Intracerebral hemorrhage hypertensive

overview of management hypertensive intracerebral bleed

1. HYPERTENSIVE INTRACEREBRAL BLEED OVERVIEW OF MANAGEMENT Dr Swapnil Samadhiya SR DM Neurology GMC KOTA

2. More than 1 million annually worldwide , deadliest & most disabling ( Qureshi AI et al, N Engl J Med2001;344:1450–60 ) ∼10–15% of all stroke ( Mozaffarian D et al, Circulation2015;131:e29–322) m/c risk factor -Uncontrolled hypertension (HTN) Ariesen MJ et al, Stroke 2003;34:2060–5 ∼70–80% cases,spontaneous rupture of small vessels by HTN. Martini SR et al, Neurology2012;79:2275–82 Incidence higher Asians (limited primary care for HTN,non -compliance) van Asch CJ et al, Lancet Neurol2010;9:167–76

3. Intracerebral hemorrhage Small ICH Readily survivable with good medical care. Zahuranec DB et al, J Neurol Neurosurg Psychiatr2006;77:340–4 Large ICH Multidisciplinary care essential Specialised neurocritical care team Hospital stay duration and mortality reduction Suarez JI et al Crit CareMed2004;32:2311–7

4. Hypertension- non lobar ICH more common than lobar ICH Most common locations of hypertensive ICH are the putamen , thalamus, subcortical white matter, pons and cerebellum Martini SR, Flaherty ML, Brown WM,et al. Risk factors for intracerebral hemorrhage differ according to hemorrhage location. Neurology2012;79:2275–82

5. ED algorithm for early diagnosis and emergent intervention

6. EARLY DIAGNOSIS Rapid diagnosis,crucial for appropriate care and better functional outcomes. Suspect –Sudden onset, severe headache, vomiting, elevated systolic blood pressures or decreased level of consciousness. Smith EE et al, Neuroimaging Clin N Am2005;15:259–72, ix Non-contrast head CT is highly sensitive and specific for ICH and is the key to early diagnosis . Orito k,et alStroke2016;47:958–63

7. Acute Management of ICH Predicting hematoma expansion Preventing hematoma expansion Blood pressure control Reversing INR Platelet transfusion Metabolic Monitoring for complications of ICH Seizures Hydrocephalus

8. 24-48 12-24 0-3 6-12 3-6 hours from onset Stroke 1996;27:1783-87 Is it expanding?

9. Spot sign Wada et al., 2007

10. Select CT slice with largest ICH A = longest axis (cm) B = longest axis perpendicular to A (cm) C = number of slices x slice thickness (cm) A x B x C Calculating ICH volume 2

11. ICH volume > 30cc 1 < 30cc Intraventricular extension Yes 1 No Infratentorial location Yes 1 No Age > 80 1 < 80 Glasgow coma scale 3-4 5-12 13-15 2 1 Total score 0-6 Godoy, D. A. et al. Stroke 2006 Score 30-day mortality 0 0% 1 13 2 26 3 72 4 97 5, 6 100 ICH score

12. Impact of intraventricular blood _____ ICH =80 cc, GCS  8 …….. ICH =80 cc, GCS >8 __ __ ICH =20 cc, GCS  8 ----- ICH =20 cc, GCS >8 Tuhrim et al. Crit Care Med 1999;27:617-21

13. Preventing hematoma expansion Blood pressure control Reversing INR Platelet transfusion Metabolic

14. INTERACT 2 trial 2839 Patients within 6 hours of onset of ICH Treatment arm: SBP <140 Control arm: SBP <180 Intensive blood pressure lowering –better functional outcome at 90 days (MRS) Death and severe disability similar

