Stroke. 2007; 38:1257-62.