Disclosures Nothing to disclose Critical Care Management of Acute - PDF document

Disclosures • Nothing to disclose Critical Care Management of Acute Ischemic Stroke Nerissa U. Ko, MD, MAS Associate Professor of Neurology May 31, 2013 Selected slides courtesy of Wade Smith, MD, PhD Overview Pathophysiology • Update on acute revascularization • Time dependent • Focal ischemia is • Acute supportive care different from global ischemia • Blood pressure management • Energy failure-> Ca ++ entry and cell • Post-stroke cerebral edema death • Glutamate toxicity • ICU care after stroke • Apoptosis TIME IS BRAIN 1

Role of Time – IV rtPA Revascularization Therapy with IV tPA Most Recent Pooled Analysis of IV rtPA Trials • Tissue plasminogen activator (t-PA) • NINDS Part 1 – IV t-PA is approved in US for AIS within 3 hours of • NINDS Part 2 symptom onset (OR 1.9; 95% CI 1.2-2.9) • ATLANTIS A – 3 to 4.5 hour window is effective (ECASS-III) • ATLANTIS B • ECASS II • ECASS III • EPITHET Lees et al., Lancet, 2010 ECASS-III Complications with IV tPA • Bleeding • Treatment of tPA-related bleeding – 6.4% vs. 0.6% in clinical trials – no mortality difference – Registry date shows improve – Transfuse blood safety (1.6% bleeding rate) – 10 units cryoprecipitate – Increased risk if not adhering to NINDS trial protocol – 2 units FFP – Earlier treatment associated with – 10 units platelets better outcomes, less – PCC complications – Factor VIIa • Angioedema (1.3-5.1%) – Aminocaproic acid (Amicar) – Swelling of lips, tongue self • 4-5 gm IV, diluted in 250 mL of D5W or NS, limited infuse over 1 hr, followed by 1 g/hr (50 mL/hr) for about 8 hr or until bleeding is controlled – Rx: IV ranitidine, – Tranexamic acid diphenhydramine, • 15 mg/kg IV followed by an infusion of 1 methylprednisolone mg/kg/hr for 5-6 hours • Post-MI myocardial rupture (rare) N Engl J Med. 2008 Sep 25;359(13):1317-29. 2

Revascularization without IV tPA Rescue therapy after IV tPA • IA Lytics – PROACT-II trial supports benefit from IA pro- urokinase; t-PA is used off label • Mechanical Embolectomy – Devices do open vessels and have FDA clearance to open vessels – 2 ongoing, 1 completed study to establish clinical efficacy (MERCI, PENUMBRA, IMS-3) – Stent retriever trials: Solitaire and Trevo (SWIFT, TREVO) show improved efficacy Interventional Management of Stroke (IMS-III) • NIH sponsored, randomized, prospective trial of IV t-PA vs. IV t-PA + endovascular Finish 222 t-PA 656 Outcome: R CT No 2:1 IA t-PA 90-Day hemorrhage EKOS t-PA mRS Stroke IV t-PA MERCI 434 Penumbra Solitaire 58 study centers 6 years Broderick et al , NEJM, March 2013 Broderick et al , NEJM, March 2013 3

Acute stroke interventions Stroke Revascularization 2013 • IV tPA • Embolectomy 0 Proven – Proven efficacy – Stent retrievers better Approved – Better outcome earlier in – Solitaire, Trevo, Merci IV t-PA all subgroups Penumbra all able to recanalize vessels • IA lytics 3 Unproven – No clinical efficacy data – Proven efficacy Thrombectomy • Recue therapy Approved – Unapproved for IA tPA IA pro-UK – New trial data no benefit – Earlier is better, <6 hours – Ongoing trials with new Proven 6 devices Unapproved 8 Time from stroke symptom onset (hr) HTN after Acute Stroke Acute supportive care post stroke • Airway, ventilation, • Cardiac monitoring • Acute HTN is common after acute stroke oxygenation • Current guidelines suggest treatment for SBP> – 24 hours continuous for – Common saturation <96% 220mmHg or DBP > 120 mmHg or if evidence of end- Afib and other rhythms – especially with underlying organ damage – In cryptogenic stroke, cardiac, pulmonary disease • With thrombolytic therapy, goal BP < 180/105 mmHg – Airway obstruction, cardiac event monitors aspiration, atelectasis, • Risk of acute deterioration with aggressive reduction • Hypotension pneumonia of BP – Hypoventilation, • Hypovolemia Cheyne – Stokes • Blood pressure reduction within 24 hours is • Hyperthermia • To intubate or not?? associated with poor outcome – Poor outcome in >50% at • Hypoglycemia – OR 1.89 per 10% decrease (p= 0.047) of poor outcome at 30 days 3 months Neurology 2003; 61:1047-51 4

