Reference : Dastur CK, Yu W. Current management of spontaneous intracerebral haemorrhage. Stroke and Vascular Neurology 2017;00: e000047. doi:10.1136/svn- 2016-000047

1. Update in ICH
management
Stroke unit
3 FEB 2018 Woralux P, MD

2. Reference
Dastur CK, Yu W. Current management of spontaneous intracerebral haemorrhage.
Stroke and Vascular Neurology 2017;00: e000047. doi:10.1136/svn- 2016-000047
Power point presentation and Short note
Woralux phusoongner, MD.

3. Current management of Spontaneous
Intracerebral haemorrhage
Dastur CK, Yu W. Current management of spontaneous ICH.
Stroke and Vascular Neurology 2017 00: e000047. doi:10.1136/svn-
2016-000047

4. Spontaneous ICH and HT
Uncontrolled Hypertension is the
most common risk factor for
Spontaneous ICH
Limited in Primary care
Anti HT medication - Incidence of ICH is higher in
Asian.
- 62.8 million disability-associated
life years were lost compare to
39.4 million in ischemic stroke
Caring for patient with ICH involved with
1. Intensive care team 2. Medical 3. Surgical team
This review will summarise the advances in evaluation
and management of ICH.

5. Classification
1. Primary ICH
- 70 to 80 % of curses
- Cause : Spontaneous rupture of small vessels damage by HT
or amyloid antipathy
- Classified : Lobar/Non-lobar or Supratentorial/infratentorial
2. Secondary IC
- Congential
- Acquired : AVM, Tumours, Coagulation disorders, use of
anticoagulants and Thrombolytic agents , Cerebral
vasculitis, Drug abuse and Cerebral venous thrombosis
Spontaneous ICH

6. Primary ICH
1. Locar ICH
- Commonly result for Cerebral amyloid antipathy ( CAA )
- Etiology : Amyloid deposition in small-sized to medium sized
cortical perforators that may lead to rupture of these vessel
- Result : 1. Asymptomatic microhemorrhage or 2.
Symptomatic lobar haemorrhage
2. Non-lobar ICH
- Long-standing high blood pressure
- Etiology : Lipohyalinosis of small perforateng arteries of
Basal ganglia, Thalamus, pons and cerebellum
- Result : deep haemorrhage, often with extension into the
ventricles

7. Common site of Hypertensive ICH
1. Putamen
2. Thalamus
3. Subcortical white matter
4. Pons
5. Cerebellum
Thalamic and subcritical haemorrhage often extend into the Ventricle ( B,C )
CAA , drug abuse or vascular anomaly often causes lobar haemorrhage (F)

8. Diagnosis
1. History
- Severe headache, Vomiting , Rasing of BP, Decrease level of
consciousness
- * Early Dx is Crucial for management *
- * Early worsening of clinical in few hour after onset is
common from (1) hematoma expansion and from (2)
Secondary injury
2. V/S and Physical examination: Location ?
History and Physical examination

9. Diagnosis
1. CT brain non contrast
- High sensitivity and Specificity
- Location / Size / Mass effect / Hydrocephalus / Herniation
sign
- Hematoma volume *
2. MRI brain
- Rarely role in acute setting
- Delayed MRI is better to determine the underlying cause
(Tumour , Cavernoma , CAA )
3. CT angiogram
- Vascular abnormality **
Imaging

10. Imaging
- ABC/2 method
- A= maximal hematoma diameter on axial slice with
largest area
- B = perpendicular to A ( maximal hematoma diameter)
- C = number of CT with hematoma multiplied by slice
thickness ( ignoring slice with < 25% of hematoma
area compared with the reference spice)
Hematoma volume*

11. Imaging
- Contrast extravasation during angiogram
- “Spot sign” = contrast extravasation
- “Leakage sign”=
- Higher sens and spec for hematoma expansion
than spot sign
- Association with poor outcome
- Risk of contrast leakage
- Extreme HT
- Depressed consciousness
- Large haemorrhage
CT Angiogram **

