Intracerebral Hemorrhage & high ICP management Emergency Lecture Series July 10, 2013 Abdulla Alkuwaiti R2

Intracerebral Hemorrhage & high ICP management

Emergency Lecture Series

July 10, 2013

Abdulla Alkuwaiti R2

Content

• Pathophysiology• Epidemiology• Clinical features• Causes/Risk factors• Types of ICH• Radiological Findings• Management/ including increase

ICP• Prognosis

Pathophysiology

• Thrombin and iron, released upon red blood cell (RBC) lysis, are 2 major factors causing brain injury after ICH.

• Thrombin at high concentrations kills neurons and astrocytes in vitro.

• Hemoglobin degradation can result in iron release. The iron causes marked brain edema, even in small concentration.

Ya Hua, “Intracerebral hemorrhage: introduction brain injury afteriIntracerebral hemorrhage, ther role of Thrombin and Iron” Stroke.2007; 38: 759-762

Secondary DamageSecondary Damage

Hematoma expansion≥ 80 ml fatal

Cerebral edema

Secondary injury

Epidemiology• Accounts for 15% of strokes in the West and

30% in the East• 12-15 cases per 100,000 per year• More common in Hispanics, Blacks, Asian than

in whites

Canada: 2008/2009Total 11%: AGE 20-29: 17%, 30-39: 16%, 40-49:

11%, 50-59: 12%, 60-69: 12%, 70-79: 10%, 80-89: 10%, 90+: 7%

Male 53%, female 47%

The quality of stroke care in Canada, Canadian stroke network 2011

Clinical Features

• Sudden headache +/- N & V• Smooth progressive onset over minutes

to hours • Usually during activity• Confusion• Neurodeficit: hemiplegia• Depressed level of consciousness• Seizures

Case: 26F

Post op

Post Angio

ICH ScoreICH Score

Component ICH score pointsGCS

3 - 4 2

5 - 12 1

13 - 15 0

ICH volume

≥ 30 ml 1

≤ 30 ml 0

IVH

yes 1

no 0

Infratentorial 1

Age > 80 1

Mortality and ICH ScoreMortality and ICH Score

Classification of ICHClassification of ICH

PRIMARYPRIMARY (78-88%) (78-88%) Hypertensive Hypertensive

angiopathy angiopathy (fibrohyalinosis)(fibrohyalinosis)

Amyloid angiopathyAmyloid angiopathy Anticoagulant Anticoagulant

AssociatedAssociated

SECONDARYSECONDARY AVMAVM AneurysmAneurysm CavernomaCavernoma NeoplasmNeoplasm CoagulopathyCoagulopathy

Alcoholic liver diseaseAlcoholic liver disease HemophiliaHemophilia

Hemorrhagic infarctHemorrhagic infarct Toxic-cocaineToxic-cocaine

Risk factorsRisk factors

AGE: AGE: Incidence significantly doubles with each Incidence significantly doubles with each decade after age 55. Above 80 years of age risk decade after age 55. Above 80 years of age risk increases 25 timesincreases 25 times

Gender:Gender: more common in men more common in men Race:Race: more common in blacks, hispanics, asians, less more common in blacks, hispanics, asians, less

in whitesin whites Previous CVAPrevious CVA Alcohol consumptionAlcohol consumption: >3 drinks per day increases : >3 drinks per day increases

the risk of the risk of ICH by 7 foldsICH by 7 folds Drugs: Drugs: cocaine, amphetaminecocaine, amphetamine Cigarette smoking does not increase the risk of ICHCigarette smoking does not increase the risk of ICH

Risk FactorsRisk Factors

Oral Anticoagulant: Oral Anticoagulant: warfarinwarfarin risk of bleed in risk of bleed in afib patient is 2.2% per yearafib patient is 2.2% per year

AntiplateletsAntiplatelets: ASA alone (1.3% per year risk) : ASA alone (1.3% per year risk) no significant increase in risk but ASA and no significant increase in risk but ASA and plavix together increase risk to 2.4% per year.plavix together increase risk to 2.4% per year.

rTPA: rTPA: risk of ICH is 6.4% in the next 36hrsrisk of ICH is 6.4% in the next 36hrs

Genetic predisposition Genetic predisposition

The E2 and E4 alleles of the apolipoprotein E The E2 and E4 alleles of the apolipoprotein E gene play an important role in the occurrence gene play an important role in the occurrence of certain forms of ICH as labor hemorrhagesof certain forms of ICH as labor hemorrhages

O’Donnel et al, 2000O’Donnel et al, 2000

Types of Intracerebral HemorrhageTypes of Intracerebral Hemorrhage

Putaminal hemorrhage (35%)Putaminal hemorrhage (35%) Caudate Hemorrhage (5%)Caudate Hemorrhage (5%) Thalamic Hemorrhage (10-15%)Thalamic Hemorrhage (10-15%) Mesencephalic Hemorrhages (rare)Mesencephalic Hemorrhages (rare) Pontine Hemorrhage (5%)Pontine Hemorrhage (5%) Medullary Hemorrhages (rare)Medullary Hemorrhages (rare) Cerebellar Hemorrhage (5-10%)Cerebellar Hemorrhage (5-10%) Lobar Hemorrhage (25%) Lobar Hemorrhage (25%)

