General measures of acute stroke management

1. General measures of acute stroke management Apostolos Ι. Hatzitolios Associate Professor of Internal Medicine 1st Propedeutic Department of Internal Medicine Department of Vascular Diseases and Hypertension Aristotle University of Thessaloniki, AHEPA Hospital Thessaloniki, Central Macedonia, HELLAS

2. Emerging therapies for acute stroke • Main target is the early intervention and preservation of penumbra within a short therapeutic interval before necrosis of ischemic area occurs. New drugs are tested on this direction. • The development of specific therapeutic procedures is an important research priority. • Advances in this field aim mainly toenlarge the capability of thrombolysis use, despite limitations (since recovery may be achieved with a narrow time window of ~ 3-4.5 h). • Investigation interest is focusingon the: • use of neuroprotective agents leading to expansion of the “therapeutic window” (over 3 h), • immediate MRI with advanced sequences to refine the patient selection and reveal the exact size of infarct, • use of next-generation thgrombolytics (plasminogen activators and glycoprotein IIb/ IIIa inhibitors), • use of agents to avoid hemorrhagic transformation of large infarcts, • endovascular approaches to thrombolysis and thrombectomy, and • adjuvant use of ultrasound. • There is still also no proven therapy for intracerebral hemorrhage, although early results with recombinant activated factor VII look very promising.

3. General measures of acute stroke management Treatment strategies aiming mainly at stabilizing the critically ill patient in order to control systemic problems that may impair stroke recovery, become of the greatest clinical importance • Cardiac/respiratory care • Fluid and electrolyte balance • Blood pressure control • Glucose metabolism • Body temperature • Dysphagia and nutrition

4. Cardiac care • Cardiac complications more frequent in ICH and SAH than in ischemic stroke • 15-40% of stroke patients may experience - AMI - Congestive heart failure - Arrhythmias, particularly AF - Sudden death • There is a more significant correlation between cardiac complications and infarcts of the insular cortex

5. Respiratory care • Adequate oxygenation is important to preserve the penumbra. • Most common causes of hypoxia in stroke: - Preexisting pulmonary diseases - Airway obstruction due to cranial nerves paresis causing oropharyngeal muscular hypotonia or vomiting leading to aspiration (brainstem stroke, reduced vigilance) - Hypoventilation due to: Large hemispheric infarct or Brainstem infarct or hemorrhage Heart failure Pulmonary embolism Status epilepticus

6. Cardiac / respiratory care & Electrolyte / fluid homeostasis • Continuous cardiac monitoring in the first 48 hours • Oxygenation monitoring and Oxygen administration in case of hypoxemia • Monitoring and correction of electrolyte and fluid disturbance • Hypotonic solutions are contraindicated due to the risk of brain oedema, caused by the reduced plasma osmolality

7. Management of Hypertension in stroke patients In hypertension, cerebral vessels adjust to elevated BP by wall thickening, increasedresistance andshift of blood flow autoregulationat higher BP level. The problem is greater in older patients because ofincreasedvascular resistance and decreased cerebral blood flow So, great and abrupt BP decrease results in blood flow disturbance, cerebral ischemia and cognitive function deterioration

8. Because of cerebral autoregulation abolishment in ischemic stroke area, blood flow is directly depended on systemic BP 220 200 180 160 140 Mean BPmm Hg 120 100 80 60 40 1st day 2 hours later 2nd day transfer • Therefore, BP increases in acute stroke as response to stress due to increased levels ofcatecholamines and cortisol, in order to maintain blood flow in the critical ischemic penumbra, while • BP decreases automatically the next days

9. Blood pressure control & Management of hypotension • Target should be the progressively decrease of BP, < 15% /day, without orthostatic phenomena and hypotension, so that gradually more BP decrease becomes tolerable. • Routine BP lowering is not recommended, except for extremely elevated values which are lower for hemorrhagic strokes (>200-220 SBP or 120 DBP for ischemic, >180/105 for hemorrhagic stroke) • Immediate antihypertensive therapy for more moderate hypertension is recommended in heart failure, aortic dissection, acute MI or acute renal failure co-existence and in case of thrombolysis (avoid SBP above 180mmHg), but should also be applied cautiously. • Generally, recommendedtarget BP in patients - with prior hypertension: 180/100-105mmHg - without prior hypertension: 160-180/100mmHg 4. Hypotension should be also avoided and treated (SBP < 120 mmHg) since hypovolemia could cause neurological deterioration

