Intracerebral Hemorrhage high ICP management Emergency Lecture Series

Intracerebral Hemorrhage & high ICP management Emergency Lecture Series July 10, 2013 Abdulla Alkuwaiti R 2

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 afteri. Intracerebral hemorrhage, ther role of Thrombin and Iron” Stroke. 2007; 38: 759 -762

Secondary 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: 2008/2009 Total 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: 26 F

Post op

Post Angio

ICH Score Component ICH score points GCS 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 Score

Classification of ICH SECONDARY PRIMARY (78 -88%) n n n Hypertensive angiopathy (fibrohyalinosis) Amyloid angiopathy Anticoagulant Associated n n n n AVM Aneurysm Cavernoma Neoplasm Coagulopathy n Alcoholic liver disease n Hemophilia Hemorrhagic infarct Toxic-cocaine

Risk factors n n n n AGE: Incidence significantly doubles with each decade after age 55. Above 80 years of age risk increases 25 times Gender: more common in men Race: more common in blacks, hispanics, asians, less in whites Previous CVA Alcohol consumption: >3 drinks per day increases the risk of ICH by 7 folds Drugs: cocaine, amphetamine Cigarette smoking does not increase the risk of ICH

Risk Factors Oral Anticoagulant: warfarin risk of bleed in afib patient is 2. 2% per year n Antiplatelets: ASA alone (1. 3% per year risk) no significant increase in risk but ASA and plavix together increase risk to 2. 4% per year. n r. TPA: risk of ICH is 6. 4% in the next 36 hrs n

Genetic predisposition n The E 2 and E 4 alleles of the apolipoprotein E gene play an important role in the occurrence of certain forms of ICH as labor hemorrhages O’Donnel et al, 2000

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

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

Lobar Hemorrhages 2 nd most common (25%) n Nonhypertensive mechanisms: Young (AVM sympathomimetic agents) Elderly: cerebral amyloid angiopathy n Usually subcortical frontal vs parietal vs temporal vs occipital n Seizures in up to 28% of patients n Mortality rate is lower than other bleeds, and long term functional outcome maybe better. n

Radiological Findings Spot Sign

Radiological Findings Spot sign: predictor of expansion (PREDICT 2012) n PPV 61% n NPV 78% n Sensitivity 51% n Specificity 85% n 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 Care v HOB 30° v SO 2 ≥ 95% v Glucose control, hypoglycemia should be avoided v T° control ≤ 37. 5° C v Pain control, sedation

Prognosis and Acute Blood Pressure 1 month mortality (%) ↑ Early Neurological Deterioration ↓ Functional Outcome (90 days) MAP (mm Hg) Fogelhom et al, Stroke, 28: 1396 -400, 1997 Okumura et al, J. Hypertension, 23: 1217 -23, 2005

Blood Pressure and Hematoma Evolution Target max No SBP Enlargement Hematoma Enlargement 140 mm. Hg 16 2 150 mm. Hg 14 1 160 mm. Hg 22 8 8 5 170 mm. Hg 9% p=0. 025 30% 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 mm. Hg • 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 mm. Hg. American and Best practice canadian guidelines for stroke management

BP Control Meds • Labetalol: 10 -20 mg iv over 2 minutes, then 40 -80 mg iv every 10 min, until BP is controlled. Max dose 300 mg per day. Fu heart rate, avoid bradycardia. • Enalopril iv 0. 625 to 1. 2 mg every 4 -6 hours • Hydralazine iv 10 -20 mg every 4 -6 hours • Nicardipine 5 mg/hr titrate by 2. 5 mg/hr every 5 min to a maximum dose of 15 mg/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 American and Best practice canadian guidelines for stroke management

Statins The SPARCL trial of high-dose atorvastatin in secondary stroke prevention reported an excess of ICH with active treatment compared with placebo (55 versus 33; P� 0. 02). n 2012 meta-analysis of 31 RCT trial on statin and risk of intracerebral hemorrhage, there was no significant increase n

Reversing coagulopathies u Check Coag and platelets u Correct thrombocytopenia below 100, some references say below 75. u If on ASA or plavix, should be held and transfused platelets u 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 u If on heparin best reversed with protamine sulfate (1. 0 to 1. 5 mg/1000 U heparin American and Best practice canadian guidelines for stroke management

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

Factor V 11 a § • • 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 American and Best practice canadian guidelines for stroke management

Hematoma Evolution and r. FVIIa 4. 5 ml 5. 8 ml 3. 3 ml r. FVIIa within 4 hours: • Dose dependent attenuation of hematoma expansion • no effect on m. RS at 90 days Mayer et al. NEJM 2005; 352: 777 -85

Treatment of ICHT Intubation n Hyperventilation n Sedation n Steroids: NO role n Osmotic agents n Mannitol n Hypertonic saline n No 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 mm. Hg

ICP control The ICP lowering effect of hyperventilation to a Pa. CO 2 of 25 to 30 mm. Hg 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 American and Best practice canadian guidelines for stroke management

Surgical Indications • Cerebellar bleed: >3 cm, and deteriorating, vs brain stem compression, vs hydrocephalus due to ventricular obstruction • Supratentorial ICH evacuation: Controversial • STICH trial: patients assigned to early (within 24 hr) 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 American and Best practice canadian guidelines for stroke management

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 m. L 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. American and Best practice canadian guidelines for stroke management

Intra-ventricular Hemorrhage n EVD n Intra- ventricular rtpa (CLEAR)

Case 55 F presented with Headache and LOC

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

Factors Affecting Prognosis Volume of hemorrhage n Hematoma growth n Early Neurological deterioration within 48 hr n Oral Anticoaglants n GCS on presentation n Age n Hemorrhage location n Intraventricular hemorrhage n

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 Scale