overview of management hypertensive intracerebral bleed

1. HYPERTENSIVE INTRACEREBRAL BLEED
OVERVIEW OF MANAGEMENT
Dr Swapnil Samadhiya
SR DM Neurology
GMC KOTA

2. • More than 1 million annually worldwide , deadliest & most
disabling(Qureshi AI et al, N Engl J Med2001;344:1450–60)
• ∼10–15% of all stroke (Mozaffarian D et al, Circulation2015;131:e29–322)
• m/c risk factor -Uncontrolled hypertension (HTN) Ariesen MJ et al, Stroke
2003;34:2060–5
• ∼70–80% cases,spontaneous rupture of small vessels by HTN.Martini
SR et al, Neurology2012;79:2275–82
• Incidence higher Asians (limited primary care for HTN,non-
compliance) van Asch CJ et al, Lancet Neurol2010;9:167–76

3. Intracerebral hemorrhage
Small ICH
• Readily survivable with
good medical care.
Zahuranec DB et al, J Neurol Neurosurg
Psychiatr2006;77:340–4
Large ICH
• Multidisciplinary care
essential
• Specialised neurocritical
care team
Hospital stay duration and
mortality reduction
Suarez JI et al Crit CareMed2004;32:2311–7

4. • Hypertension- non lobar ICH more common than lobar ICH
• Most common locations of hypertensive ICH are the putamen,
thalamus, subcortical white matter, pons and cerebellum
Martini SR, Flaherty ML, Brown WM,et al. Risk factors for intracerebral hemorrhage differ according to
hemorrhage location. Neurology2012;79:2275–82

6. ED algorithm for early diagnosis and emergent intervention

7. EARLY DIAGNOSIS
• Rapid diagnosis,crucial for appropriate care and better
functional outcomes.
• Suspect –Sudden onset, severe headache, vomiting, elevated
systolic blood pressures or decreased level of consciousness.
Smith EE et al, Neuroimaging Clin N Am2005;15:259–72, ix
• Non-contrast head CT is highly sensitive and specific for ICH
and is the key to early diagnosis. Orito k,et alStroke2016;47:958–63

8. 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

9. 24-
48
12-240-3 6-123-6
hours from
onset
Stroke 1996;27:1783-87
Is it expanding?

10. Spot sign
Wada et al., 2007

11. • 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)
A x B x C
Calculating ICH volume
2

12. ICH volume
> 30cc 1
< 30cc 0
Intraventricular
extension
Yes 1
No 0
Infratentorial location
Yes 1
No 0
Age
> 80 1
< 80 0
Glasgow coma scale
3-4
5-12
13-15
2
1
0
Total score 0-
6
Godoy, D. A. et al. Stroke 2006
Score 30-day mortality
0 0%
1 13
2 26
3 72
4 97
5, 6 100
ICH score

13. 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

14. Preventing hematoma expansion
• Blood pressure control
• Reversing INR
• Platelet transfusion
• Metabolic

15. INTERACT 2 trial
• 2839 Patients within 6
hours of onset of ICH
• Treatment arm: SBP <140
• Control arm: SBP <180
• Intensive blood pressure
lowering –better
functional outcome at 90
days (MRS)
• Death and severe disability
similar

16. Systolic BP time trends
1 hour - Δ14 mmHg (P<0.0001)
6 hour - Δ14 mmHg (P<0.0001)
Intensive group to target
(<140mmHg)
462 (33%) at 1 hour
731 (53%) at 6 hours
MeanSystolicBloodPressure(mmHg)
0
110
120
130
140
150
160
170
180
190
200
R 15 30 45 60 6 12 18 24 2 3 4 5 6 7
Standard
Intensive
////
Minutes Hours Days / Time
164
153
150
139
am pm am pm am pm am pm am pm am pm
P<0.0001
beyond 15mins
Target level
INTERACT 2: results

17. ATACH-2 trial
• 1000 patients with acute ICH
randomly assigned (within 4.5
hours) to a target SBP of 110
to 139 mmHg or a target SBP
of 140 to 179 mmHg
• No differences in death or
disability rates
• Rates of renal adverse events
were higher in the intensive
treatment group (9 versus 4
percent).

18. Meta-analysis with individual patient data of INTERACT2
and ATACH-2 trials
• Patients who achieved early, stable systolic blood pressure
reduction in the first 24 hours to levels as low as 120 to 130
mmhg had more favorable outcomes
Moullaali TJ, Wang X, Martin RH, et al. Blood pressure control and clinical outcomes in acute intracerebral haemorrhage:
a preplanned pooled analysis of individual participant data. Lancet Neurol 2019; 18:857.