10. Narrow pathophysiological relationship between Hyperglycemia and Neuronal damage Brain ishemia Hyperglycemia Anaerobic metabolism - glycolysis Lacticproduction / lactic acidocis ( Η+) IntracellularCa+2 Free radicals Endonucleases Glutamic Mitochondrial damage intracellular oedema Irreversible neuron cell damage

11. Management of hyperglycemia & hypoglycemia • Hyperglycemia, but also hypoglycemia should be treated because they might worsen the ischemic damage and attenuate neuron metabolism and restoration respectively • Monitoring of serum glucose levels and treatment with insulin titration is recommended • Restoration to normal has to be gradual, especially in diabetics, in order to avoid intracellular neuron oedema • Immediate correction of hypoglycemia (i.v. dextrose) is also recommended

12. Temperature Dysphagia & Feeding • Experimentally fever increases infarct size • Body temperature increases in up to 50% of patients consequent to a severe brain infarct as an acute phase response • High body temperature may favor stroke progression and long term bad outcome • Treatment of body temperature >37.5C and search of possible infection (site and etiology) is recommended • Dysphagia is present in up to 50% of patients • Predictor of poor prognosis enhancing the risk for aspiration and pneumonia, dehydration and malnutrition • Early commencement of nasogastric feeding, within 48 hours, is recommended in stroke patients with impaired swallowing while PEG (Percutaneous endoscopic gastrostomy) feeding after the first 2 weeks

13. Prevention of acute stroke complications • Most frequent complications of acute stroke are - Bladder dysfunction and urinary tract infections - Bronchopneumonia - Decubital ulcers - Seizures - Deep vein thrombosis and pulmonary embolism • Low molecular weight heparin (or low dose subcutaneous heparin) should be considered for patients at high risk of DVT or PE. Anticoagulant therapy may add a further benefit during stroke in-evolution by preventing clot expansion. • Incidence of venous thromboembolism may be also reduced through early re-hydration and mobilization, as well as compression stockings • Regarding oxidative stress and it’s management, the favorable action of antioxidants like vitamin E, for the treatment of is controversial

14. Surgical or electrophysiological intervention & anticoagulation in patients with high embolic risk : Atrial fibrillation Valvular disease Dilated cardiomyopathy Patent foramen ovale Checking for stenosis in the carotids (common/internal) with Triplex Echo and CTA orMRA Symptomatic carotid stenosis > 70%:requiresendarterectomy (at centers with perioperative mortality <6%) 50-70%: (benefit of intervention is statistically significant) endarterectomy is also considered Asymptomatic stenosis > 60%, Intervention is also discussed, since risk for strokeis also significant (annual 2%, expected reduction 1% ) at centers with low perioperative mortality rate (<3%) Angioplasty ± stenting indicated only in patients with symptomatic stenosis and high perioperative endarterectomy risk. Prevention of stroke reccurence Heart disease Carotid disease

15. High co-existence percentage of CHD, CeVD & PADTotal risk management with common preventive measures Coronary Heart disease Cerebrovascular disease 13% 15% 33% 8% 5% 14% Peripheral artery disease 12% Stroke = Clinicalmanifestation of Global Vascular Disease Atherothrombotic manifestation from a vascular areashould alarm forthe existence of vascular diseasealso in another area

16. Total Risk: Secondary Prevention ofCardio- Cerebro-Vascular & Renal Disease • Lifestyle Changes • Hypertension (< 130/80mmHg) • Dyslipidemia (LDL< 100mg/dl) • Diabetes ( HbA1c <7%) • Antiplatelets/anticoagulants Atherosclerosis progression as well as oxidative stress induction should be inhibited by use of agents exerting endothelium protection, inflammation decrease, stabilization of atherosclerotic plaque and - in case of stroke - possible neuroprotection from ischemia (RAS inhibitors, statins, vitamin E?)

17. International guidelines for stroke management& Secondary prevention after stroke/TIA • European Stroke Organization - ESO (formerly known as EUSI - European Stroke Initiative) Recommendations for stroke management Cerebrovasc Dis 2003;16(4):311-37 (update 200 12th EUSI Stroke Summer School, Lausanne 2008) • American Stroke Association Guidelines for the prevention of stroke in patients with ischemic stroke or transientischemic attackStroke 2006;37:577-617

18. Thank you for your attention!