15. Systolic BP time trends 1 hour - Δ14 mmHg (P<0.0001) 6 hour - Δ 14 mmHg (P<0.0001) Intensive group to target (<140mmHg) 462 (33%) at 1 hour 731 (53%) at 6 hours Mean Systolic Blood Pressure (mm Hg) 110 120 130 140 150 160 170 180 190 200 R 15 30 45 60 6 12 18 24 2 3 4 5 6 7 Standard Intensive // // Minutes Hours Days / Time 164 153 150 139 am pm am pm am pm am pm am pm am pm P<0.0001 beyond 15mins Target level INTERACT 2: results

16. ATACH-2 trial 1000 patients with acute ICH randomly assigned (within 4.5 hours) to a target SBP of 110 to 139 mmHg or a target SBP of 140 to 179 mmHg No differences in death or disability rates Rates of renal adverse events were higher in the intensive treatment group (9 versus 4 percent).

17. Meta-analysis with individual patient data of INTERACT2 and ATACH-2 trials Patients who achieved early, stable systolic blood pressure reduction in the first 24 hours to levels as low as 120 to 130 mmhg had more favorable outcomes Moullaali TJ, Wang X, Martin RH, et al. Blood pressure control and clinical outcomes in acute intracerebral haemorrhage : a preplanned pooled analysis of individual participant data. Lancet Neurol 2019; 18:857.

18. BP Control(AHA Statement) SBP between 150-220 mm Hg Without contraindication to acute BP treatment Lowering of SBP to 140 mm Hg is safe ( class1; Level of Evidence A ) Improving functional outcome ( class 2a; Level of Evidence B ) SBP>220 mm Hg Consider aggressive reduction of BP SBP of 140 to 160 mmHg is a reasonable target Continuous intravenous infusion and frequent BP monitoring ( class 2a; level of evidence C )

19. Useful intravenous agents for controlling blood pressure

20. Intracranial pressure management Increased intracranial pressure result from- Hematoma Mass effect(surrounding edema/hydrocephalus) Basic measures Head Elevation 30 degrees Mild sedation(as needed for comfort) Avoidance( endotracheal tube holder), securement device ties, constrictive central line dressings, twisting of the head might constrict cervical veins Normal saline(maintenance and replacement fluids)hypotonic fluids contraindicated Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032

21. Steroids for ICH: NO!!! Single-center, double-blind randomized trial Dexamethasone versus placebo within 48 hours of onset for 9 days total Trial halted after enrollment of 93 patients due to high rate of complications and no clinical benefit NEJM 1987;316:1229-1233

22. Invasive ICP Monitoring Glasgow coma scale (GCS) score <8 Clinical evidence of transtentorial herniation Significant intraventricular hemorrhage Hydrocephalus Goal -cerebral perfusion pressure (CPP) of 50 to 70 mmHg High quality data lacking

23. Rapid, noninvasive test Measuring optic nerve sheath diameter using ocular ultrasound is an accurate method for detecting elevated ICP Dilated op Optic nerve sheath measuring 5.3 mm in a patient Increased intracranial pressure Patterson DF , Ho ML, Leavitt JA, et al. Comparison of Ocular Ultrasonography and Magnetic Resonance Imaging for Detection of Increased Intracranial Pressure. Front Neurol 2018; 9:278.

24. Cerebrospinal fluid drainage Reduce elevated ICP,reasonable for patients Hydrocephalus Trapped ventricle Poor GCS patients Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032

25. Osmotic therapy Hypertonic saline or mannitol No compelling evidence to support the superiority of either agent Some studies suggest that hypertonic saline is more effective Kamel H, Navi BB, Nakagawa K, et al. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med 2011; 39:554

26. Mannitol Hypertonic saline Quick and effective Initial bolus of 0.5 to 1 g/kg, f/b repeated infusions of 0.25 to 0.5 g/kg every 4 to 12 hours,monitor serum osmolality Goal-plasma hyperosmolality (300 to 310 mosmol /kg) Avoid Plasma osmolal gap > 55 mosmol /kg &dose > 250 mg/kg every four hours Reversible acute renal failure Ropper AH. Management of raised intracranial pressure and hyperosmolar therapy . Pract Neurol 2014; 14:152 3 %, m/ c,continuous infusion ( can given intermittent bolus), 23.4 %(intermittent bolus) Sodium goal - 145 to 155 meq /L Circulatory overload,pulmonary edema,non -anion gap metabolic acidosis(chloride)

