Transcript
Page 1: Spontaneous intracerebral hemorrhage

Pratap Sagar Tiwari

, Internal Medicine, NGMC, Nepal

SPONTANEOUS INTRACEREBRAL HEMORRHAGE: PROGNOSIS AND TREATMENT

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MORTALITY AND FUNCTIONAL OUTCOME

• The 30-day mortality from ICH ranges from 35 to 52 percent [1-8], one-half of these deaths occur within the first two days [3,7,9]

1. Anderson CS, Chakera TM, Stewart-Wynne EG, Jamrozik KD. Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome. J Neurol Neurosurg Psychiatry 1994; 57:936.

2. Counsell C, Boonyakarnukul S, Dennis M, et al. Primary intracerebral hemorrhage in the Oxford-shire community Stroke Project. Cerebrovasc Dis 1995; 5:26.

3. Broderick JP, Brott TG, Duldner JE, et al. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. stroke 1993; 24:987.

4. Fogelholm R, Murros K, Rissanen A, Avikainen S. Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry 2005; 76:1534.

5. Flaherty ML, Haverbusch M, Sekar P, et al. Long-term mortality after intracerebral hemorrhage. Neurology 2006; 66:1182.

6. Sacco S, Marini C, Toni D, et al. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke 2009; 40:394.

7. Zia E, Engström G, Svensson PJ, et al. Three-year survival and stroke recurrence rates in patients with primary intracerebral hemorrhage. Stroke 2009; 40:3567.

8. van Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9:167.

9. Franke CL, van Swieten JC, Algra A, van Gijn J. Prognostic factors in patients with intracerebral haematoma. J Neurol Neurosurg Psychiatry 1992; 55:653.

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MORTALITY AND FUNCTIONAL OUTCOME

• Furthermore, only a small number of patients function independently after the event.

• In a prospective study of 166 patients with spontaneous ICH from a large US metropolitan area, only 12 percent were normal or minimally handicapped at 30 days [1].

• A systematic review estimated that between 12 and 39 percent of patients achieve independent function [2].

1. Daverat P, Castel JP, Dartigues JF, Orgogozo JM. Death and functional outcome after spontaneous intracerebral hemorrhage. A prospective study of 166 cases using multivariate analysis. Stroke 1991; 22:1.

2. van Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9:167.

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MODIFIED RANKIN SCALEScore Description

0 No symptoms at all

1 No significant disability despite symptoms; able to carry out all usual duties and activities

2 Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance

3 Moderate disability; requiring some help, but able to walk without assistance

4 Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance

5 Severe disability; bedridden, incontinent and requiring constant nursing care and attention

6 Dead

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MORTALITY AND FUNCTIONAL OUTCOME

• A study (SIVMS:90 vs OXVASC:60 )found that hemorrhage from a cerebral arteriovenous malformation were associated with a lower case-fatality rate, despite a similar hemorrhage volume and a higher admission GCS compared with spontaneous ICH(12 VS 61 %) [1].

• Mortality was also reported to be low (1 of 22) in a cohort of children with ICH in whom vascular malformations was the identified etiology in 91 percent [2].

1. van Beijnum J, Lovelock CE, Cordonnier C, et al. Outcome after spontaneous and arteriovenous malformation-related intracerebral haemorrhage: population-based studies. Brain 2009; 132:537.

2. Beslow LA, Licht DJ, Smith SE, et al. Predictors of outcome in childhood intracerebral hemorrhage: a prospective consecutive cohort study. Stroke 2010; 41:313.

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LONG TERM MORTALITY AND FUNCTIONAL OUTCOME

• A retrospective cohort study identified 411 patients with 1st ever ICH and found that the annual risk of dying compared with controls was increased 4.5-fold during the 1st yr after ICH and 2.2-fold during years 2-6 [1].

• A subsequent longitudinal prospective cohort study evaluated patients(n:140) who had survived the first 3 mnths after ICH and observed that mortality at 7yrs was significantly higher than controls(n:260) (32.9 vs 19.4 %) [2].