19. BP Control(AHA Statement)
• SBP between 150-220 mm
Hg
• Without contraindication to
acute BP treatment
• Lowering of SBP to 140 mm
Hg is safe (class1; Level of
Evidence A)
• Improving functional
outcome (class 2a; Level of
Evidence B)
• SBP>220 mm Hg
• Consider aggressive
reduction of BP
• SBP of 140 to 160 mmHg is
a reasonable target
• Continuous intravenous
infusion and frequent BP
monitoring (class 2a; level
of evidence C)

20. Useful intravenous agents for controlling blood pressure

22. Intracranial pressure management
• Increased intracranial pressure result from-
1. Hematoma
2. Mass effect(surrounding edema/hydrocephalus)
• Basic measures
1. Head Elevation 30 degrees
2. Mild sedation(as needed for comfort)
3. Avoidance(endotracheal tube holder),securement device ties,
constrictive central line dressings, twisting of the head might
constrict cervical veins
4. Normal saline(maintenance and replacement fluids)hypotonic fluids
contraindicated
Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A
Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032

23. 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

24. Invasive ICP Monitoring
• Glasgow coma scale (GCS) score <8
• Clinical evidence of transtentorial herniation
• Significant intraventricular hemorrhage
• Hydrocephalus
• Goal -cerebral perfusion pressure (CPP) of 50 to 70 mmHg
• High quality data lacking

25. • Rapid, noninvasive test
• Measuring optic nerve sheath diameter using ocular ultrasound is an
accurate method for detecting elevated ICP
Dilated op
Optic nerve sheath measuring 5.3 mm in a patient
Increased intracranial pressure
Patterson DF , Ho ML, Leavitt JA, et al. Comparison of Ocular Ultrasonography and Magnetic Resonance Imaging for Detection of
Increased Intracranial Pressure. Front Neurol 2018; 9:278.

26. Cerebrospinal fluid drainage
• Reduce elevated ICP,reasonable for patients
1. Hydrocephalus
2. Trapped ventricle
3. Poor GCS patients
Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of
Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the
American Heart Association/American Stroke Association. Stroke 2015; 46:2032

27. Osmotic therapy
• Hypertonic saline or mannitol
• No compelling evidence to support the superiority of either
agent
• Some studies suggest that hypertonic saline is more effective
Kamel H, Navi BB, Nakagawa K, et al. Hypertonic saline versus mannitol for the treatment of elevated
intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med 2011; 39:554

28. Mannitol Hypertonic saline
• Quick and effective
• Initial bolus of 0.5 to 1 g/kg,
f/b repeated infusions of 0.25
to 0.5 g/kg every 4 to 12
hours,monitor serum
osmolality
• Goal-plasma hyperosmolality
(300 to 310 mosmol/kg)
• Avoid Plasma osmolal gap > 55
mosmol/kg &dose > 250 mg/kg
every four hours
• Reversible acute renal failure
Ropper AH. Management of raised intracranial pressure
and hyperosmolar therapy. Pract Neurol 2014;
14:152
• 3 %, m/c,continuous infusion (
can given intermittent bolus),
23.4 %(intermittent bolus)
• Sodium goal - 145 to 155 meq/L
• Circulatory overload,pulmonary
edema,non-anion gap
metabolic acidosis(chloride)

29. Salvage therapies
• Reduce ICP if cerebrospinal fluid drainage or osmotic therapy
fail to lower ICP
1. Pharmacologic coma
2. Hyperventilation
3. Neuromuscular blockade

30. Pharmacologic coma
• Reduce cerebral metabolism
Pentobarbital
• Severe side effects(arterial hypotension),variable benefit,avoid
• Continuous monitoring with electroencephalography during
treatment, dose titrated to a burst-suppression pattern
Propofol-
• Loading dose of 1 to 3 mg/kg, infusion5 to 50 mcg/kg per minute,
with a maximum dose of 200 µg/kg per minute
• Hypotension,acute refractory bradycardia, metabolic acidosis,
cardiovascular collapse, rhabdomyolysis, hyperlipidemia, renal
failure,hepatomegaly
Schwab S, Spranger M, Schwarz S, Hacke W. Barbiturate coma in severe hemispheric stroke: useful
or obsolete? Neurology 1997; 48:1608

31. Hyperventilation
• Rapid lowering induce cerebral vasoconstriction
• Effect lasts few hours
• (Paco2 ) goal 30 to 35 mmhg.
• More aggressive hyperventilation (paco2 of 26 to 30 mmhg)brain
ischemia and worse outcomes
• Reserve for refractory
• Acute brain herniation until more definitive therapies can be
implemented
Freeman WD. Management of Intracranial Pressure. Continuum (Minneap Minn) 2015;
21:1299

32. Neuromuscular blockade
• Not responsive to analgesia and sedation.
• Muscle activity increase ICP,raising intrathoracic pressure,reducing
cerebral venous outflow
• Increased risk of pneumonia and sepsis
• Ability to evaluate the neurologic status is lost once the patient is
paralyzed

33. • 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 for ASA use?