27. Salvage therapies Reduce ICP if cerebrospinal fluid drainage or osmotic therapy fail to lower ICP Pharmacologic coma Hyperventilation Neuromuscular blockade

28. Pharmacologic coma Reduce cerebral metabolism Pentobarbital Severe side effects(arterial hypotension),variable benefit,avoid Continuous monitoring with electroencephalography during treatment, dose titrated to a burst-suppression pattern Propofol - Loading dose of 1 to 3 mg/kg, infusion5 to 50 mcg/kg per minute, with a maximum dose of 200 µg/kg per minute Hypotension,acute refractory bradycardia , metabolic acidosis, cardiovascular collapse, rhabdomyolysis , hyperlipidemia , renal failure,hepatomegaly Schwab S, Spranger M, Schwarz S, Hacke W. Barbiturate coma in severe hemispheric stroke: useful or obsolete? Neurology 1997; 48:1608

29. Hyperventilation Rapid lowering induce cerebral vasoconstriction Effect lasts few hours (Paco 2 ) goal 30 to 35 mmhg . More aggressive hyperventilation (paco 2 of 26 to 30 mmhg )brain ischemia and worse outcomes Reserve for refractory Acute brain herniation until more definitive therapies can be implemented Freeman WD. Management of Intracranial Pressure. Continuum ( Minneap Minn ) 2015; 21:1299

30. Neuromuscular blockade Not responsive to analgesia and sedation. Muscle activity increase ICP,raising intrathoracic pressure,reducing cerebral venous outflow Increased risk of pneumonia and sepsis Ability to evaluate the neurologic status is lost once the patient is paralyzed

31. 282 ICH cases imaged at onset and at 72 hours, including 70 (25%) taking antiplatelet medication No difference in baseline hematoma volume No difference in hematoma growth at 72 hours No difference in need for surgical evacuation No difference in Rankin score at 90 days No difference in mortality Platelet transfusion for ASA use?

32. Platelet Transfusion AHA Statement The usefulness of platelet transfusions in ICH patients with a history of antiplatelet use is uncertain ( class 2b: Level of Evidence C ) Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate factor replacement therapy or platelets, respectively ( class 1; Level of Evidence C )

33. 2300 subjects, within eight hours of symptom onset At 90 days, no difference in functional status or mortality between the two treatment groups, despite early reductions in hematoma growth (at day 2) and death (at day 7) for the tranexamic acid group.

34. Used for hemophiliacs with Factor VIII antibodies FAST Trial Phase 3 trial of Factor VII for acute ICH (not on warfarin ) Primary outcome: severe disability or death at 90 days 821 patients randomized to placebo, 20, or 80 mcg/kg Treatment started within 4 hours of onset Reduced ICH growth with 80 mcg/kg vs placebo Time mattered: earlier treatment => less growth NEJM 2008;358:2127-2137 Factor VII for acute ICH

35. 90 day death/severe disability No clinical benefit MI and ischemic stroke absolute risk increased 5% AHA Statement Increase thromboembolic risk Not recommended ( class 3; Level of Evidence A )

36. Metabolic Hyperglycemia and hypoglycemia should be avoided( 140 to 180 mg/ dL ) ( class 1; Level C ) Fever after ICH may be reasonable ( class 2b; Level C ) Systemic screening for MI with ECG and cardiac enzyme testing after ICH is reasonable ( class 2a; Level C ) Dysphagia screen all patients before initiating oral intake to reduce pneumonia risk ( class 1; Level B ) ,GCS <8 be intubated to decrease the risk of aspiration Proton pump inhibitors, histamine-2 receptor antagonists ass/w increased risk hospitalacquired pneumonia, Clostridioides difficile infection, other enteric infections; routine use should be avoided

