Intensive Care Management of Ischemic and Hemorrhagic Stroke

1. Intensive Care Management of Ischemic and Hemorrhagic Stroke Northern Michigan Hospital�s Stroke Care: The Pursuit of Clinical Excellence Workshop 21 September 2007 William M. Coplin, MD, FCCM Associate Professor of Neurology & Neurological Surgery Chief of Neurology and Medical Director of Neurotrauma & Critical Care Detroit Receiving Hospital, Detroit, Michigan wcoplin@med.wayne.edu

2. Usual Disclosures/Disclaimers NIH/NINDS ACCP SCCM Astellas Pharma US At one time or another I have prescribed the drugs manufactured by most of the companies producing drugs to alter blood pressure and received support from one of them PDL BioPharma

3. Topics Pulmonary Care: Breathe Deep Blood Pressure: Why All the Confusion? Electrolytes: Spice of Life Antibiotics: What bugs are in your home? Seizures: No Shaking Necessary VTE Prophylaxis: Avoiding the Clots Agitation: Wake up Swinging Outcomes: Nihilism or Hopefulness

4.  Breathe Deep

5. Ventilation and Oxygenation Goals Optimize cerebral oxygenation Brain consumes 15% of cardiac output and 20% of available O2 Hypoxia associated with poor outcome Data supporting oxygen toxicity in critically ill patient not compelling Hyperventilation May treat ICP elevations at the cost of CBF Hypoventilation Shifts Hgb-O2 saturation curve, facilitating O2 delivery and improving PbtO2 Is there a role for permissive hypercarbia?

6. Effective Airway Management Maintain or establish patent airway early to prevent hypoxemia Tracheostomy? Does it facilitate secretion removal, airway management, disposition? Safety: PEEP < 8, FiO2 < 50%, able to lie flat x 30 min Extubation requirements Can patient oxygenate, ventilate and protect airway? Do not have to be awake following commands

7. Pneumonia Risk LOC and EtOH use increase risk of aspiration Risk 26-42% Risk factors include - Staph aureus nasal carriage, aspiration, barbiturate use Lower PaO2/FiO2 ratio, more febrile days, more frequent hypotension, increased ICP Coplin W et al. Am J Respir Crit Care Med 2000;161:1530-6 Bronchard R et al. Anesthesiology 2004;100:234-9 Goals of care Eliminate risk factors - �vent bundles,� oral care, hygiene Early diagnosis Early and appropriate antibiotic therapy

8.  Blood Pressure: Why All The Confusion?

9. Randomized Controlled Trials of BP Management After Stroke/ICH (none)

10. Evaluation of Nicardipine and Labetalol for Acute Blood Pressure Control Following Stroke Presented at 2006 SCCM Annual Congress

11. Blood Pressure Reduction

12. Specific Outcomes

13. Time to Goal in ICH Patients Nicardipine vs. labetalol 5.1 times as many patients reached goal within 1 hr with nicardipine as did with labetalol 56% vs 11% p = 0.02 For comparison: Nicardipine 14 min to response with 1.5 adjustments SNP 30.4 min to response with 5.1 adjustments Halpern NA, et al. Crit Care Med. 1992;20:1637-1643 Nicardipine11.5 min to response IV Nicardipine Study Group. Chest. 1991;99:393-398

14. BP Variability

15. Randomization Scheme

16.  Spice of Life

17. Electrolytes Glucose Sodium Determination of volume status is critical Potassium May transiently increase with tissue injury or underperfusion Increased filtered/excreted K+ with elevated aldosterone may cause overall K+ depletion Magnesium Potential neuroprotection Ongoing study

18. Glucose Control Early hyperglycemia associated with poor outcomes after stroke Conventional vs. intensive glucose control in ischemic stroke and ICH patients Insufficient evidence In TBI, patients with intensive therapy had reduced ICP, less frequent seizures, higher KPS @ 6 and 12 months Van den Berghe et al. Neurology. 20005;64:1348-53

19. Water Balance Hyponatremia Overall incidence of 7% in ICH and 4.5% in AIS Kusuda K. et al. 1989 Iatrogenic Syndrome of Inappropriate ADH (SIADH) Cerebral Salt Wasting (CSW) Misdiagnosis may exacerbate problem Hypernatremia Iatrogenic Diabetes Insipidus (DI)

21. Diabetes Insipidus - Central No problem�if free access to water If not�hypernatremic volume contraction Treatment Replete free water Maintain euvolemia - isotonic fluids Administer vasopressin or desmopressin Avoid offending medications

22. Etiology of Hyponatremia SIADH Increased release of ADH through direct injury, hypercapnia, hypoxia, pain, medication effects SIADH Increased release of atrial naturietic factor Renal Na+ loss

23. Hyponatremia: SIADH vs CSW

24. Hyponatremia: General Principles Determine severity of symptoms Seizures Abrupt change in LOC Worsening edema or ICP Determine rate of development May be treated more rapidly if acute, rather than chronic Assess volume status

25. Hyponatremia: Initial Interventions Eliminate sources of free water Check medication solutions If developed rapidly (> 0.5 mEq/L/hr) May correct @ 1-2 mEq/L/hr to achieve Na+ 128-130 Complete normalization over 1-2 days after initial correction Maximum correction ~ 20 mEq/L in 1st 48 hrs