12. Management

13. More than 20% of patients have decrease GCS after
initial assessment by EMS
15-23% have hematoma expansion and
Neurological decline in the first several hours

14. ED Algorithm for early diagnosis and emergent interventions.

15. Management
- Emergent intervention
- Airway, Breathing , Circulation
- Prevent form Hypoxia, HTN , Hematoma expansion
- Intubation for airway protection , GCS < 8 or RS
distress
- Mannitol 0.5-1 g/kg or Hypertonic saline when?
- Decrease level of conscious form IVH,
Hydrocephaluss , Mass effect or brain stem
herniation
Emergent intervention

16. Management of HT
- Two large phase III, Multicentre, Prospective RCT
- Early lowering SBP to < 140 mmHg is safe without
significant adversary effects
- INTERACT-2 trial
- Comparing early lowering of SBP to < 140 mmHg with
< 180 mmHg
- No increase in adverse event in the aggressive
treatment group
- No significant difference in death or severe disability at
90 days
- An Ordinal analysis of modified Rankin score indicated
improved functional outcomes with intensive lowering
the BP.
Review studies

17. Management of HT
- ATACH II ( the antihypertensive treatment of acute
cerebral haemorrhage )
- Used IV Nicardipine within 3 hours of ICH onset to
target SBP < 140 mmHg VS SBP < 180 mmHg
- No significant different in the primary end points of
death or diability at 90 days
- Higher incidence of Adverse renal event in intenseive
treatment than standard group ( 9.0% vs 4.0 % ,
p=0.002 )
Review studies

18. Management of HT
- ATACH II ( the antihypertensive treatment of acute
cerebral haemorrhage )
- The mean minimum SBP of the two group during the
first 2 hour were 128.9 + 16 and 141.1 + 14.8 mmHg
Compare to INTERACT-2Trial study
*The mean minimum BP in the ATACH II much lower than
150 and 164 mmHg
*The much lower minimum SBP in the Intensive treatment in
ATACH II might explain the higher incidence of Adverse
renal events.
Review studies

19. Management of HT
- AHA/ASA Guideline for Management of
Spontaneous ICH 2015
- Recommend for SBP 150 -200 mmHG, Acute lowering
of SBP to 140 mmHg is safe and may be effective for
improving the functional outcome
- The optimum target for patient presenting with SBP >
220 mmHg is less clear
- Follow up clinical and monitoring
Review studies

20. Management of HT
- IV Calcium channel blockers ( eg. Nicardipine ) and
B-blocker ( eg. Labetalol )
- Treatment of choice for early BP reduction ( Short half
life and ease of titration)
- Oral anti HT should be started as soon as possible
- A-ine is recommend to optimise BP monitoring and
medication titration
- * Nitrate should be avoid ( cause vasodilation and
increase ICP )
Medication choices

21. Management of HT
- Resistant HTN
- ACE-1, ARB and CCB
- First-line and second-liked drug for resistant
patients
- 3th and 4th line are varies.
- Thiazide-like diuretic at maximal tolerated dosed as an
optimal triplets formula
- Hyponatremia and cause cerebral edema
- Spironolactone and Alpha-/Beta antigenist
- Effective for resistant HTN in recent study
- Can be used as the 3rd and 4th agent to
maintain BP while weening the IV agent
Medication choices

22. Management of HT
- Resistant HTN
- During acute phase, patients may have resistant HTN
due to sympathetic surge
- A few weeks later, they may required fewer
medications and be at risk for hypotension unless the
doses of medication are adjusted promptly
Medication choices

23. Reversal of Coagulopathy
- Coagulopathy , whether medication-induced or systemic
disease is associated with hematoma expansion
- 12-20% of patients presenting with ICH are taking oral
anticoagulants
- The acute reversal of coagulopathy has not been clearly
shown to beneficial in large RCT.
Review studies

24. Reversal of Coagulopathy
- Neurocritical Care society, Guideline for reversal
of Antithrombotic agent in patients with ICH,
December 2015
- The method of reversal will depend on the agent used
Review studies