IVHIVH

Extension of ICH to IVH is a common feature Extension of ICH to IVH is a common feature of caudate and thalamic hemorrhages, and of of caudate and thalamic hemorrhages, and of large putaminal and lobar hemorrhageslarge putaminal and lobar hemorrhages

Lobar HemorrhagesLobar Hemorrhages

22ndnd most common (25%) most common (25%) Nonhypertensive mechanisms: Nonhypertensive mechanisms:

Young (AVM sympathomimetic agents)Young (AVM sympathomimetic agents)

Elderly: cerebral amyloid angiopathyElderly: cerebral amyloid angiopathy Usually subcortical frontal vs parietal vs temporal Usually subcortical frontal vs parietal vs temporal

vs occipital vs occipital Seizures in up to 28% of patientsSeizures in up to 28% of patients Mortality rate is lower than other bleeds, and long Mortality rate is lower than other bleeds, and long

term functional outcome maybe better.term functional outcome maybe better.

Radiological FindingsRadiological Findings

SpotSign

Radiological FindingsRadiological FindingsSpot sign: predictor of expansion (PREDICT 2012)Spot sign: predictor of expansion (PREDICT 2012)PPV 61%NPV 78%Sensitivity 51%Specificity 85%Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (p=0·002).

Demchuk AM, Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 2012 Apr;11(4):307-14.

MRI Brain

Management of ICH

• ABC ICU admission• Early control of elevated BP• Correction of coagulopathy and platelet

abnormalities• Identification and control of urgent surgical

issues, such as threatening mass effect, intracranial HTN and hydrocephalus • Definitive diagnosis of the cause of the

hemorrhage and definitive treatment of the underling cause

General Supportive CareGeneral Supportive Care

HOB 30°HOB 30° SO2 ≥ 95%SO2 ≥ 95% Glucose control, hypoglycemia should be Glucose control, hypoglycemia should be

avoidedavoided T° control ≤ 37.5° CT° control ≤ 37.5° C Pain control, sedationPain control, sedation

Prognosis and Acute Blood PressurePrognosis and Acute Blood Pressure1

mon

th m

orta

lity

(%)

MAP (mm Hg)

Fogelhom et al, Stroke, 28: 1396-400, 1997 Okumura et al, J. Hypertension, 23: 1217-23, 2005

↑ Early Neurological Deterioration↓ Functional Outcome (90 days)

0

20

40

60

80

100

-117 118-132 133-144 145-

1 m

onth

mor

talit

y (%

)

Blood Pressure and Hematoma Blood Pressure and Hematoma EvolutionEvolution

Target max Target max SBPSBP

No No EnlargementEnlargement

Hematoma Hematoma EnlargementEnlargement

140 mmHg140 mmHg 1616 22 9%9%

p=0.025p=0.025150 mmHg150 mmHg 1414 11

160 mmHg160 mmHg 2222 8830%30%

170 mmHg 170 mmHg 88 55

Ohwaki et al, Stroke, 35: 1353-1367, 2004

Blood pressure control

• Blood pressure on initial arrival to the ER and every 15 minutes until blood pressure has stabilized, showed be corrected within 1 hour of presentation.

• Target < 180 mmHg• Close blood pressure monitoring (e.g. every 30 to 60

min) should continue for at least the first 24 to 48 hours.• There is evidence demonstrating it is safe to target

systolic blood pressure to less than 160 mmHg.

American and Best practice canadian guidelines for stroke management

BP Control Meds

• Labetalol: 10-20mg iv over 2 minutes, then 40-80mg iv every 10 min, until BP is controlled. Max dose 300mg per day. Fu heart rate, avoid bradycardia.

• Enalopril iv 0.625 to 1.2 mg every 4-6 hours• Hydralazine iv 10-20mg every 4-6 hours• Nicardipine 5mg/hr titrate by 2.5mg/hr every 5 min to a

maximum dose of 15mg/hr• Sodium Nitroprusside: it can increase ICP so to be

avoided in neurological emergencies unless everything else fails. Risk of cyanide toxicity can occur with rapid and prolonged infusion. Metabolic acidosis, elevated lactate levels and lactate/pyruvate ratios, and increased mixed venous oxygen content suggest clinical toxicity.

Antiepileptics

• Clinical seizures should be treated with antiepileptic drugs

• Patients with a change in mental status who are found to have electrographic seizures on EEG should be treated with antiepileptic drugs

• Prophylactic anticonvulsant medication should not be used


StatinsStatins

The The SPARCL trial SPARCL trial of high-dose atorvastatin of high-dose atorvastatin in secondary stroke prevention reported in secondary stroke prevention reported an an excess of ICH with active treatmentexcess of ICH with active treatment compared with placebo (55 versus 33; P0.02).compared with placebo (55 versus 33; P0.02).