Blood pressure goals • Optimal blood pressure after acute stroke is controversial • Treat blood pressure cautiously in acute ischemic stroke – t-PA limit <185/110 mmHg – Lower BP by 15% if exceeds 220/120 mmHg – Choice of BP agent is controversial • Labetolol and nicardipine don’t raise ICP Jauch, EC et al. Stroke. January 2013 Ischemic Stroke Penumbra Induced Hypertension • Remains experimental • Consider in specific cases - Hypotension unresponsive to fluid resuscitation - Fluctuating neurological symptoms with hemodynamic changes - Increase BP by 10-20% using pressors and observe for symptom resolution - Potential to incorporate perfusion imaging 5

Induced Hypertension Induced Hypertension is Safe • Rordorf, et al , 1997 For Against • Retrospective safety study in acute stroke Requires ICU care May increase pial- patents and central line pial blood flow access – 33 controls vs. 30 treated with Increase perfusion May cause coronary neosynephrine or gut ischemia to the ischemic Could cause cerebral penumbra – 10/30 treated patients had BP threshold vasoconstriction Is probably safe – No increased cardiac morbidity Evidence for Induced Hypertension Volume expansion/Hemodilution • Koenig, et al. (2006) • Volume expansion with • Treatment of Dextran, hetastarch, hypotension with – 100 patients randomized to either induced HTN or albumin isotonic fluids and standard therapy • No benefit in meta- pressors – Used perfusion MRI to select patients with • Devices to augment BP analysis ischemic penumbra (mismatch DWI/PWI) with counterpulsation • ALIAS: High dose – Non-significant decrease in NINDS scores at in trials only albumin trial stopped discharge in treated group, but with longer LOS, • Vasodilators and • Awaiting trial data ICU time hemodilution not – No difference in adverse events recommended 6

Cerebral Edema Malignant infarct • Severe, life-threatening complication after acute ischemic stroke • Occurs in 10-20% of anterior circulation strokes – Carries a 50-80% mortality when associated with distal carotid or proximal MCA occlusion • Posterior fossa strokes can present with hydrocephalus and brainstem compression – Should be treated with early suboccipital decompression if brainstem is compressed Malignant Cerebral Edema Medical Management • HOB 30 degrees • Typically pattern occurs 3-5 days post-infarct, • Hyperventilation and generally subsides in 2 weeks – Goal pC02 25-30 mmHg • Rarely, edema can occur within 24 hours with – Transient, temporizing measure signs of early herniation • Hyperosmolar therapy • Difficult to predict which patients are at risk – Mannitol – Hypertonic saline – Evidence of >50% MCA infarct within 12 hours • Hypothermia (33-34 – Early sulcal effacement and midline shift degrees Celsius) – Reperfusion injury after thrombolysis • No role for corticosteroids – Perfusion maps potentially helpful; DEFUSE study 7

Osmolar Therapy • Mannitol – Typically bolus over 20 min (0.25-0.5 g/kg every 4-6 hours) – Monitor for hypotension and hypovolemia – Can precipitate renal failure – Less effective at serum osms >320 mmol/dl • Hypertonic saline – Infusion of 3% NaCl to maintain serum sodium gradient – Bolus of 23.4% NaCl over 20 minutes very effective – Less side effects of hypotension, renal failure European Pooled Trial Hemicraniectomy in Ischemic Stroke • Prospective pooled analysis of 3 trials of • Decompressive surgery to decrease mass decompressive surgery in malignant MCA effect and tissue shift after ischemia is infarction controversial. • DECIMAL, DESTINY, HAMLET • Evidence of benefit in patient populations – Age 18-60 – Treatment initiated within 48 hrs of stroke onset such as trauma, SDH, mass lesions and – Randomized to surgery or conservative Rx posterior fossa strokes – N=93 patients • Meta-analysis showed reduced mortality and – Reduced mortality 78-29% improved outcomes with hemicraniectomy for hemispheric strokes Vahedi et al. Lancet Neurology March 2007 8

Hemicraniectomy Results Alive but unable to walk (NNT=2) Alive, disabled but able to walk (NNT=4) Side of stroke (dominant hemisphere) Did not matter Vahedi et al. Lancet Neurology March 2007 Vahedi et al. Lancet Neurology March 2007 Antithrombotic Therapy for Stroke Antithrombotic agents • Avoid routine use of IV heparin, IIb/IIIa agents • Aspirin alone is the only proven strategy within the first 24-48 hours • Dural sinus thrombosis and arterial dissection may specifically benefit from heparin Neurology, 2001; 57: S53-57 9