Evidence-Based Management of Intraparenchymal Hemorrhage

Assistant Professor, Dept of Neurosurgery, University of PittsburghBradley A. Gross, MD

October 2019

• Background• Assessment & Diagnosis• Medical Management• Surgical Management

ICH

Background

• ICH accounts for 20% of all stroke• Most common form of hemorrhagic stroke

• Meta Analysis of 36 Studies• Incidence of 24.6/100,000 person-years

• No Sex Predilection• Incidence Increases With Age

• Median 1 Month Fatality 40.4% (13.1-60%)

• Primary IPH• HTN• CAA

• Secondary IPH• AVM• dAVF• Cav Mal• Mycotic Aneurysm• Venous Sinus Thrombosis• Moyamoya• Vasculitis• Hemorrhagic Tumor• Hemorrhagic Ischemic Stroke

Risk Factor OR of ICH

Self-reported history of HTN or SBP > 160/90 9.18 (99% CI 6.80-12.39)

Current Smoker 1.45 (99% CI 1.07-1.96)

1-30 Drinks Per Month> 30 Drinks Per Month or Binge Drinker

1.52 (99% CI 1.07-2.16)2.01 (99% CI 1.35-2.99)

Non-HDL Cholesterol (Third vs First Tertile)HDL Cholesterol (Third vs First Tertile)

0.50 (99% CI 0.34-0.72)1.91 (99% CI 1.29-2.83)

• Case-Control Study in 22 Countries• 3000 Cases (663 ICH) with 3000 controls

110 patients all undergoing autopsy with ICH

• Background• Assessment & Diagnosis• Medical Management• Surgical Management

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Presentation

• Ischemic/Hemorrhagic Stroke• Acute Onset• Focal Deficit• HTN / Blood Pressure Lability

• Hemorrhagic Stroke• Headache• Nausea/Vomiting• Depressed Mental Status

• 22% Deteriorate in Transport • Crit Care Med 2008; 36: 172-175

• 23% GCS 13-15 in ED deteriorate at least 2 points in ED• Predictors: Antiplatelet use, ictus to ED arrival < 3 hours, Temp at least 37.5C, IVH,

2 mm or more MLS• Acad Emerg Med 2012; 19: 133-138

• ED Evaluation: Time of Onset, PMH (HTN, Anticoagulant), Exam

Diagnosis

• Rapid Imaging (Class I, Level A)• Advanced Imaging For Underlying Lesion (Class IIa, Level B)

• CTA• Positive Predictors (JNS 2012; 117: 761-766):

• Age < 65 (OR 16.36)• Female Sex (OR 14.9)• Nonsmoker (OR 103.8)• IVH Presence (OR 9.42)• No HTN (OR 515.78)• HTN, older than 65 with basal ganglia / cerebellar bleed > negative CTA

• MRI• DSA

All patients within 6 hours of symptom onset

• 63yo F HTN, HL, DM, smoker

Assessment

• Baseline Severity Score Should Be Performed – Class I, Level of Evidence B

ICH Score Factors MortalityGCS Score (3-4, 2 points; 5-12, 1 point) 0 points = 0%Age at least 80 (1 point) 1 point = 13%Infratentorial Hemorrhage Origin (1 point) 2 points = 26%Volume of at least 30 cc (1 point) 3 points = 72%Intraventricular Blood (1 point) 4 points = 97%

5 points = 100%

Hemphill JC, et al. The ICH Score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001; 32: 891-897.

• Background• Assessment & Diagnosis• Medical Management• Surgical Management

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Initial / Medical Management

• Secure Airway As Indicated• Avoid Hyper/Hypoglycemia (Class I, Level C)• AED if Seizure (Class I, Level A)• Screening EKG and Tn (Class IIa, Level C)• BP Control (< 140)• Coagulopathy Management• ICU / Stroke Unit Admission (Class I, Level B)• No: Prophylactic AED, rVIIa, Tranexamic Acid, Steroids

• GOAL: Mitigate Hematoma Growth, Improve Outcome

817 patients with IPHHematoma Expansion in 19% (6 cc or by 33%)

No Impact On Hematoma Growth:Age, SexAntiplatelet UsagePresenting GCSAmyloidICH LocationPresence of IVH

• INTEnsive blood pressure Reduction in Acute Cerebral Hemorrhage (INTERACT2)• INTERACT-1 RCT in Lancet Neurol 2008 of 500 patients with less hematoma growth with SBP < 140

• Spontaneous “nonmassive” ICH, GCS 6+

• 1382 Patients SBP 110-139 vs 1412 Patients SBP 140-179 • Initiated within 6 hours after bleed for next 7 days

• mRS 3-6 in 52.0% vs 55.6% at 3 months (p = 0.06); meets significance in ordinal analysis

• Serious Adverse Events 23.3% vs 23.6%.

• Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2)• ATACH – feasibility and safety of three BP tiers in 60 patients (Crit Care Med 2010)

• Spontaneous Supratentorial ICH < 60 cc, GCS 5+

• 500 Patients SBP 110-139 vs 500 Patients SBP 140-179 via cardene gtt• Initiated within 4.5 hours after symptom onset for next 24 hours with SBP > 180

• mRS 4-6 in 38.7% vs 37.7% at 3 months

• Overall Treatment-Related Serious Adverse Events 1.6% vs 1.2%

• Hematoma Expansion (33% or more at 24 hours) 18.9% vs 24.4% (p = 0.08)

• Renal Adverse Events 9% vs 4% (p = 0.002)

• Mean SBP 128.9 vs 141.1 in two hours (150 vs 164 in INTERACT2)

• Achieved systolic blood pressure was continuously associated with functional outcome.