26. SIADH Treatment Acute Fluid restriction? Avoid hypotonic fluids Supplementation: saline Furosemide to enhance free water excretion? Follow K+ closely Conivaptan to enhance free water excretion? Chronic Demeclocycline 300 mg q 6 hrs Fludrocortisone 0.1-0.2-0.3 mg/day

27. CSW Treatment Hydration Saline Fluid restriction will worsen condition

29. Other Important Equations knowledge = power time = money power = work / time ? knowledge = work / money Solving for money, money = work / knowledge Thus money approaches 8 as knowledge approaches 0, regardless of the work done Or, the less you know, the more you make

30.  What bugs are in your home?

31. Rational Antibiotic Therapy Every ICU has its own biogram -- ask! Organ and Tissue Donation Policy Brain Death Protocols Donation after Cardiac Death Policy No evidence to support empiric antibiotics If clinical indications of infection, culture then start antibiotics based on biogram Believe your cultures If negative -- stop antibiotics If positive -- narrow spectrum of antibiotics Duration of therapy?

32. ID Issues

33. Suggested Empiric Regimens

34.  No Shaking Necessary

35. Incidence of Seizuresafter Ischemic Stroke 2-6% incidence of seizure after stroke 22-27% as status epilepticus Lobar strokes more likely than others? No relation to stroke severity (NIHSS) Seizures not predictive of outcome No influence on mortality

36. Incidence of Seizures afterIntracerebral Hemorrhage 11.2% (n = 14) had documented seizures before or while in the ED Demographic and presenting clinical features similar between the seizure and non-seizure groups

37. CT Characteristics

38. Clinical Features

39. Outcome Having a seizure unrelated to presenting and discharge GCS and GOS Seizures unrelated to mortality 12% (11/91) of survivors 9% (3/34) of those dying before discharge

40. Antiseizure Prophylaxis Data insufficient to support recommendation No AAN practice parameter Expectant management

41. Concerns re: Prophylaxis Side effects Cognitive impairment Myelosuppression Liver dysfunction Dermatological Socioeconomic issues Cost (meds & monitoring) Discomfort Drug-Drug Effects Steroids Chemotherapy Anticoagulation Oral Contraceptives Anti-hypertensives Antibiotics

42.  Avoiding the Clots

43. DVT Prophylaxis after Stroke Prospective study, 1762 patients w/ stroke Randomized within 48 hours of stroke for 10 d Enoxaparin 40 mg SQ qd Unfractionated heparin 5000 units SQ q12h Similar symptomatic ICH (1%) Results Increase in major extracranial bleeding Enoxaparin reduced risk of VTE by 43%

44. DVT Prophylaxis after ICH No randomized trials of prophylactic anticoagulants Intermittent pneumatic compression devices better than elastic stockings alone Lacut K et al. Neurology. 2005;65:865-9 Anticoagulation for DVT appears safe Kelly J et al. Stroke. 2003;34;2999-3005

45.  Wake up Swinging

46. ICU Agitation Subtype of delirium Characterized by excessive behaviors Aggression Disinhibition Emotional lability Motor disturbances

47. Etiology Medical factors Infection, metabolic, pain Neurological factors Intracranial pressure, hydrocephalus Injury to fronto-temporal pathways Altered reactive response to stimuli Multiple cortical, subcortical & brainstem systems Alterations in neurotransmitters Catecholamines, serotonin, acetylcholine Alterations in sleep-wake cycles

48. Pharmacological Management Acute safety issues Long-term management Symptom guided treatment Aggression -- serotonin Memory -- acetylcholine Arousal / Attention -- catecholamines Motor disturbances -- dopamine Disinhibition/Lability -- combined

49. Potentially Harmful Agents Benzodiazepines Dopamine antagonists Neuromuscular blockade Anticholinergics H2 receptor antagonists: ranitidine, etc. Antihypertensives: clonidine, prazosin Anticonvulsants: phenytoin, phenobarbital

50. Pharmacological Management Antipsychotics Dopamine antagonists Treat aggression by causing sedation Good immediate intervention for safety issues May lower seizure threshold Paradoxical agitation Long term use can impair motor recovery Anxiolytics: Benzodiazepines GABA pathways Utility: rapid resolution of violent agitation May prolong coma; impair learning & memory Work synergistically with antipsychotics

51. Pharmacological Management Anticonvulsants: GABA & ?2-adrenergic pathways Treat impulse-control disorders, anxiety May slow reaction time & visuomotor speed Adjust dose by clinical response, not drug concentrations Stimulants: Dopamine agonists Treats agitation; improves motivation Agents: amantadine, bromocriptine, Sinemet �Works or doesn�t� -- effects noted within days Stimulants: Sympathomimetics (Catecholamine?) Treats attention / arousal problems, depression Agents: methylphenidate, d-amphetamine

52.  Nihilism or Hopefulness

53. Prognosis Predictive algorithms Clinical exam Electrophysiological studies Neuroimaging Family education

54. Prognosis Predictive algorithms Clinical exam Electrophysiological studies Neuroimaging Family education

55. Transition to Rehabilitation Early consultation with rehabilitation specialties PM&R involvement shortly after admission Multidisciplinary rounds PT, OT, Speech Mobilize patient Surgical interventions Tracheostomy, PEG tube, IVC filter Facilitation of transfer to rehabilitation setting Role of Care Management specialists

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