Normal flow, normal function 50 Low flow, raised O2 extraction, normal function CBF (ml/100g brain) 20 Synaptic transmission failure 10 Membrane pump failure 0 3 4 5 1 2 Time in hours
Ischaemia - 02 ê glucose ê é lactate Anoxic depolarisation Ca2+ ié Hi é Free Fe2+ Glutamate Lipolysis NO synthase Proteolysis NA, Dopamine Free radicals Ischaemic Brain Injury
Aim of Rx: Ischemic Stroke Reperfusion Thrombolysis Mechanical disruption of clot Reducing the size of infarct Antiplatelate Anticoagulant Neuro-protection Blood pressure control Treat associated complication Raised ICT Seizure
Thrombolysis in acute stroke Within 3-4.5 hour of Stroke No occlusion Stop Medium Vessel Large Vessel IV rTPA/URK IA rTPA/URK C-D/ D-P mismatch
Challenge of thrombolysis Lack of awareness: Patient Physician Out of scope Operational issue Emergency team Imaging team Failure of medical thrombolysis Re-closure of opened vessel: (Stenting) Reperfusion injury with toxic edema and hemorrhage
Overcoming challange Education Patient Physician Alternative approach in failed cases Mechanical disruption of clot: Primary angioplasty Transcranialdoppler and thrombolysis Surgical emergency endarterectomy Stenting to prevent reclosure
Blood pressure control Systolic BP < 220 or diastolic < 120 Observe unless other end-organ involvement Systolic BP > 220 or diastolic >120 Labetalol 10-20 mg IV over 1-2 mins. May repeat or double every 10 mins. (300 mg/d) Diastolic BP > 140 Nitroprusside 0.5mcg/kg/min IV infusion *Aim for 10-15% reduction of BP Systolic BP > 185 or diastolic > 110 For thrombolysis Labetalol 10-20 mg IV over 1-2 mins. May repeat x 1 60 160 Mean systemic BP
Aspirin in Acute Stroke Aspirin 325mg Clopidogrel 75-150mg if Aspirin CI Early recurrent ischemic stroke – 7 fewer per 1,000 treated (p< 0.0001) Death from any cause – 4 fewer per 1,000 treated (p=0.05) Death or early recurrence of non-fatal stroke – 9 fewer per 1,000 treated (p=0.001) Death or dependency at discharge or six months – 13 fewer per 1,000 treated (p=0.007) Hazard : Hemorrhagic stroke or transformation – 2 more per 1,000 in ASA treated (p=0.06) Bath, 2001b [A]; Chinese Acute Stroke Trial Collaborative Group, 1997 [A]; International Stroke Trial Collaborative Group, 1997 [A]; Sandercock, 1993 [M]).
Anticoagulant in Acute Stroke Early use (<3Hr) may reduce mortality and morbidity. Hemorrhagic transformation is high Arterial dissection Cardioembolic infarct with or without AF Immediate for small infarct if re-embolization risk is high Delayed 2 weeks for all cases Heparin - 1000 units/hr. PTT 1.5 avoid bolus Enaoxaparin – 40mg SC BD Low dose Enoxaparin 40mg SC OD prophylactic for DVT
Other measures Statins Use after 2 days of onset (AHA) Continue in those already taking (NHS) Neuroprotection Citicolin Magnesium
Spontaneous Intra-cerebral Hemorrhage
This 66-year-old white man with a baseline GCS score of 14 and NIH Stroke Scale score of 20 had a putaminalhemorrhage with a baseline ICH volume of 10 mL (top row)
The ICH volume on the 1-hour CT was 27 mL (bottom row). However, the 17-mL increase in ICH volume was not accompanied by any change in the 1-hour GCS (14) and NIH Stroke Scale (20) scores.
Hematoma volume 30d outcome (Joseph P. Broderick et al Stroke 1993;24:987-993)
Approach to Treatment of ICH Stopping or slowing the initial bleeding Factor VIIa Blood pressure control Reducing raised ICT due to Hematoma and Edema Evacuation of hematoma Osmotherapy Neuroprotection Control of Seizure and other associated complication
A. Factor VIIa Trial Useful in Hemophilia with Ab to factor VII or IX Produce clotting by stimulating coagulation cascade in normal Used in cased of ICH secondary to coagulopathy There is mild reduction in progression of hematoma, morbidity and mortality (Phase II, III trial) INR may return to normal transiently it require repeated dose Routine use in Primary ICH remains investigational
B. Blood Pressure control Hypertension is common during early states of ICH -> Expansion, Peri-hematoma edema and re-bleeding A systolic BP above 140 to 150 mm Hg within 12 hours of ICH is associated with more than double the risk of subsequent death or dependency. Association of low BP and deterioration is not consistent like ischemic stroke. Blood pressure Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH- I) INTensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT- I)
Recommendation: AHA 2010 In patients presenting with a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe Class IIa; Level of Evidence: B
Raised ICT The Monro-Kellie doctrine
Problem secondary to raised ICT Early hematoma expansion and secondary edema-induced brain compression and consequent neuronal death; Cytotoxic (intracellular) and vasogenic (extracellular) edema resulting from disruption of the blood–brain barrier; Reductions in cerebral perfusion pressure (CPP) from mass effect and raised intracranial pressure (ICP); Brain herniation
Approach to raised ICT Head end elevation Surgical evacuation of hematoma Osmotherapy Hyperventilation Analgesia and sedation Neuromuscular block Barbiturate coma Hypothermia Corticosteroid CSF drainage Defroxamin
Head-of-Bed Elevation Elevation of the head of the bed to 30° improves jugular venous outflow and lowers ICP. The head should be midline, and head turning to either side should be avoided. In patients who are hypovolemic, elevation of the head of the bed may be associated with a fall in blood pressure and an overall fall in CPP.
