Benjamin Anyanwu,MD Medical Director In-patient Neurology and Neuroscience ICU Novant Health Forsyth Medical Center, Winston-Salem NC

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1 Benjamin Anyanwu,MD Medical Director In-patient Neurology and Neuroscience ICU Novant Health Forsyth Medical Center, Winston-Salem NC

2 Emergency Treatment of Hemorrhagic Stroke

3 Objectives Discuss the etiology of spontaneous intracerebral hemorrhage (sich) and hemorrhagic stroke Discuss the emergency assessment and evaluation of patients presenting with sich Provide an overview of the emergency management of patients presenting with sich Discuss the factors that predict morbidity and mortality of sich patients

4 Background 13% 87% Circulation. 2012; 125(1):e2-220.

5 Background Spontenous Intracerebral hemorrhage (sich) distinct from extra axial intracranial hemorrhage

6 Background Extra-axial

7 Background Intracerebral Hemorrhage (Stroke)

8 Clinical Presentation The abrupt onset of focal neurological symptoms Headaches Nausea and Vomiting (3x) Elevated BP, severe headache, coma or decreased level of consciousness, and progression over minutes or hours all suggest ICH; although non-specific

9 Etiology Uncontrolled Hypertension Oral Anticoagulation Treatment (OAC-ICH) Vascular Malformations (AVM, Dural Fistulas etc) Tumors (Primary brain tumors/metastatic brain tumors) Venous Hemorrhage ( Cerebral venous sinus thrombosis) Vasculitis Amyloid angiopathy Illicit drug abuse (Sympathomimetics) Trauma ( direct, indirect)

10 Initial Evaluation : Locations of ICH Basal Ganglia (50%) Lobar regions (10-15%) Thalamus (10-15%) Pons (13-15%) Cerebellum (10%) Tumors that Bleed: CT-MR. Lung Ca by number

11 Etiology Population-based studies show that most patients present with small ICHs that are readily survivable with good medical care Suggests that excellent medical care likely has a potent, direct impact on ICH morbidity and mortality Outcome dependent on appropriate evidence-based care AHA Guidelines for the Management of Spontaneous Intracerebral Hemorrhage Novant Health: Enter Presentation Title in Footer Menu

12 Initial Evaluation : Pre-hospital Intracranial hemorrhage is a medical emergency. Requires rapid diagnosis (clinical presentation similar to ischemic stroke) Early deterioration is common in the first few hours after onset. More than 20% of patients will experience a decrease in the Glasgow Coma Scale (GCS) score High rate of poor long-term outcomes underscore the need for aggressive early management Rapid transport to the nearest ED (call 911) Provide cardiovascular and air-way support if needed Information about medical history, medications and drug use Advance notification of ED demonstrated to significantly shorten time to computed tomography (CT) scanning in the ED

13 Initial Evaluation : Emergency Department Every ED should be prepared to treat patients with ICH or have a plan for rapid transfer to a tertiary care center. CT : gold standard; vs GRE T2* (consider contrast-enhanced or vascular imaging) Laboratory studies CXR, EKG NIHSS/ICH Score (Severity Score) Airway, respiration, blood pressure and signs of raised ICP Head of bed at 30 degrees / Osmotic diuretic / pco mmHg Elevated BP in 46% 56% of patients with ICH. (Dandapani et al 1995) Admit in Neuro ICU: Prolonged patient stays in the ED may lead to worse outcomes, although early neurocritical care management in the ED may ameliorate this effect.

14 Initial Evaluation: ICH Score / NIHSS METHODS: Records of all patients with acute ICH presenting to the University of California, San Francisco during were reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the ICH Score) was developed with weighting of independent predictors based on strength of association. RESULTS: Factors independently associated with 30-day mortality were Glasgow Coma Scale score (P<0.001), Age >/=80 years (P=0.001), Infratentorial origin of ICH (P=0.03), ICH volume (P=0.047), and presence of Intraventricular hemorrhage (P=0.052). The ICH Score was the sum of individual points assigned as follows: GCS score 3 to 4 (=2 points), 5 to 12 (=1), 13 to 15 (=0); age >/=80 years yes (=1), no (=0); infratentorial origin yes (=1), no (=0); ICH volume >/=30 cm(3) (=1), <30 cm(3) (=0); and intraventricular hemorrhage yes (=1), no (=0) The ICH score: a simple, reliable grading scale for intracerebral hemorrhage.( Hemphill JC 3rd,et al Stroke 2001 Apr;32(4):891-7)

15 Initial Evaluation : Hematoma Expansion Hematoma expansion ; 28% to 38% within first 3 hrs (Brott T, Broderick J, et al: Early hemorrhage growth in patients with intracerebral hemorrhage.stroke 1997 ) Uncontrolled Hypertension Oral Anticoagulation or Antiplatelet therapy ( Prasugrel :Effient, Ticagrelor:Brilinta) Severe coagulation factor deficiency or severe thrombocytopenia Spot Sign (Wada R et al CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage : Stroke 2007)

$Initial Evaluation : Penumbra Area at risk but salvageable: increase in oxygen extraction fraction (OEF)$