2012 meta-analysis of 31 RCT 2012 meta-analysis of 31 RCT trial on statin trial on statin and risk of intracerebral hemorrhage, there and risk of intracerebral hemorrhage, there was no significant increasewas no significant increase

Reversing coagulopathies

Check Coag and platelets Correct thrombocytopenia below 100, some references

say below 75. If on ASA or plavix, should be held and transfused

platelets Warfarin should be stopped and treated with

prothrombin complex concentrate (PCC) (contains factor 2, 7, 9, 10, protein c and protein s) and Vitamin K 10 mg IV. Fresh-frozen plasma 2-6 units and Vitamin K could be used as alternative if PCC is not available

If on heparin best reversed with protamine sulfate (1.0 to 1.5 mg/1000 U heparin


Reverse anticoagulation

Dabigatran reversal may benefit from PCC but the evidence is weak and efforts should be directed toward improving renal clearance with consideration of hemodialysis in emergency situations. Rivaroxaban and apixaban are more likely to benefit from PCC administration than dabigatran but are unlikely to benefit from hemodialysis.

F Robert ‘The role of anticoagulats, antiplatelets, and their reversal strategies in the management of intracerebral hemorrhage’ Neurosurg focus 34 (5): 2013

Recombinant Factor VIIa • Within 4 hours prevents hematoma growth• Increases the risk of arterial thromboembolic • No clinical benefit for survival or outcome. • It is not recommended for use outside of clinical

trials at this time


Factor V11a

Hematoma Evolution and Hematoma Evolution and rFVIIarFVIIa

rFVIIa within 4 hours: • Dose dependent attenuation of hematoma expansion • no effect on mRS at 90 days

3.3ml4.5ml 5.8ml

Mayer et al. NEJM 2005; 352: 777-85

Treatment of ICHTTreatment of ICHT

IntubationIntubation HyperventilationHyperventilation SedationSedation Steroids: NO roleSteroids: NO role Osmotic agentsOsmotic agents

MannitolMannitol Hypertonic salineHypertonic saline

No Δ in outcomeNo Δ in outcome

Intracranial Pressure control

•Elevate the HOB to 30 degrees•Analgesia and sedation, particularly in unstable, intubated patients •ICP monitor should be considered for patients with GCS <8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus. •Osmotic diuretics (eg, mannitol and hypertonic saline solution) •neuromuscular blockade•Goal of maintaining cerebral perfusion pressure (CPP) of 50 to 70 mmHg

The ICP lowering effect of hyperventilation to a PaCO2 of 25 to 30 mmHg is dramatic and rapid. However, the effect only lasts for minutes to a few hours.

ICP control

Glucocorticoids should not generally be used to lower the ICP in patients with ICH. No improvement in outcome


ICP control

Surgical Indications

• Cerebellar bleed: >3cm, and deteriorating, vs brain stem compression, vs hydrocephalus due to ventricular obstruction

• Supratentorial ICH evacuation: Controversial• STICH trial: patients assigned to early (within 24hr)

surgical hematoma evacuation were slightly more likely to have a favorable outcome at six months compared with initial conservative treatment, but trend did not reach statistical significance.

• It should only be considered as a life saving procedure to treat refractory increases in ICP


Surgical Indications

• Favoring surgery: obtunded-stupor patients, recent onset of hemorrhage, ongoing clinical deterioration, involvement the nondominant hemisphere, location of the hematoma near the cortical surface.

• For patients presenting with lobar clots >30 mL and within 1 cm of the surface evacuation of supratentorial ICH by standard craniotomy might be considered

• No clear evidence at present indicates that ultra-early removal of supratentorial ICH improves functional outcome or mortality rate.


Intra-ventricular HemorrhageIntra-ventricular Hemorrhage

EVDEVD

Intra- ventricular rtpa (CLEAR)Intra- ventricular rtpa (CLEAR)

Case 55F presented with Case 55F presented with Headache and LOCHeadache and LOC

PROGNOSISPROGNOSIS

Mortality 35-52% in the first 30 days Mortality 35-52% in the first 30 days and half of them in the first 2 daysand half of them in the first 2 days

Factors Affecting PrognosisFactors Affecting Prognosis

Volume of hemorrhageVolume of hemorrhage Hematoma growthHematoma growth Early Neurological deterioration within 48hrEarly Neurological deterioration within 48hr Oral AnticoaglantsOral Anticoaglants GCS on presentationGCS on presentation AgeAge Hemorrhage locationHemorrhage location Intraventricular hemorrhageIntraventricular hemorrhage

Summary ICH Management

• Early control of elevated BP• Correction of coagulopathy and platelet

abnormalities• Identification and control of urgent surgical

issues, such as threatening mass effect, intracranial HTN and hydrocephalus

• Definitive diagnosis of the cause of the hemorrhage and definitive treatment of the underling cause

Questions

Modified Rankin ScaleModified Rankin Scale

Documents

Intracerebral Hemorrhage & high ICP management Emergency Lecture Series July 10, 2013 Abdulla Alkuwaiti R2