37. Pathogenesis of secondary brain insult of hypertensive intracerebral hemorrhage

38. Complications of ICH Seizures Hydrocephalus DVT/PE

39. Seizures Approx.15 percent Lobar >Deep hemorrhage Prophylactic antiseizure medication is not recommended ( class 3; Level B ) Clinical Seizures should be treated with antiseizure medication (Class 1;Level A) Continuous EEG monitoring , depressed mental status that’s out of proportion to degree of brain injury ( Class 2a; Level C ) and should be treated with antiseizure medication if found to have electrographic seizures on EEG ( class 1; Level C )

40. Hydrocephalus Headache Vomiting Drowsiness → Coma EVD- decreased level of consciousness ( class 2a; Level B)

41. DVT Risk of DVT in hemiplegic patients is 10-50% during acute hospitalization AHA STATEMENT Intermittent pneumatic compression must be used immediately ( class 1; Level A ) Graduated compression stockings are not beneficial to reduce DVT or improve out comes ( class 3; Level A ) After 1-4 days from onset LMW heparin or unfractionated heparin.

42. Intraventricular Hemorrhage Intraventricular administration of rtPA ,fairly low complication rate, efficacy and safety uncertain ( class 2b; Level B ) Efficacy of endoscopic treatment of IVH is uncertain ( class 2b; Level B )

43. 1033 patients randomized Multicenter international randomized trial of early surgery versus medical management for ICH Crossover to surgery possible, so NOT strictly a trial of surgery versus medicine Surgeon uncertain about benefit of surgery Randomization within 72 hours of ICH; surgery within 24 hours of randomization Supratentorial ICH only STICH Trial Mendelow et al. Lancet 2005

44. STICH Results

45. STITCH II trial

46. Surgery Cerebellar hemorrhage , deteriorating neurologically , brain stem compression,hydrocephalus surgical removal as soon as possible ( class 1; Level C ) Initial treatment with ventricular drainage rather than surgical evacuation is not recommended ( class 3; Level C ) Supratentorial ICH , usefulness of surgery not well established ( class2b; Level A ) Policy of early hematoma evacuation not clearly beneficial compared to hematoma evacuation when patient deteriorates ( Class 2b; Level A )

47. Surgery Indication vary with the site of the bleed Cerebellar hemorrhage >3 cm diameter, volume >14 cm3 , deteriorating neurologically ,brainstem compression,hydrocephalus 2019 meta-analysis matched 152 patients who had surgical hematoma evacuation with 152 patients who had conservative treatment Surgical hematoma evacuation increased probability of survival at three months(78 % vs 61%) Overall likelihood of a favorable functional outcome similar Kuramatsu JB, Biffi A, Gerner ST , et al. Association of Surgical Hematoma Evacuation vs Conservative T reatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage. JAMA 2019; 322:1392

48. Supratentorial hemorrhage Controversial Indications not been conclusively defined Reserve surgical therapy for patients with life-threatening mass effect from supratentorial ICH Limited data -reduce mortality( comatose,large hematoma with significant midline shift, elevated intracranial pressure (ICP) refractory to medical management) Routine evacuation of supratentorial ICH in the first 96 hours is not recommended Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032

49. Open craniotomy 2008 meta-analysis reviewed 10 randomized trials including 2059 patients Associated with a reduced risk of death and dependency (odds ratio 0.71; 95% ci 0.61 to 0.91) Benefit was not robust, and there was significant heterogeneity for death as an outcome STICH trial , largest, 503 patients, median time to surgery was 30 hours after hemorrhage onset, favorable outcome at six months

50. Minimally invasive techniques MISTIE III no clear benefit 516 patients with spontaneous, supratentorial ICH of ≥30 mL At one year , the number of patients who achieved a good functional outcome similar for the minimally invasive surgery group compared with the standard care group (45 versus 41 percent) Mortality was lower in the minimally invasive surgery (19 versus 26 percent)