17 Initial Evaluation : Penumbra Area at risk but salvageable: increase in oxygen extraction fraction (OEF) followed by local tissue acidosis and eventually cell death. 17 Novant Health: Enter Presentation Title in Footer Menu

18 Initial Evaluation : Penumbra 18 Novant Health: Enter Presentation Title in Footer Menu

19 Initial Evaluation: Blood Pressure management Theoretically could contribute to hematoma expansion, peri-hematoma edema, and rebleeding. Autoregulation Measurement of systolic BP above 140 to 150 mm Hg within 12 hours of ICH is associated with poor outcome (Zhang Y et al :Blood pressure and clinical outcome among patients with acute stroke in Inner Mongolia, China. J. Hypertension 2008) No consensus

20 Initial Evaluation: Blood Pressure management INTERACT :INTensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (Anderson CS, Huang Y et al; INTERACT Investigators. Intensive blood pressure reduction in acute cerebral hemorrhage trial (INTERACT): a randomized pilot trial. Lancet Neurology 2008) 404 patient : Half to target a low systolic BP goal of 140 mm Hg within 1 hour and maintained for at least the next 24 hours, and the other to a systolic BP target of 180 mm Hg. Showed a trend toward lower relative and absolute growth in hematoma volumes from baseline to 24 hours in the intensive treatment group compared with the control group. Provides an important proof of concept for early BP lowering in patients with ICH, but the data are insufficient to recommend a definitive policy

21 Initial Evaluation: Blood Pressure management ATACH : Antihypertensive Treatment in Acute Cerebral Hemorrhage trial (Qureshi A. Antihypertensive treatment of acute cerebral hemorrhage (ATACH) trial. Presented at the International Stroke Conference, New Orleans, La, February 20 22, 2008) Used a 4-tier, dose escalation of intravenous nicardipine-based BP lowering in 80 patients with ICH Confirms the feasibility and safety of early rapid BP lowering in ICH ATACH-II is a five (5) year, multi-center, randomized, controlled, Phase-III trial with blinded study to determine the efficacy of early, intensive antihypertensive treatment using intravenous nicardipine for acute hypertension in subjects with spontaneous supratentorial ICH. *NH Forsyth Medical Center

22 INTERACT-2 Craig S. Anderson, M.D., Ph.D et al, NEJM May 29, 2013 Background: Whether rapid lowering of elevated blood pressure would improve the outcome in patients with ICH. Methods : 2839 patients who had had a sich within the previous 6 hours (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) Results: 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (OR with intensive treatment, 0.87; 95%, [CI], 0.75 to 1.01; P=0.06) Conclusions : In patients with sich, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of mrs indicated improved functional outcomes with intensive lowering of blood pressure

23 Initial Evaluation: Blood Pressure management For ICH patients presenting with SBP between 150 and 220 mm Hg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mm Hg is safe (Class I; Level of Evidence A) and can be effective for improving functional outcome (Class IIa; Level of Evidence B) For ICH patients presenting with SBP >220 mm Hg, it may be reasonable to consider aggressive reduction of BP with a continuous intravenous infusion and frequent BP monitoring (Class IIb; Level of Evidence C) 23 Novant Health: Enter Presentation Title in Footer Menu

24 Initial Evaluation: Hemostasis/Antiplatelets Patients at risk include those on oral anticoagulants (OACs), acquired or congenital coagulation factor deficiencies, and those with qualitative or quantitative platelet abnormalities ( ETOH abuse, Liver disease ) Rapid recognition of an underlying coagulopathy Vitamin K intravenous Fresh Frozen Plasma Factor IX concentrate (PCC): contains factors II, VII, and X in addition to IX ( 3-factor vs 4-factor) rfviia: can limit the extent of hematoma expansion. Not recommended for VKA reversal in ICH

25 Initial Evaluation: Hemostasis/Antiplatelets 25 Novant Health: Enter Presentation Title in Footer Menu

26 Case 1 55yoM Presented to NHKMC INR 16.5 Vitamin K 2.5 PO Transferred to FMC INR 15.8 at NHFMC 21 minutes later order for Kcentra Kcentra administered 33 minutes later INR min after administration

27 Initial Evaluation: Hemostasis/Antiplatelets Usefulness of platelet transfusions in ICH patients with a history of antiplatelet use is uncertain (Class IIb; Level of Evidence C) For patients with ICH who are taking dabigatran, rivaroxaban, or apixaban, treatment with PCCs, or rfviia might be considered on an individual basis Activated charcoal might be used if the most recent dose of dabigatran, apixaban, or rivaroxaban was taken <2 hours earlier. Hemodialysis might be considered for dabigatran (Class IIb; Level of Evidence C) 27 Novant Health: Enter Presentation Title in Footer Menu

28 Initial Evaluation: Hemostasis/Antiplatelets RE-VERSE AD A Phase III Case Series Clinical Study of the Reversal of the Anticoagulant Effects of Dabigatran by Intravenous Administration of 5.0g Idarucizumab (BI ) in Patients Treated Wtih Dabigatran Etexilate Who Have Uncontrolled Bleeding or Require Emergency Surgery or Procedures 28 Novant Health: Enter Presentation Title in Footer Menu

29 Inpatient Management: Prevention of Secondary Brain Injury AHA Recommendation: Initial monitoring and management of ICH patients should take place in an intensive care unit or dedicated stroke unit with physician and nursing neuroscience intensive care expertise (Class I; Level of Evidence: B).