34. 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)

35. • 2300 subjects, within
eight hours of symptom
onset
• At 90 days, no difference
in functional status or
mortality between the
two treatment groups,
despite early reductions
in hematoma growth (at
day 2) and death (at day
7) for the tranexamic
acid group.

36. • 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
• Reduced ICH growth with 80 mcg/kg vs placebo
• Time mattered: earlier treatment => less growth
NEJM 2008;358:2127-2137
Factor VII for acute ICH
-6
-5
-4
-3
-2
-1
0
<2 hours <3 hours <4 hours
Hematoma
volume
(ml) vs
placebo

37. 90 day death/severe disability
• No clinical benefit
• MI and ischemic
stroke absolute risk
increased 5%
AHA Statement
• Increase
thromboembolic
risk
• Not recommended
(class 3; Level of
Evidence A)

38. Metabolic
• Hyperglycemia and hypoglycemia should be avoided( 140 to 180
mg/dL) (class 1; Level C)
• 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)
• Dysphagia screen all patients before initiating oral intake to reduce
pneumonia risk (class 1; Level B) ,GCS <8 be intubated to decrease
the risk of aspiration
• Proton pump inhibitors, histamine-2 receptor antagonists ass/w
increased risk hospitalacquired pneumonia, Clostridioides difficile
infection, other enteric infections; routine use should be avoided

39. Pathogenesis of secondary brain insult of hypertensive intracerebral
hemorrhage

40. Complications of ICH
• Seizures
• Hydrocephalus
• DVT/PE

41. Seizures
• Approx.15 percent
• Lobar >Deep hemorrhage
• Prophylactic antiseizure medication is not recommended (class 3;
Level B)
• Clinical Seizures should be treated with antiseizure medication (Class
1;Level A)
• Continuous EEG monitoring ,depressed mental status that’s out of
proportion to degree of brain injury (Class 2a; Level C) and should be
treated with antiseizure medication if found to have electrographic
seizures on EEG (class 1; Level C)

42. Hydrocephalus
•Headache
•Vomiting
•Drowsiness → Coma
•EVD- decreased level
of consciousness (class
2a; Level B)

43. DVT
• Risk of DVT in hemiplegic patients is 10-50% during acute
hospitalization
AHA STATEMENT
• 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.

44. Intraventricular Hemorrhage
• Intraventricular administration of rtPA ,fairly low complication rate,
efficacy and safety uncertain (class 2b; Level B)
• Efficacy of endoscopic treatment of IVH is uncertain (class 2b; Level
B)

45. • 1033 patients randomized
• 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
STICH Trial
Mendelow et al. Lancet 2005

46. STICH Results

47. STITCH II trial

48. Surgery
• Cerebellar hemorrhage ,deteriorating neurologically , brain stem
compression,hydrocephalus surgical removal as soon as possible
(class 1; Level C)
• Initial treatment with ventricular drainage rather than surgical
evacuation is not recommended (class 3; Level C)
• Supratentorial ICH, usefulness of surgery not well established
(class2b; Level A)
• Policy of early hematoma evacuation not clearly beneficial compared
to hematoma evacuation when patient deteriorates (Class 2b; Level
A)

49. Surgery
• Indication vary with the site of the bleed
• Cerebellar hemorrhage >3 cm diameter, volume >14 cm3 ,
deteriorating neurologically ,brainstem compression,hydrocephalus
• 2019 meta-analysis matched 152 patients who had surgical
hematoma evacuation with 152 patients who had conservative
treatment
• Surgical hematoma evacuation increased probability of survival at
three months(78 % vs 61%)
• Overall likelihood of a favorable functional outcome similar
Kuramatsu JB, Biffi A, Gerner ST , et al. Association of Surgical Hematoma Evacuation vs Conservative T reatment
With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage. JAMA 2019; 322:1392

50. Supratentorial hemorrhage
• Controversial
• Indications not been conclusively defined
• Reserve surgical therapy for patients with life-threatening mass effect
from supratentorial ICH
• Limited data -reduce mortality(comatose,large hematoma with
significant midline shift, elevated intracranial pressure (ICP) refractory
to medical management)
• Routine evacuation of supratentorial ICH in the first 96 hours is not
recommended
Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous
Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association. Stroke 2015; 46:2032

51. Open craniotomy
• 2008 meta-analysis reviewed 10 randomized trials including 2059
patients
• Associated with a reduced risk of death and dependency (odds ratio
0.71; 95% ci 0.61 to 0.91)
• Benefit was not robust, and there was significant heterogeneity for
death as an outcome
• STICH trial, largest, 503 patients, median time to surgery was 30
hours after hemorrhage onset, favorable outcome at six months