• In a population-based cohort of patients(n:1224) hospitalized after ICH in the Greater Cincinnati/Northern Kentucky area, the 10yr survival was 18% [3]

1. Fogelholm R, Murros K, Rissanen A, Avikainen S. Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry 2005; 76:1534.

2. Saloheimo P, Lapp TM, Juvela S, Hillbom M. The impact of functional status at three months on long-term survival after spontaneous intracerebral hemorrhage. Stroke 2006; 37:487.

3. Flaherty ML, Haverbusch M, Sekar P, et al. Long-term mortality after intracerebral hemorrhage. Neurology 2006; 66:1182.

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What are the important prognostic factors ???

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PROGNOSTIC FACTORS

• Initial ICH volume and level of consciousness

• Hematoma growth

• Intraventricular extension

• Early neurologic deterioration

• Preceding antithrombotic use

1. Oral anticoagulants

2. Antiplatelets

• Limiting care and other factors

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INITIAL ICH VOLUME AND LEVEL OF CONSCIOUSNESS

In a study of 188 patients with ICH that analyzed predictors of 30-day mortality [1]; the following observations were made:

• An ICH vol of ≥60 cm3 on initial CT and a GCS score of ≤8 predicted a 30-day mortality of 91 %.

• An ICH vol <30 cm3 and a GCS score of ≥9 predicted a 30-day mortality of 19 %..

1. Fogelholm R, Murros K, Rissanen A, Avikainen S. Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry 2005; 76:1534 .

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HEMATOMA GROWTH

• In a meta-analysis of 218 patients with spontaneous ICH who had a head CT scan within three hours of onset and follow-up head CT within 24 hours, each 10 % increase in ICH growth was associated with increased mortality (hazard ratio 1.05, 95% CI 1.03-1.08) and worse outcome as measured by the modified Rankin scale (odds ratio 0.84, 95% CI 0.75-0.92) [1].

• That is, for each 10 % increase in hematoma volume, patients were 5 percent more likely to die and 16 % more likely to increase one point on the modified Rankin scale..

1. Davis SM, Broderick J, Hennerici M, et al. Hematoma growth is a determinant of mortality and poor outcome after

intracerebral hemorrhage. Neurology 2006; 66:1175 .

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INTRAVENTRICULAR EXTENSION

• One of the largest of these reports evaluated 406 patients with ICH, 45 % of whom had intraventricular extension of hemorrhage. [1].

• After controlling for age and ICH volume, a poor outcome at discharge (defined as a modified Rankin scale score of 4 to 6) was significantly more likely in patients with intraventricular hemorrhage than in those without intraventricular hemorrhage (odds ratio 2.25, 95% CI 1.40-3.64)..

1. Hallevi H, Albright KC, Aronowski J, et al. Intraventricular hemorrhage: Anatomic relationships and clinical implications. Neurology 2008; 70:848.

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EARLY NEUROLOGIC DETERIORATION

• In a prospective study of 266 patients with ICH admitted within 12 hrs of stroke onset, early neurologic deterioration occurred in 61 (23%) and was associated with an 8-fold ↑ in the probability of a poor outcome (95% CI 2.7-25.5) [1].

• Independent predictors of early neurologic deterioration on admission included elevations in body temperature, neutrophil count, and serum fibrinogen level (odds ratios 24.5, 2.1, and 5.6, respectively), all of which could be interpreted as markers of an inflammatory response.

• Factors measured at 48 hours that were associated with early neurologic deterioration included ICH growth on repeat head CT, intra ventricular bleeding, and high systolic BP.

1. Leira R, Dávalos A, Silva Y, et al. Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology 2004; 63:461.

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PRECEDING ANTITHROMBOTIC USE

• Patients on oral anticoagulant therapy have a mortality rate of 52-73 % after ICH .(1,2,3)

1. Saloheimo P, Ahonen M, Juvela S, et al. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006; 37:129.

2. Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke 1995; 26:1471.

3. Rosand J, Eckman MH, Knudsen KA, et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004; 164:880.

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ORAL ANTICOAGULANTS

• In a study that analyzed data from 303 patients in the placebo arm of a prospective trial of a putative neuroprotective drug for ICH, there were 21 patients receiving oral anticoagulants at the time of ICH onset [1].

• Patients with oral anticoagulant-related ICH had a significantly higher mortality rate at 90 days than those with spontaneous ICH (62 versus 17 %).

