Management OF INTRACEREBRAL HEMORRHAGE Navaz Karanjia, MD Director of Neurocritical Care University of California – San Diego

Intracerebral Hemorrhage

Intracerebral Hemorrhage All my management, as well as my service’s, should follow the 2010 aha guidelines for ich, and so should my residents, because I wrote a set of UCSD guidelines based off

Intracerebral Hemorrhage

Neurocritical Care Management of Intracerebral Hemorrhage Epidemiology 10-15% of all strokes, 50-70,000 cases/yr in US Presentation Headache, neurologic deficit Outcomes 40% 30-day mortality Reduced by 17% by an NCCU/neurointensivist 20% independent at 6 months Improves by 21% by an NCCU/neurointensivist Mirski M, Chang CW, and Cowan R. J Nsurg Anesth 2001; 13(2): 83-92. Lancet Neurol. 2010 Feb;9(2):167-76. doi: 10.1016/S1474-4422(09)70340-0

Intracerebral Hemorrhage Causes of ICH

Intracerebral Hemorrhage Common locations for hypertensive ICH The most common cause of ich is hypertension causing atherosclerosis and weakening of small arterioles in the white matter. Most common places are… how will these present? Thalamus Cerebellum Pons Basal Ganglia

Intracerebral Hemorrhage Clinical course and complications Tissue dissection, displacement, increased ICP (immediate) Hematoma expansion (immediate ->36h) Hydrocephalus Neurohemoinflammation/Cerebral edema (day 2-5) Seizures Central fever People usually survive the initial hemorrhage, but the reason why 40% of patients end up dead at 30 days is because of the complications over the first hours and weeks, from the immediate issues of ICP crisis hematoma expansion and hydrocephalus, to the cerebral edema, seizures, and central fever that set in a couple days later and try to kill off all this other healthy tissue that surrounds the hematoma.

Intracerebral Hemorrhage Hematoma expansion 72% have some hematoma expansion over 24h 38% have clinically significant expansion within 24h Within 1 hr in 26% of cases Worsens outcome

The first thing that can kill your patient is

Neurocritical Care Management of Intracerebral Hemorrhage Preventing hematoma expansion (INTERACT, ATACH) IMMEDIATE BP control reduces expansion 30% Target SBP 140-150 with nicardipine drip or labetalol/hydralazine IVP WITHIN 10 MINUTES IMMEDIATE coagulopathy reversal FFP, PCC (KCentra) within 30 min Recheck coags 15 min post PCC Platelets if <100,000 or TEG abnl NOT factor VII (FAST trial) Time to reversal is being tracked How do we prevent this? With immediate BP control, which reduces expansion by 30% Another thing we do immediately is reverse coagulopathy by giving FFP or PCC immediately. This is so important that time to reversal is being tracked by the joint commission

UCSD Reversal Protocol for Spontaneous Intracerebral Hemorrhage with INR > 1.4 STAT Labs: PT/INR, PTT, fibrinogen, platelets, CBC, Type and Screen, troponin If crash craniotomy considered, type and cross 2U PRBC Give vitamin K 10mg IV stat; if IV not available, give 10mg PO Transfuse 2U FFP stat over 30 min. If type&screen will take >30 min and INR>2, transfuse 2U uncrossmatched FFP. If pt cannot tolerate FFP due to volume overload, use PCC+Factor 7 20-40mcg/kg (1-3 mg) INR 1.4 – 2.0 INR > 2.0  History of thrombotic event in past 6 wks? (DVT, PE, trauma, ischemic stroke, ACS, mesenteric ischemia, etc) Major surgery within 6 weeks? Heparin induced thrombocytopenia (HIT)? Can patient tolerate more FFP (volume status)? YES NO YES NO FFP Pathway PCC (Profilnine) Pathway Immediately give 2 more units FFP Repeat coags upon completion of infusion If INR still >1.4, 2 more units FFP If still > 1.4, consider PCC and consult hematology Once INR ≤1.4, repeat INR q4-6 hrs for 24-48 hrs INR 2-4: infuse 25 units/kg body weight* Profilnine over 5 min, not to exceed 2ml/min INR >4: infuse 40 units/kg body weight* Profilnine over 10 minutes, not to exceed 2ml/min Repeat INR 15 minutes after infusion complete. If INR not at target, repeat q15 min x2 until INR at target. Once INR ≤1.4, repeat INR every 6 hrs for 24 hrs. If INR > 145, give another 10mg vitamin K IV/PO and consider 2 more units FFP. If INR does not reach target in 45 minutes, consider Factor 7, 20-40 mcg/kg (1-3mg) IV x 1 Check the following labs at 1 hr and q6 hrs after completion of PCC infusion: PT/INR, EKG and Cardiac enzymes, Fibrinogen * in obese patients, base dose on a maximum weight of ideal body weight + 20% *** At 24 hrs, repeat dose of Vitamin K 10 mg IV/PO