52. Minimally invasive techniques
• MISTIE III no clear benefit
• 516 patients with spontaneous,
supratentorial ICH of ≥30 mL
• At one year , the number of
patients who achieved a good
functional outcome similar for
the minimally invasive surgery
group compared with the
standard care group (45 versus
41 percent)
• Mortality was lower in the
minimally invasive surgery (19
versus 26 percent)

53. SECONDARY TREATMENT ISSUES
• Resumption benefit of
aspirin (non-lobar ICH>
lobar ICH)
• At 10 days, rebleeding
unlikely typically should be
not be restarted until at
least one to two weeks
after ICH.
• As soon as 48 hours, after
ICH in stable patients who
require it. Hemphill JC 3rd et al,
Stroke 2015; 46:2032
• Lower dose (30 to 160 mg
daily) effective and safer

54. Resumption of anticoagulation
• Avoidance of long term AC for nonvalvular AF 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 without mechanical valves, might
decrease ICH recurrence (class 2b; Level B)
Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous
Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association. Stroke 2015; 46:2032

55. Secondary prevention
• PROGRESS trial
• 6000 patients with prior
cerebrovascular events
• Mean baseline blood
pressure of 147/86,a modest
reduction in blood pressure
of 9/4 mmhg decreased the
rate of ICH by 50%(95% CI
26-67)

56. • SPARCL trial statins
might increase the risk
of ICH in patients with
a previous ischemic
stroke or ICH
• Conflicting data, it
seems to be
reasonable to weigh
the benefits and
possible risks of statin
therapy in individual
patients

57. PROGNOSIS
Risk factors for poor outcomes
• Increasing age
• Decreasing Glasgow Coma Scale (GCS) score(eight or less),Early
neurologic deterioration within 48 hours after ICH onset
• Increasing ICH volume(>60 cm3 on initial CT) ,Hematoma
growth(first 24 hours)10 % increase,5 % more likely to die
• Intraventricular hemorrhage
• Deep or infratentorial ICH location
• Preceding oral anticoagulation therapy, and possibly antiplatelet
therapy

58. PROGNOSIS
Risk factors for poor outcomes
• Early withdrawal of support
• Elevated admission blood glucose
• Lower serum levels of low density lipoprotein cholesterol (LDL-C)
• Elevated C-reactive protein levels
• Extensive white matter lesions on CT or magnetic resonance imaging
(MRI)

59. GCS score-Useful predictor of 30-day mortality
GCS scores
• 3 to 4
• 7 to 10
• 11 to 12
• 13 to 14
• 15
Predicted 30-day survival rates
• 5%
• 35 %
• 55 %
• 70%
• 90%

60. The FUNC score. Stroke 2008; 39:2304. DOI:
10.1161/STROKEAHA.107.512202
• No patient assigned a FUNC score ≤4 achieved functional
independence, whereas >80 percent with a score of 11 died

61. ICH Recurrence
Risk factors for recurrent ICH
1. Uncontrolled hypertension
2. Lobar location of initial ICH
3. Older age
4. Male gender
5. Ongoing anticoagulation
6. Apolipoprotein E epsilon 2
or epsilon 4 alleles
7. Greater number of
microbleeds on MRI
8. Ischemic stroke history
9. Black race
10. Hispanic ethnicity
Poon MT , Fonville AF , Al-Shahi Salman R. Long-term prognosis
after intracerebral haemorrhage: systematic review and
meta-analysis. J Neurol Neurosurg Psychiatry 2014;
85:660

62. REFERENCES
1. AHA/ASA Guidelines for the Management of Spontaneous Intracerebral
Hemorrhage
2. Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the
Management of Spontaneous Intracerebral Hemorrhage: A Guideline for
Healthcare Professionals From the American Heart Association/American
Stroke Association. Stroke 2015; 46:2032
3. Kuramatsu JB, Biffi A, Gerner ST , et al. Association of Surgical Hematoma
Evacuation vs Conservative T reatment With Functional Outcome in Patients
With Cerebellar Intracerebral Hemorrhage. JAMA 2019; 322:1392
4. Poon MT , Fonville AF , Al-Shahi Salman R. Long-term prognosis after
intracerebral haemorrhage: systematic review and meta-analysis. J Neurol
Neurosurg Psychiatry 2014; 85:660
5. Martini SR, Flaherty ML, Brown WM,et al. Risk factors for intracerebral
hemorrhage differ according to hemorrhage location.
Neurology2012;79:2275–82
6. Freeman WD. Management of Intracranial Pressure. Continuum (Minneap
Minn) 2015; 21:1299
7. Ropper AH. Management of raised intracranial pressure and hyperosmolar
therapy. Pract Neurol 2014; 14:152

63. THANK YOU