25. Reversal of
Drug reversal :
1. Vitamin K 10 mg
2. 3-factor or 4-factor prothrombin complex concentrates
( PCCs )
Indication :
1. IV route for patient with INR > 1.4
Repeat INR 15-60 min after PCC administration shows
continue INR elevation above 1.4, Consider
Fourther correct with 2-4 unit FFP
Vitamin K antagonists
Wafarin

26. What is
Prothrombin complex concentrates ( PCCs )
- Inactivated concentrate of factors II, IX and X with variable
amounts of factors VII ( the variation in Factor VII led to
classification of 3- and 4- factors )
- Lyophilized and can be reconstituted quickly for timely
administration
- The concentration of Vitamin K-dependent clotting factor is
about 25 times higher than plasma and can reviser
coagulopathy quickly.
PCCs ? And Compare with others

27. What is
Prothrombin complex concentrates ( PCCs )
- PCC is proffered over FFP due to more rapid correction of INR
- Lower volume and risk of infection
- Lower pulmonary edema, Transfusion-Related Acute lung
injury ( TRALI ) and Transfusion associated cardiac
overload ( TACO)
PCCs ? And Compare with others

28. What is
- Associated with relatively high thrombosis rated
- Only considered in patients who will not accept blood
products ( eg. Jehovah’s witness)
rFVIIa ( Recombinant factor VIIa )

29. What is
- eg. : Dabigatran, Argatroban, Bivalirudin
- Significantly less risk of ICH than Vitamin K antagonist
- However, Haemorrhage do occur and reversal of
coagulopathy is indicated if patient presents within 3-5 half-
lives of drug exposure ( or beyond renal insufficiently )
Direct thrombin inhibitors ( DTIs )
Direct thrombin inhibitors ( DTIs )

30. Idarucizumab ( 5 g IV divided into two doses)
- Specific neutralising monoclonal antibody fragment for
Dabigatran
- Recommend in case of haemorrhage associated with
Dabigatran
If it is not available or if haemorrhage is associated with DTI
other than dabigatran
- 4 factor PCC ( 5 u/kg ) or activated PCC ( 50 u/kg ) is
recmmoended.
- Hemodialysis can also be considered in patients with
dabigatran-associated ICH and Renal insufficiency ,
especially if continued haemorrhage despite first line
treatment
Direct thrombin inhibitors ( DTIs )

31. The Guidelines for reserving Wafarin and Novel oral anticoagulants
( NOAC ) coagulopathies in patients with symptomatic ICH

32. What is
- eg. : Rivaroxaban , Apixaban , Edoxaban
- 4-factor PCC ( 50 units/kg) or Activated PCC ( 50 units/kg ) is
recommended if the haemorrhage occurred within 3-5 half
lives of drug exposure ( or in liver failure )
- If presenting within 2 hour, Activated charcoal can be used to
prevent further drug absorption.
No lab test to Guide the treatment !!
The reversal should be guided by Bleeding ( major or
intracranialal )
Factor Xa inhibitors
Factor Xa inhibitors

33. What is
- Andexanet alfa : recombinant modified factor Xa that can
bind and reserve oral and parenteral factor Xa inhibitors
- Including : rivaroxaban, Apixaban and Edoxaban, and
LMWH
- Not approved by FDA for clinical use
Factor Xa inhibitors
Andexanet alfa

34. Reversal of
Drug :
IV Protamine ( 1 mg per every 100 unit of heparin give in past
2-3 hours , Max 50 mg )
And repeated at half of the initial dose if repeat aPTT remains
elevated.
Unfractionated heparin
Indication :
Patient who develop ICH while on heparin infusion
Reversal of prophylactic SC heparin should only be considered if
aPTT is significantly prolonged in setting of new haemorrhage
Heparin

35. Reversal of
Drug :
For Enoxaparin administered within past 8 hours,
1 mg of protamine / every 1 mg of Enoxaparin
If given 8 -12 hour
0.5 mg of protamine / every 1 mg of Enoxaparin
LMWH
Enoxaparin, Dalteparin, Nadroparin an Tinzaparin
Indication :
Recommended only if receiving therapeutic doses
Enoxaparin

36. Reversal of
Drug :
1 mg / every 100 anti-Xa unit of LMWH, up to maximum 50 mg
This can be repeated at half of the initial dose if continue
bleeding or patient has renal insufficiency
LMWH
In case of Dalteparin, Nadroparin and Tinzaparin
rFVIIa is generally not recommend, but can be
consider if protamine contraindicated.