• In addition, the proportion of patients with hemorrhage expansion at 72 hours was significantly higher among those with anticoagulant-related ICH (56 versus 26 percent)..

1. Cucchiara B, Messe S, Sansing L, et al. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke 2008; 39:2993.

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ANTIPLATELETS

• A population-based study from Finland reported that regular aspirin use at the onset of ICH was a significant independent risk factor for death within three months of ICH (RR 2.5; 95% CI 1.3-4.6) [1].

• A systematic review of 25 cohort studies concluded that prior antiplatelet use was associated with increased mortality (OR = 1.3), but not poor functional outcome after ICH [2].

1. Saloheimo P, Ahonen M, Juvela S, et al. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006; 37:129.

2. Thompson BB, Béjot Y, Caso V, et al. Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review. Neurology 2010; 75:1333.

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REVERSAL OF ANTICOAGULATION RECOMMENDATION• For patients who develop an ICH, all anticoagulant and antiplatelet drugs should be

discontinued acutely for at least one to two weeks after the onset of hemorrhage, [1,2].

• Aggressive use of intravenous vitamin K and other factors may be necessary in patients who suffer an ICH while taking warfarin. (class I. Level of Evidence: B)

• There is a risk of creating a prothrombotic state when acutely reversing anticoagulation in a patient with atrial fibrillation; however, the risk of extending the hemorrhage outweighs this potential risk [3].

• Protamine sulfate is recommended for urgent treatment of patients with heparin-associated ICH [1,2]. (class I. Level of Evidence: B)

1. Broderick J, Connolly S, et al. Guidelines for the management of spontaneous intracerebral hemorrhage .A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2010

2. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke 2011; 42:227.

3. Genewein U, Haeberli A, Straub PW, Beer JH. Rebound after cessation of oral anticoagulant therapy: the biochemical evidence. Br J Haematol 1996; 92:479.

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REVERSING ANTICOAGULATION IN WARFARIN-ASSOCIATED INTRACEREBRAL HEMORRHAGE

* A total of 10 mg intravenously by slow infusion throughout 10 minutes.

Reproduced with permission from: Aguilar MI, Hart RG, Kase CS, et al. Treatment of warfarin-associated intercerebral hemorrhage: Literature review and expert opinion. Mayo Clin Proc 2007; 82:82. Copyright ©2007 Dowden Health Media.

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ADDITIONAL MANAGEMENT ISSUES

• Keeping the systolic blood pressure <180 mmHg during the acute phase is advisable.

• Given the high mortality accompanying AAICH, surgical evacuation of the hematoma after reversing anticoagulation can be considered in selected patients.

• For patients who will resume anticoagulation, Warfarin can be restarted at 7 to 10 days. (class IIb. Level of Evidence: B)

• Pneumatic compression stockings and early ambulation should be considered if leg paresis is present. (class I. Level of Evidence: B)

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PREDICTING MORTALITY AFTER ICH :ICH SCORE (1)Variables Score

GCS 3 TO 45 TO 1213 TO 15

210

ICH VOL ≥30 cm3 <30 cm3

10

IV extension Present Absent

10

Infratentorial origin YesNo

10

Age ≥80 <80

10

1. Hemphill JC 3rd, Bonovich DC, Besmertis L, et al. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001; 32:891.

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30-DAY MORTALITY RATES A/W ICH SCOREICH SCORE Mortality rate

1 13

2 26

3 72

4 97

5 100

The ICH score has been validated by retrospective [1] and prospective [2,3] analysis.

1. Cheung RT, Zou LY. Use of the original, modified, or new intracerebral hemorrhage score to predict mortality and morbidity after intracerebral hemorrhage. Stroke 2003; 34:1717.2. Godoy DA, Piñero G, Di Napoli M. Predicting mortality in spontaneous intracerebral hemorrhage: can modification to original score improve the prediction? Stroke 2006; 37:1038.3. Hemphill JC 3rd, Farrant M, Neill TA Jr. Prospective validation of the ICH Score for 12-month functional outcome. Neurology 2009; 73:1088 .

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LIMITING CARE & OTHER FACTORS

• Accumulating data suggest that the early use of DNR orders, along with decisions to limit aggressive treatments and/or withdraw medical care may negatively influence outcome in patients with ICH [1,2].