51. SECONDARY TREATMENT ISSUES Resumption benefit of aspirin (non-lobar ICH> lobar ICH) At 10 days, rebleeding unlikely typically should be not be restarted until at least one to two weeks after ICH. As soon as 48 hours, after ICH in stable patients who require it. Hemphill JC 3 rd et al, Stroke 2015; 46:2032 Lower dose (30 to 160 mg daily) effective and safer

52. Resumption of anticoagulation Avoidance of long term AC for nonvalvular AF is probably recommended after AC associated spontaneous lobar ICH due to relatively high risk of recurrence ( class 2a; Level B ) AC after nonlobar ICH and antiplatelet therapy after an ICH might be considered, particularly when there is strong indication ( class 2b; Level B ) Optimal timing to resume AC after ICH is uncertain. Avoidance of AC for at least 4 weeks in patients without mechanical valves, might decrease ICH recurrence ( class 2b; Level B ) Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032

53. Secondary prevention PROGRESS trial 6000 patients with prior cerebrovascular events Mean baseline blood pressure of 147/86,a modest reduction in blood pressure of 9/4 mmhg decreased the rate of ICH by 50%(95% CI 26-67)

54. SPARCL trial statins might increase the risk of ICH in patients with a previous ischemic stroke or ICH Conflicting data, it seems to be reasonable to weigh the benefits and possible risks of statin therapy in individual patients

55. PROGNOSIS Risk factors for poor outcomes Increasing age Decreasing Glasgow Coma Scale (GCS) score(eight or less),Early neurologic deterioration within 48 hours after ICH onset Increasing ICH volume(>60 cm 3 on initial CT) ,Hematoma growth(first 24 hours)10 % increase,5 % more likely to die Intraventricular hemorrhage Deep or infratentorial ICH location Preceding oral anticoagulation therapy, and possibly antiplatelet therapy

56. PROGNOSIS Risk factors for poor outcomes Early withdrawal of support Elevated admission blood glucose Lower serum levels of low density lipoprotein cholesterol (LDL-C) Elevated C-reactive protein levels Extensive white matter lesions on CT or magnetic resonance imaging (MRI)

57. GCS score-Useful predictor of 30-day mortality GCS scores 3 to 4 7 to 10 11 to 12 13 to 14 15 Predicted 30-day survival rates 5% 35 % 55 % 70% 90%

58. The FUNC score. Stroke 2008; 39:2304. DOI: 10.1161/STROKEAHA.107.512202 No patient assigned a FUNC score ≤4 achieved functional independence, whereas >80 percent with a score of 11 died

59. ICH Recurrence Risk factors for recurrent ICH Uncontrolled hypertension Lobar location of initial ICH Older age Male gender Ongoing anticoagulation Apolipoprotein E epsilon 2 or epsilon 4 alleles Greater number of microbleeds on MRI Ischemic stroke history Black race Hispanic ethnicity Poon MT , Fonville AF , Al- Shahi Salman R. Long-term prognosis after intracerebral haemorrhage : systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2014; 85:660

60. REFERENCES AHA/ASA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032 Kuramatsu JB, Biffi A, Gerner ST , et al. Association of Surgical Hematoma Evacuation vs Conservative T reatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage. JAMA 2019; 322:1392 Poon MT , Fonville AF , Al- Shahi Salman R. Long-term prognosis after intracerebral haemorrhage : systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2014; 85:660 Martini SR, Flaherty ML, Brown WM,et al. Risk factors for intracerebral hemorrhage differ according to hemorrhage location. Neurology2012;79:2275–82 Freeman WD. Management of Intracranial Pressure. Continuum ( Minneap Minn ) 2015; 21:1299 Ropper AH. Management of raised intracranial pressure and hyperosmolar therapy. Pract Neurol 2014; 14:152

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