37. Reversal of
Drug :
10 units of Cryoprecipitate may be considered
If the level of fibrinogen is < 150 mg/dL post cryoprecipitate use
, consider additional cryoprecipitate administration
If Cryoprecipitate is contraindicated or unavailable,
Tranexamic acid ( 10 -15 mg/kg IV or Gramma Aminocaproic
acid 4-5 g IV )
rTPA ( thrombolytic )
rTPA

38. Drug :
- Platelet transfusion is no recommended routinely
* Some study
1. In multicenter in 60 hospital in UK, France, Netherland 190
patients, in ICH on anti platelet for at least 7 days prior to ICH will
be given the platelet transfusion.
2. Platelet transfusion should be considered for patient that ICH with
on ASA who will undergo a neurosurgical procedure.
( platelet function test : TT if it is normal or anti platelet resistance
the platelet transfusion should be avoided )
3. Platelet transfusion is no recommend for NSAID or GP IIb/IIa
related ICH
- ddAVP 0.4 microgram / kg IV once. Can be considered in ICH
associated with COX inhibitors or ADP receptor
Aspirin , Clopidogrel and Abciximab

39. Management of IVH and Hydrocephalus
•IVH occurs in up to 45% of patients with ICH
•Associated with Lower GCS ( predictor of poor outcome )
Considered
1. GCS < 8
2. Significant IVH
3. Hydrocephalus or evidence of Transtentorial herniation
EVD when ?

40. Management of IVH and Hydrocephalus
•Pathophysiology
1. Clotting the cerebral aqueduct leading to obstructive
Hydrocephalus
2. Intraventricular blood and breakdown products cause
inflammation of the ependymal layer and subependymal brain
tissue
3. Inflammation and fibrosis of the arachnid granulation —> delayed
communicating hydrocephalus

41. Management of IVH and Hydrocephalus
•Recently, Large, Phase III Multicenter RCT
The use of intraventricular rTPA in patients with IVH
1. Preliminary result of the Clot lysis : evaluating accelerated
resoldution of IVH III ( CLEAR III ) —> no outcome benefit
2. Subgroup analysis showed no outcome benefit
3. Subgroup analysis showed reduced mortality in patients with
large IVH ( 2019 internetonal Stroke Conference Press release-
18 Feb 2016 )

42. Management in Surgical Intervention
•The international surgical Trial in ICH and the subsequent
STICH II
- No benefit for early hematoma evacueeation in patient with
supratentorial ICH
- Subgroup analysis shows a small survival benefit in patients
with superficial Lobar haemorrhage without significant
improvement in functional outcomes
ISTICH and STICH II Surgery

43. •Promising
1. Clinical trial in China a decade ago, 377 with BG ICH
with minimally invasive craniopuncture and needle
aspiration VS Conservative :
= Significant improvement in neuro function at 2 week and 3
month without mortality benefit
2. MIS + rTPA for ICH ( MISTIE) Phase II evaluated the utilize
of stereotactic clot
= Improve outcome in surgical patient compare with medically
manage patient
= After adding CT-guided Endoscopic surgery arm —>
Preliminary showed the newer trans-sylvan, Transinsular MIS
may yield better result due to relative sparing of cortical
function.
MIS for clot removal Surgery

44. •Indication
1. Hematoma size > 3 cm in diameter
2. Brainstem compression
3. Hydrocephalus
Treatment
= EVD placement along might not sufficient
Select patient with large lobar ICH or temporal lobe
haemorrhage may also benefit from emergent hematoma
evaluation
Posterior fossa ICH Surgery

45. Management of Perihematoma edema
•Absolute increase in Edema during the first 24-72 hours associated
with worse functional outcome at 90 days after ICH
•Asymtomatic
= maintain normal Na
No indication for routine use of Osmotic agent : mannitol or HTS
•Symtomatic
= Mannitol , HTS
= MISTIE II : significant associated with hematoma removal and
edema reduction in the surgical group
= Additional study is warranted to show the effect on outcomes.