• Current guidelines suggest careful consideration of aggressive full care during the first 24 hours after ICH onset and postponement of new DNR orders during that time [3,4].

1. Zahuranec DB, Morgenstern LB, Sánchez BN, et al. Do-not-resuscitate orders and predictive models after intracerebral hemorrhage. Neurology 2010; 75:626.

2. Creutzfeldt CJ, Becker KJ, Weinstein JR, et al. Do-not-attempt-resuscitation orders and prognostic models for intraparenchymal hemorrhage. Crit Care Med 2011; 39:158.

3. Broderick J, Connolly S, et al. Guidelines for the management of spontaneous intracerebral hemorrhage .A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2010

4. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41:2108.

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OTHER FACTORS: HYPERGLYCEMIA

• A number of reports have noted that elevated admission blood glucose after ICH is a poor prognostic indicator [1,2,3,4,5].

1. Fogelholm R, Murros K, Rissanen A, Avikainen S. Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry 2005; 76:1534.

2. Franke CL, van Swieten JC, Algra A, van Gijn J. Prognostic factors in patients with intracerebral haematoma. J Neurol Neurosurg Psychiatry 1992; 55:653.

3. Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology 2003; 61:1351.

4. Fogelholm R, Murros K, Rissanen A, Avikainen S. Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study. J Neurol Neurosurg Psychiatry 2005; 76:349.

5. Appelboom G, Piazza MA, Hwang BY, et al. Severity of intraventricular extension correlates with level of admission glucose after intracerebral hemorrhage. Stroke 2011; 42:1883.

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HYPERGLYCEMIA: RECOMMENDATION

• The American Heart Association/American Stroke Association guidelines recommend treatment with insulin for patients who have serum glucose concentrations >140 (>7.8) [1,2].

• The European Stroke Initiative guidelines recommend treatment for glucose >180 mg/dL (>10 mmol/L) [3].

1. Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007; 38:1655.

2. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 2007; 38:2001.

3. European Stroke Initiative Executive Committee, EUSI Writing Committee, Olsen TS, et al. European Stroke Initiative Recommendations for Stroke Management-update 2003. Cerebrovasc Dis 2003; 16:311.

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OTHER FACTORS: CHOLESTEROL /STATIN

• A study had found that low LDL cholesterol levels on admission were associated with increased mortality(n:88) [1].

• Low total and LDL cholesterol have been linked to a risk of death in ICH. In one study of 108 patients with ICH, lower serum LDL-cholesterol predicted early hematoma growth, neurologic deterioration, and three-month mortality [2].

1. Ramírez-Moreno JM, Casado-Naranjo I, Portilla JC, et al. Serum cholesterol LDL and 90-day mortality in patients with intracerebral hemorrhage. Stroke 2009; 40:1917.

2. Rodriguez-Luna D, Rubiera M, Ribo M, et al. Serum low-density lipoprotein cholesterol level predicts hematoma growth and clinical outcome after acute intracerebral hemorrhage. Stroke 2011; 42:2447.

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OTHER FACTORS: CHOLESTEROL /STATIN

• One case-control study found that statin use prior to ICH was associated with reduced mortality (OR 0.47) and increased probability of a favorable outcome (OR = 2.08) with similar results found in a meta-analysis of published studies of ICH and statin use (n:936 vs 2284) [1].

1. Biffi A, Devan WJ, Anderson CD, et al. Statin use and outcome after intracerebral hemorrhage: case-control study and meta-analysis. Neurology 2011; 76:1581.

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RECOMMENDATION: CHOLESTEROL /STATIN

• Given the conflicting data, it seems to be reasonable to weigh the benefits and possible risks of statin therapy in individual patients who are at risk for ICH recurrence.(1,2,3)

1. Westover MB, Bianchi MT, Eckman MH, Greenberg SM. Statin use following intracerebral hemorrhage: a decision analysis. Arch Neurol 2011; 68:573.

2. Goldstein LB. Statins after intracerebral hemorrhage: to treat or not to treat. Arch Neurol 2011; 68:565.

3. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 2009; 8:453.

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OTHER FACTORS: FEVER

• A meta-analysis analyzed fever and outcome in patients with neurologic injury, including hemorrhagic and/or ischemic stroke [1].