Coagulopathy Management

• Repletion for Coagulation Factor Deficiency/Thrombocytopenia (Class I Level C)

• Reversal of Anticoagulation• If VKA: PCC (Class IIb Level B), Vit K (Class I Level C)

• Hematoma growth: 19% if PCC vs 33% FFP• FFP = fluid overload, similar thromboembolic complications

• Protamine Sulfate for Heparin (Class IIb Level C)• ? Reversal of Antiplatelet

• Spontaneous supratentorial ICH within 6 hrs of Sx

• Used antiplatelet for at least 7 days prior• 78% Cox-I, 16% Cox-I + Dipyridamole, 3% ADP-I, 2% Cox-I + ADP-I

• GCS at least 8• 97 transfusion vs 93 standard care

• Alive at 3 months 68% vs 77% (OR 0.62, 95% CI 0.33-1.19)• mRS 4-6 at 3 months 72% vs 56% (OR 2.04, 95% CI 1.12-3.74)• mRS 3-6 at 3 months 78% vs 82% (OR 1.75, 95% CI 0.77-3.97)• Median ICH growth at 24 hours 2.01 vs 1.16 (p = 0.81)• Serious adverse event: 42% vs 29%.

537 adults taking antiplatelet/anticoagulant with ICHRandomized to restarting antiplatelet in 24 hrs at least 24 hrs post ictusRecurrent Symptomatic ICH: 4% vs 9% (p = 0.06)Major Hemorrhagic Events: 7% vs 9% (p = 0.27)Major Occlusive Vascular Events: 15% vs 14% (p = 0.92)

Recurrent Symptomatic ICH / Stroke: 4% vs 9% (p = 0.04)

ICU / Stroke Unit Admission (Class I, Level B)

• Greater chance of independence!• Terent et al. JNNP 2009:

• 8206 patients in stroke unit vs 2871 on standard ward• 3 month death / dependence 59% vs 75% • (OR 0.59, 95% CI 0.53-0.67)

Early dysphagia screen (Class I, Level B)Intermittent Pneumatic Compression (Class I, Level A)

CLOTS (Clots in Legs Or sTockings after Stroke), Lancet 2013; 382: 516-524:DVT rate: 8.5% vs 12.1% (p < 0.05)

SC Heparin / LMWH 1-4 days after stability (Class IIb, Level B)

• UFH/LMWH within 24-96 hr• DVT rate: 3.3% vs 4.2%, (RR 0.77, 95% CI 0.44-1.34)• PE rate: 1.7% vs 2.9% (RR 0.37, 95% CI 0.17-0.80)• Hematoma Enlargement rate: 8.0% vs 4.0% (RR 1.42, 95% CI 0.57-3.53)• Mortality 16.1% vs. 20.9% (RR 0.76, 95% CI 0.57-1.03)

• Background• Assessment & Diagnosis• Medical Management• Surgical Management

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Neurosurgical Consultation

• Hydrocephalus• 23% of all patients in STICH, 55% if IVH• EVD

• “Decreased LOC” (Class IIa Level B)• GCS < 9 (Class IIb, Level C)

• Surgical Evacuation• > 3 cm Cerebellar IPH (Class I, Level B)

• Deteriorating• Brainstem Compression/Hydrocephalus

• Supratentorial IPH• Large Hematoma with shift (Class IIB, Level C)

6 mo mRS 2

• 1003 patients from 83 centres in 27 countries

• Minimum hematoma diameter of 2 cm, GCS at least 5• Early surgery (n = 503) or conservative treatment (n = 530)

• 6 month Favourable Outcome: 26% vs 24% • GOS good recovery / moderate disability• (OR 0.89, 95% CI 0.66-1.19)

• 601 patients from78 centres in 27 countries

• Superficial Hematoma 10 -100 cc (1 cm from surface), GCS 8+• Early surgery (n = 307) or conservative treatment (n = 294)

• 6 month Unfavourable Outcome: 59% vs 62% (p = 0.37)

• Spontaneous 30 cc + bleed• MIS: Image Guided Placement of Catheter, Aspiration, rtPA

• rtPA 1.0 mg q8h up to 9 doses

• 250 MIS plus rtPA vs 249 Medical Care• mRS 0-3 at 1 yr: 45% vs 41% (p = 0.33)

• 39 cases• Median GCS 10, 36 cc hematoma volume• 52% mRS 2 or less, no mortality

ENRICH

• Early miNimally invasive Removal of IntraCerebral Hemorrhage• Age 18-80, GCS 5-14, 30-80 cc IPH• Brainpath vs medical management within 24 hours• Primary outcome utility-weighted mRS at 180 days

Secondary ICHEtiology Dx Tx

AVM CTA / DSA Surgery / SRS / Embolization

dAVF CTA / DSA Embolization / Surgery

Cavernous Malformation MRI Surgery

Distal/Mycotic Aneurysm CTA / DSA Embolization/ Surgery

Venous Sinus Thrombosis CTV Thrombectomy/Anticoagulation

Moyamoya CTA / DSA Revascularization

Vasculitis CTA / DSA Rx

Tumor MRI / Surgery Surgery / SRS

Summary

• ICH accounts for 20% of all Stroke• Median 1 month fatality 40%• ICH Risk Factors: HTN, Smoking, EtOH, HDL Cholesterol• CAA recurrent ICH rate: 7.4% / yr vs 1.1% / yr• CAA Factors: SAH, Finger projections, Apoe4• Hemphill Score: GCS, Age > 80, Infratentorial, IVH, > 30 cc• SBP < 140, Coagulopathy Management, ICU Admission• EVD for hydrocephalus, Evacuate/Decompress if Cerebellar > 3 cm / Herniation• Minimally Invasive Trials for Supratentorial Bleeds