46. Management of Perihematoma edema
•Symtomatic
1. Early continuous infusion of 3% of HTS for Na goal of 145-155
mmol/L was associated with less cerebral edema and ICP crisis
( > 20 mmHg for > 20 min or new anisocoria ) ( Small
Retrospective study )
2. HTS is slightly more effective than mannitol for the treatment of
elevated ICP ( meta-analysis 2011)
3. INTERACT2 : mannitol seems safe, but might not improved
outcome in patients with acute ICH.

47. • Real-world practice :
• The patient’s medical history and SE profile of Mannitol
and HTS may be the major factor for choosing
• 1. Congestive HF should receive a bolus of mannitol or
23.4% of HTS
• 2. Continous infusion of 3% of HTS can be used for
patient with dehydration or decrease Urine output

48. Seizure prophylaxis and treatment
•Patient with ICH have up to 16 % risk of clinical seizures within 1
weeks, with majority occurring at or near onset.
•Lobar ICH with Cortical involvement is the most important risk
factors
•28 to 31% of patients will have eletrographic seizure on
continuous EEG
•The clinical impacts of subclinical seizure is unclear
•Prophylactic phenytoin usage has been associated with worse
outcome
•No association between clinical seizure and Neurological outcome
or mortality
•Continuous EEG should be considered for ICH with depressed
mental status out of proportion to the degree of Brain injury
•Clinical seizure should be treated with Anti-epileptic drug

49. Glucose management
Hyperglycemia on admission is associated with worse Morbidity and
Mortality independent of the presence of Diabetes
Tight Glucose control with target glucose 80 -110 mg/dL increase
Hypoglycemia and risk of morbidity and Mortality
Conclusion :
Target glucose level at 100-150 mg/dl for patient with ICH

50. Fever control
Fever is common after ICH :
•Particular with Intraventricular extension —> poor outcome
•Retrospective study : fever > 38.3 degree despite Paracetamol
•Therapeutic normothermia was shown to be associated with
increase duration of sedation, Ventilator and NEuro-ICU Length of
stay without discharge outcome benefit.
•Normothermia or Hypothermia should not be used after ICH
except in the setting of clinical trails.

51. DVT prophylaxis and Treatment
ICH and rate of symptomatic DVT at 1-5%
The incident of symptomatic pulmonary embolism ( PE ) is 0.5-2%.
Up to half of the PE are fatal

52. DVT prophylaxis and Treatment
Guidelines publisher by Neurocritical care Society in December 2015
- Initiation of mechanical VTE prophylaxis : intermittent pneumatic
compression ( IPC ) devices at the time of admission , Graduated
compression stocking ( GCS )
- LMWH should be started in patient with stable hematoma within
48 hours of admission.
- Mechanical VTE Prophylaxis should be continued after initiation of
Pharmacological prophylaxis
- Patient with DVT or PE should be considered for systemic
anticoagulation depending on stability of the hematoma , cause of
haemorrhage and time since presentation
* if systemic anticoagulation is contraindication , IVC filter should be
considered.

53. Prognosis : the past
• Factor that may affect outcome after ICH
1. Hematoma volume and location
2. Hematoma expansion
3. Age
4. GCS score on presentation
5. IVH extension
6. Anticoagulant use
The ICH score was developed to predict 30 day mortality rate and functional
outcomes at 1 years

54. Current AHA/ASA guideline
• Recommend early and aggressive care after ICH and
postponement of any new DNR orders until at least the
second full day of treatment
• Patients with pre-existing DNR order are excluded from
this recommendation
• However, DNR status should not limit appropriate medical
and surgical intervention, unless explicitly indicated.

55. ICH is a medical emergency
High risk of Morbidity and Mortality
Recent advance in early diagnosis
Neurocritical care
Improved survival