• Fever was significantly associated with increased mortality rates, greater disability, more dependence, worse functional outcome, greater severity, and longer intensive care unit and hospital stays.

1. Greer DM, Funk SE, Reaven NL, et al. Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis. Stroke 2008; 39:3029.

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FEVER• The PAIS trial evaluated 1400 adults no later than 12 hours after symptom onset of acute

ischemic stroke and intracerebral hemorrhage [1]. Included patients had a body temperature of 36ºC to 39ºC. Compared with placebo, paracetamol (acetaminophen) 1 g six times daily for three days did not improve outcome [1].

• In a systematic review and meta-analysis of five small randomized controlled trials with a total of 293 patients, there was no benefit for pharmacologic temperature reduction for acute stroke [2]. All the trials enrolled patients within 24 hours of stroke onset, and the duration of treatment ranged from 24 hours to five days. With addition of results from the PAIS trial, the updated meta-analysis found no difference between active treatment and control for a favorable outcome (odds ratio 1.1, 95% CI 0.9-1.3) [1].

1. den Hertog HM, van der Worp HB, van Gemert HM, et al. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial. Lancet Neurol 2009; 8:434.

2. Den Hertog HM, van der Worp HB, Tseng MC, Dippel DW. Cooling therapy for acute stroke. Cochrane Database Syst Rev

2009; :CD001247.

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RECOMMENDATION ON FEVER

• The source of fever should be investigated and treated, and antipyretics should be used to lower temperature in febrile patients with acute stroke [1,2].

• It is suggested maintain normothermia for at least the first several days after an acute stroke [3].

• Induced hypothermia is not currently recommended for patients with ischemic stroke [1], outside of clinical trials.

1. Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007; 38:1655.

2. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 2007; 38:2001.

3. Ginsberg MD, Busto R. Combating hyperthermia in acute stroke: a significant clinical concern. Stroke 1998; 29:529.

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RECURRENCE

• Recurrent hypertensive ICH occurs in as many as 5 percent of patients [1,2,3,4].

• Recurrence is most common within two years of the first hemorrhage [3], with the most important risk factor being uncontrolled hypertension [2].

1. Zia E, Engström G, Svensson PJ, et al. Three-year survival and stroke recurrence rates in patients with primary intracerebral hemorrhage. Stroke 2009; 40:3567.

2. Chen ST, Chiang CY, Hsu CY, et al. Recurrent hypertensive intracerebral hemorrhage. Acta Neurol Scand 1995; 91:128.

3. Bae H, Jeong D, Doh J, et al. Recurrence of bleeding in patients with hypertensive intracerebral hemorrhage. Cerebrovasc Dis 1999; 9:102.

4. Hanger HC, Wilkinson TJ, Fayez-Iskander N, Sainsbury R. The risk of recurrent stroke after intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 2007; 78:836.

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RISK FACTORS FOR RECURRENT ICH

Risk factors for recurrent ICH include [1]:

• Uncontrolled hypertension

• Lobar location of initial ICH

• Older age

• Ongoing anticoagulation

• Greater number of microbleeds on MRI1. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral

hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41:2108.

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INTRACRANIAL PRESSURE CONTROL

• Elevate the head of the bed to 30 degrees, once hypovolemia is excluded.

• Analgesia and sedation, particularly in unstable, intubated patients

• Suggested intravenous agents for sedation are propofol, or midazolam.

• Suggested agents for analgesia and antitussive effect are morphine or alfentanil.

• Glucocorticoids should not generally be used to lower the ICP in patients with ICH. A randomized trial found that dexamethasone did not improve outcome but did increase complication rates, primarily infection [1].

1. Poungvarin N, Bhoopat W, Viriyavejakul A, et al. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage. N Engl J Med 1987; 316:1229.

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MANAGING ICP

• Monitoring and treatment of ICP should be considered for patients with GCS <8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus [1].

1. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41:2108.

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LOWERING ICP• Intravenous mannitol is the treatment of choice to lower increased intracranial

pressure, effectively lowering ICP and benefiting brain metabolism [1].

• It is administered as an initial bolus of 1 g/kg, followed by infusions of 0.25 to 0.5 g/kg every six hours.

• The goal of therapy is to achieve plasma hyperosmolality (300 to 310 mosmol/kg) while maintaining an adequate plasma volume; major side effects include hypovolemia and a hyperosmotic state [2].