Principals of Osmo-therapy Brain volume falls as long as there is an osmotic gradient between blood and brain. Short lived action few hours. Normal brain shrink (White/ Gray) Rebound edema. Dose not clear: 10 mOsm/L change in osmolality may be effective Chronic use not recommended as brain adapt
Mannitol Wise and Chater in 1962 Cleared from brain and CSF due to large molecular wt (182Dalton), less rebound phenomenon. Rebound phenomenon with increasing dose to sustain hyperosmolality of brain, as serum osmolality falls Dose: 1g/kg increases serum osmolality 20-30 mOsm/L for 3-4 hours. Higher dose 1.5-2gm/kg lower CSF pressure for longer time with increased rebound phenomenon. Lower dose 0.5gm/kg has less rebound
Mannitol Use in Acute Stroke Case Fatality at 30 Days and 1 Year In a tricenter, prospective study, 809 patient with ICH within 72 hours were analyzed 30-day and 1-year case fatality with respect to mannitol treatment in 2/3rd cases No recommendations can be made on the use of mannitol in acute stroke. Stroke. 2003;34:1730-1735.
Mannitol in ICH Randomized, controlled, double-blind study. Mannitol 20% 100ml q6h within 6 days of ictus for 5 days, tapered in next 2 days Mannitol did not seem to be beneficial in patients with ICH J Neurol Sci. 2005 Jul 15;234(1-2):41-5.
Effect of single mannitol bolus in intracerebral hemorrhage CT scan >3cm midline shift in ICH Randomized with bolus dose of Mannitol /Saline. Superior sagittal sinus to pontomesencephalic junction (SSS-PMJ) distance and edema hematoma complex were measured. Mannitol led to transient clinical improvement in five patients without significant reduction in superior sagittal sinus to pontomesencephalic junction (SSS-PMJ) distance at 30 and 60 min. U. K. Misra et al Department of Neurology, Sanjay Ghandi PGIMS, Lucknow, IndiaEur J Neurol. 2007 Oct;14(10):1118-23. Epub 2007 Aug 28.
Effect of mannitol on early enlargement of hematoma following hypertensive cerebral hemorrhage Hypertensive cerebral hemorrhage cases were randomized Group A 36 – Mannitol Group B 35 – furosemide Two follow-up CT were done Result: Enlargement of hematoma Group A : 33 3% patients(12 cases) Group B: 17 1% patients(6 cases) The inapt use of mannitol may be one reason of the early enlargement of hematoma following hypertensive cerebral hemorrhage Wang Minzhong,PangZaiying,FengYabo,et al
Hypertonic Saline Used in head injury and when Mannitol or Hyperventilation failed No trial on stroke patient Abrupt change in serum osmolality may leads Coma, Seizure and Subdural hematoma Pontine myelinolysis Volume expansion Cardiac failure Altered coagulation parameters -> bleeding Prolongation of PT, TT Decreased platelet aggregation Rebound phenomenon
Recommendation: Raised ICT Conservative An elevation of the head of the bed Analgesia and sedation Aggressive therapies Osmotic diuretics (mannitol and hypertonic saline solution), Drainage of CSF via ventricular catheter, Neuromuscular blockade, Hyperventilation, generally require concomitant monitoring of ICP and blood pressure with a goal to maintain CPP >70 mm Hg Class IIa, Level of Evidence B
Seizure and Antiepileptic drugs Incidence at onset -> 2 weeks: 3-17% Electrographic seizure 28-31% (on AET) One study prophylactic AE reduce clinical Sz. after Lobar hematoma Prospective population based studies did not show clinical Sz and worsened neurological outcome or mortality. Subclinical Sz.: one study showed prophylactic PHY increased disability and death at 90 days.
Recommendation: Seizure control Clinical seizures should be treated with antiepileptic drugs Class I; Level of Evidence: A Continuous EEG monitoring in patients with depressed mental status out of proportion to the degree of brain injury Class IIa; Level of Evidence: B Patients with a change in mental status who are found to have electrographic seizures on EEG should be treated with antiepileptic drugs Class I; Level of Evidence: C Prophylactic anticonvulsant medication should not be used Class III; Level of Evidence:B
Summary - ICH Rx Blood pressure control remains the mainstay of management in hemorrhagic stroke Osmotherapy has doubtful role and routine use is not indicated in minor bleed. Clinical and subclinical seizure with EEG abnormality should be treated. Surgical evacuation of hematoma and Supportive and critical care of patient during acute state is most important to reduce morbidity and mortality