IF ON RIVAROXABAN or APIXABAN (factor Xa inhibitor) UCSD Reversal Protocol for Spontaneous Intracerebral Hemorrhage on Dabigatran, Rivaraoxaban, or Apixaban STAT labs: PT/INR, fibrinogen, platelets, CBC, PTT, TT, anti-Xa level , Type & Screen If crash craniotomy considered, type and cross 2U PRBC IF ON DABIGATRAN (direct thrombin inhibitor ) and TT prolonged IF ON RIVAROXABAN or APIXABAN (factor Xa inhibitor) and PT/INR is prolonged or anti-Xa level elevated IF ingestion within 2 hrs, give one dose activated charcoal orally infuse 25 units/kg (+/- 10%) body weight* PCC (Profilnine) over 5 minutes, not to exceed 2ml/min Transfuse 2 units FFP STAT. If type and screen will take >30 min, transfuse 2 units uncrossmatched FFP. Stat labs at 15 min and q6 hours after completion of PCC infusion: PT/INR, TT, EKG, cardiac enzymes, fibrinogen, anti-Xa level. If TT or PT/INR is still prolonged AND patient still bleeding/extreme risk of hematoma expansion, consider repeating Profilnine dose or giving Factor 7, 20-40mcg/kg (1-3mg) IV x1 Emergent dialysis may be considered in certain circumstances (renal failure, overdose); ~ 65% removed by hemodialysis Dabigatran t ½ = 14 hrs (up to 34 hrs in severe renal impairment) Rivaroxaban and Apixaban are NOT dialyzable Rivaroxaban t 1/2 = 9 hrs (longer in renal impairment) Apixaban t ½ = 12 hrs (longer in renal impairment) * in obese patients, use maximum weight of ideal body weight + 20%

Neurocritical Care Management of Intracerebral Hemorrhage Acute obstructive hydrocephalus occurs in 50-70% of IVH patients treat with emergent EVD Intraventricular tPA for IVH clears IVH faster (11.4->2.6 days), likely reduces hydrocephalus/need for VP shunt, ? mortality/outcomes (CLEAR-IVH) Hydro can happen immediately or within the first few hours after ich, as the blood settles into the 3rd or 4th ventricle, blocking off the flow of csf. The backup of csf can cause enough increase in icp to make you herniate within an hour, if you don’t pop in the evd. Huttner HB, Tognoni E et al. Eur J Neurol. 2008;15(4):342.

Intracerebral Hemorrhage Neurohemoinflammation/cerebral edema Peaks days 2-5 Exacerbated by fever and seizure Medical cerebral edema treatment ((hypertonic saline, normothermia, seizure control, ventilation control) Surgical/endoscopic clot removal It peaks between days 2-5 so for those of you that have seen me talk to families about this, I always say, it’s going to get a little worse before it gets better, because the swelling sets in around 48 hrs. This is caused by the concept of neurohemoinflammation, which is the basic concept that blood breakdown products are very irritating, causes bbb breakdown

Neurocritical Care Management of Intracerebral Hemorrhage Surgical clot removal (MISTIE II, STICH II trials) Endoscopic for deep clots Improves good outcome 20% 34% Open for all superficial clots Reduces mortality (STICH II) The next thing that can kill your patient is the cerebral edema, and so the brain code protocol that I showed you is frequently used on ich patients. Another option to help reduce edema and midline shift is surgical clot removal.

Neurocritical Care Management of Intracerebral Hemorrhage MISTIE II With endoscopic clot removal you get many more asymptomatic patients and Modified rankin 1 patients Hanley, D et al. Mistie II Trial Results: 365 day outcome and cost-benefit. ISC 2013 Late Breaking News http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_449055.pdf

Neurocritical Care Management of Intracerebral Hemorrhage Seizure control 33% of altered ICH patients have seizures, most are nonconvulsive Seizures worsen ICP, midline shift All altered ICH pts should receive continuous EEG monitoring (Class I, LOE B ) 2012 Neurocritical Care Society Guidelines: Indications for Continuous EEG Monitoring Claassen et al. Anesthesia Analg. Vol. 109, No. 2, August 2009

Neurocritical Care Management of Intracerebral Hemorrhage Seizures after ICH leads to worsening midline shift Blood oxygenation drops to ischemic levels during seizures Vespa et al Neurology 2003

Neurocritical Care Management of Intracerebral Hemorrhage Seizures after ICH leads to worsening midline shift Lactate/pyruvate ratios by microdialysis demonstrates neurons are becoming ischemic during seizures Vespa et al Neurology 2003

Neurocritical Care Management of Intracerebral Hemorrhage Seizures after ICH leads to worsening midline shift And midline shift worsens by on average half a centimeter during a seizure, the pt may die by way of herniation before they live long enough to have detectable brain atrophy. Vespa et al Neurology 2003

Intracerebral Hemorrhage Antiepileptics are indicated ONLY if the patient demonstrates evidence of seizure clinically or on EEG (prophylactic AED’s worsen outcome, OR mRS>3 = 9.8). Class I, LOE B AED PROPHYLAXIS? Naidech et al, Stroke 2009

Intracerebral Hemorrhage Central fever Occurs in 70% of patients Increases cerebral metabolic rate, ICP, and midline shift Normothermia should be maintained and fever treated aggressively, using antipyretics and intravascular/surface cooling devices if needed (Class I, LOE B recommendation)

Neurocritical Care Management of Intracerebral Hemorrhage Normothermia, glycemic control, dysphagia screening Lancet 2011: For all hemorrhagic and ischemic stroke patients, implementation of an RN protocol to treat any temp≥37.5, glycemic control, dysphagia screening decreases death/dependence 58% -> 42%, NNT 6.4

Intracerebral Hemorrhage

Neurocritical Care Management of Intracerebral Hemorrhage To emphasize that point, the patient on the right, here he is 2 months after he came into the hospital with 2 blown pupils and posturing, we unherniated him medically, he went for a clot evacutaion, and he left the hospital comatose, but we knew he was going to come back because the bleed hadn’t been that large, it was just in an unfortunate place, and we had gotten him back quickly at every step of the way. This was his first post discharge visit, and soon after that he went to acute rehab, started walking. He’s now living at home hanging out with his kids. The pt on the left had a 100cc L parieto-occipital ich, required 1 month of being hypothermized and in prpofol coma to control his icp, and now he is walking, talking, taking care of his kids, and walking a mile every day, and going back to work next month.