• Normal saline initially should be used for maintenance and replacement fluids; hypotonic fluids are contraindicated.

• Dextrose-containing fluids should be avoided unless hypoglycemia is present or strongly suspected because

excessive glucose may be injurious to stroke patients. [2]. 1. Helbok R, Kurtz P, Schmidt JM, et al. Effect of mannitol on brain metabolism and tissue oxygenation in severe haemorrhagic stroke. J Neurol Neurosurg

Psychiatry 2011; 82:378.

2. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 2007; 38:2001.

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BLOOD PRESSURE CONTROL

• Severe elevations in blood pressure may worsen ICH by representing a continued force for bleeding [1].

• However, an increased MAP may be necessary to maintain cerebral perfusion in some patients, and lowering the arterial pressure (eg, to a systolic blood pressure [SBP] below 130 mmHg) may cause ischemia and worsen neurologic injury.)

• Note: MAP- ICP= CPP1. Ohwaki K, Yano E, Nagashima H, et al. Blood pressure management in acute intracerebral hemorrhage:

relationship between elevated blood pressure and hematoma enlargement. Stroke 2004; 35:1364.

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BLOOD PRESSURE CONTROL• In a RCT (INTERACT) of 404 patients with acute spontaneous ICH, intensive bp lowering

treatment (target SBP 140 mmHg) compared with traditional management (target SBP 180 mmHg) was a/w a reduction in hematoma growth at 24 hours (14 versus 26 percent) [1,2].

• A larger trial (INTERACT2) is in progress.

• Smaller, nonrandomized studies(including ATACH) have also found that more aggressive blood pressure lowering is associated with strong trends toward reduced hematoma enlargement [2,3,4,5]. In some studies, there were also trends toward reduced perilesional edema and better clinical outcomes.

1. Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol 2008; 7:391.

2. Anderson CS, Huang Y, Arima H, et al. Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT). Stroke 2010; 41:307.

3. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 2007; 38:2001.

4. Qureshi AI, Mohammad YM, Yahia AM, et al. A prospective multicenter study to evaluate the feasibility and safety of aggressive antihypertensive treatment in patients with acute intracerebral hemorrhage. J Intensive Care Med 2005; 20:34.

5. Qureshi AI, Palesch YY, Martin R, et al. Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. Arch Neurol 2010; 67:570.

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GUIDELINES (CLASS IIB; LOE-C) 1• For patients with SBP >200 mmHg or MAP >150 mmHg: consider aggressive reduction

of BP with continuous intravenous infusion of medication accompanied by frequent (every 5 min) BP monitoring

• For patients with SBP >180 mmHg or MAP >130 mmHg and evidence or suspicion of elevated ICP : consider monitoring ICP and reducing blood pressure using intermittent or continuous intravenous medication to keep cerebral perfusion pressure in the range of 61 to 80 mmHg

• For patients with SBP >180 mmHg or MAP >130 mmHg and no evidence or suspicion of elevated ICP: consider a modest reduction of blood pressure (eg, target MAP of 110 mmHg or target blood pressure of 160/90 mmHg) using intermittent or continuous intravenous medication, and clinically reexamine the patient every 15 minutes

1. Broderick J, Connolly S, et al. Guidelines for the management of spontaneous intracerebral hemorrhage .A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2010

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RECOMMENDED AGENTS

Labetalol,nicardipine, esmolol, enalapril, hydralazine, nitroprusside, and nitroglycerin are useful intravenous agents for controlling blood pressure [1].

1. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 2007; 38:2001.

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SEIZURE PROPHYLAXIS AND TREATMENT• The risk of seizures in patients with acute spontaneous ICH ranges from 4.2 to 29 percent [1].

Seizures are more common in lobar as compared to deep hemorrhage [3].

• If a seizure occurs, appropriate iv AED treatment should be administered to prevent recurrent seizures [2].

• The choice of the initial antiepileptic agent depends upon individual circumstances and contraindications.

• Current guidelines suggest the use of intravenous fosphenytoin or phenytoin in this setting [1].

• While some experts suggest a brief period of AED prophylaxis soon after ICH onset as a potential means of reducing the risk for early seizures in patients with lobar hemorrhages [1], 2010 guidelines recommend against prophylactic use of AEDs [2]

1. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 2007; 38:2001.

2. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41:2108.

3. Kuramatsu JB, Sauer R, Mauer C, et al. Correlation of age and haematoma volume in patients with spontaneous lobar intracerebral

haemorrhage. J Neurol Neurosurg Psychiatry 2011; 82:144.

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ADDITIONAL RECOMMENDATIONS .1• Rapid neuroimaging with CT /MRI is recommended to distinguish ischemic stroke from

ICH. (Class I; LOE-A)

• In patients presenting with a systolic BP of 150 to 220 mmhg ,acute lowering of SBP to 140 mmhg is prabably safe. (Class IIa; LOE-B)

• Prophylactic anticonvulsant medication shouldnot be used. (Class III; LOE-B)

• For patients with cerebellar hemorrhages >3 cm in diameter who are deteriorating or who have brainstem compression and/or hydrocephalus due to ventricular obstruction, it is recommended for surgical removal of hemorrhage. (Class I; LOE-B)

1. Broderick J, Connolly S, et al. Guidelines for the management of spontaneous intracerebral hemorrhage .A guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2010

Page 41: Spontaneous intracerebral hemorrhage

Thankyou

Note: References are included under each slides

Page 42: Spontaneous intracerebral hemorrhage

SURGERY

• For patients with cerebellar hemorrhages >3 cm in diameter who are deteriorating or who have brainstem compression and/or hydrocephalus due to ventricular obstruction, it is recommended for surgical removal of hemorrhage.

• Surgery for supratentorial ICH is controversial, and current guidelines suggest consideration of standard craniotomy only for those who have lobar clots within 1 cm of the surface.

• The routine evacuation of supratentorial ICH in the first 96 hours is not recommended.

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INTRAVENTRICULAR HEMORRHAGE

• Patients with intraventricular extension of the ICH are at risk for hydrocephalus, especially if the third and fourth ventricles are involved.

• Such patients should be closely monitored.

• When neurologic deterioration occurs, an emergent CT scan should be done to exclude the development of hydrocephalus.

• Patients with neurologic deterioration in the setting of ventricular enlargement may be candidates for ventriculostomy and external ventricular drainage.

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RESUMPTION OF ANTIPLATELET THERAPY• It is probably safe to resume therapy after the acute phase of ICH provided that

blood pressure is well controlled and that the indication for antiplatelet treatment is sufficiently strong that the potential benefit outweighs the increase in risk of recurrent ICH.

• The best available data comes from meta-analyses of randomized controlled trials; these suggest that aspirin use is associated with an approximately 40 percent relative increase in the risk of initial ICH, which translates into a very small absolute increase in risk [1,2).

• In the setting of cerebral amyloid angiopathy, aspirin use may be associated with a greater risk of recurrent ICH [3].

1. He J, Whelton PK, Vu B, Klag MJ. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA 1998; 280:1930.

2. Hart RG, Halperin JL, McBride R, et al. Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses. Arch Neurol 2000; 57:326.

3. Biffi A, Halpin A, Towfighi A, et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology 2010; 75:693.

Page 45: Spontaneous intracerebral hemorrhage

• Although aspirin reduces the risk of ischemic stroke by 25 percent, this benefit is largely negated by the associated increased risk of recurrent ICH, which typically causes more disability than ischemic stroke.

• Therefore, it is not recommended aspirin or anti-platelets for those patients with only an "average" risk of recurrent ischemic stroke.

• “Average" risk : HTN, DM, hypercholesterolemia, and the absence of heart disease .

• “Above Average" risk : Atrial fibrillation, cardiomyopathy, large vessel extracranial and intracranial stenoses, and malignancy :may benefit from long-term antiplatelet therapy after ICH.

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TIMING AND DOSE

• The timing of antiplatelet use after ICH is largely empiric. There is risk of rebleeding and hematoma expansion in the first several hours. At 10 days, rebleeding is unlikely.

• The AHA/ASA guidelines of 2006 state that antiplatelets should be discontinued for at least one to two weeks [1].

• If aspirin is used after ICH, a lower dose (30 to 160 mg daily) is both effective and safer than higher doses.

1. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 2006; 37:577.

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• End of slides


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