30 Inpatient Management : Nursing Patient positioning To minimize ICP and reduce the risk of ventilator-associated pneumonia in mechanically ventilated patients, the head should be elevated 30 degrees

31 Inpatient Management: Fluid therapy Isotonic fluids such as 0.9% saline Optimized to achieve euvolemic balance Maintained by monitoring fluid balance and body weight (Strict I/O) Avoid fluid overload, pulmonary edema, hypokalemia, cardiac arrhythmias, hyperchloremic metabolic acidosis, and dilutional coagulopathy

32 Avoid Hypotonic fluids

33 Inpatient Management: Nutrition Perform a swallow evaluation Choose appropriate diet based on co-morbidities Enteral feeding should be started within 48 hours to avoid protein catabolism and malnutrition. Small-bore naso-duodenal feeding tube may reduce the risk of aspiration Watch for micro-aspiration

34 Inpatient Medical Management :Management of Glucose Increased risk of mortality and poor outcome in patients with and without diabetes and ICH Improved outcomes with tight glucose control (range 80 to 110 mg/dl) using insulin infusions in mainly surgical critical care patients Glucose should be monitored and normoglycemia is recommended (Class I: Level of Evidence: C). Kimura K, et al :Hyperglycemia independently increases the risk of early death in acute spontaneous intracerebral hemorrhage. Neurol Sci: 2007 Van den Berghe G et al: Intensive insulin therapy in the critically ill patients. NEJM 2001

35 Inpatient Medical Management: Seizures The 30-day risk for convulsive seizures after ICH is approximately 8%, and the risk of overt status epilepticus is 1% to 2% The risk of late seizures or epilepsy among survivors of ICH is 5% to 27% Clinical seizures or electrographic seizures in patients with a change in mental status should be treated with antiepileptic drugs Prophylactic anticonvulsant medication should not be used (Class III; Level of Evidence: B) Passero S et al :Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia 2002, 43: Claassen J, Jetté N, Chum F, Green R, Schmidt M, Choi H, Jirsch J, Frontera JA, Connolly ES, Emerson RG, Mayer SA, Hirsch LJ: Electrographic seizures and periodic discharges after intracerebral hemorrhage

36 Inpatient Management: DVT prophylaxis High risk for deep vein thrombosis and pulmonary embolism Patients with ICH should have intermittent pneumatic compression for prevention of venous thromboembolism in addition to elastic stockings (Class I; Level of Evidence: B) After documentation of cessation of bleeding, low-dose subcutaneous low-molecular-weight heparin or unfractionated heparin may be considered for prevention of venous thromboembolism in patients with lack of mobility after 1 to 4 days from onset (Class IIb; Level of Evidence: B) Systemic anticoagulation or IVC filter placement is probably indicated in ICH patients with symptomatic DVT or PE (Class IIa; Level of Evidence C)

37 Inpatient Management : Fever Fever worsens outcome in experimental models of brain injury In patients surviving the first 72 hours after hospital admission, the duration of fever is related to outcome and appears to be an independent prognostic factor in these patients Concept of infectious versus central fever often challenging Michenfelder JD et al: The relationship among canine brain temperature, metabolism, and function during hypothermia. Anesthesiology 1991 Schwarz S et al; Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology 2000 Effectiveness of a Procalcitonin-Guided Algorithm to Differentiate Infectious from Non-Infectious Fever in Neurocritical Care. Christina Roels et al

38 Inpatient Management :Intraventricular Hemorrhage IVH occurs in 45% of patients with sich Primary Secondary Placement of EVD

transtentorial herniation, or those with significant IVH or

39 Inpatient Management :Intraventricular Hemorrhage Patients with a GCS score of 8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus might be considered for ICP monitoring and treatment.

40 Inpatient Management: Surgical Intervention CLEAR-IVH trial (Clot Lysis: Evaluating Accelerated Resolution of IVH) 100 patients (22 placebo, 78 rtpa) with IVH attributable to spontaneous ICH <30 mm 3 Bacterial ventriculitis occurred in 3 patients with rtpa (4%) and 2 with placebo (9%). Patients treated with rtpa had significantly lower intracranial pressures, fewer EVD obstructions that required replacement, and nonsignificantly shorter duration of EVD requirement There was symptomatic rebleeding in 9 rtpa patients (12%) and 1 patient given placebo (5%; P=0.33). Permanent CSF diversion was required in 14% of placebo and 6% of rtpa patients (P=0.27) Median 30-day modified Rankin scale score was 5 in both groups, and mortality was 19%, with no significant difference between placebo and rtpa 40 Novant Health: Enter Presentation Title in Footer Menu

41 Inpatient Management :Intraventricular Hemorrhage Although intraventricular administration of recombinant tissue-type plasminogen activator in IVH appears to have a fairly low complication rate, efficacy and safety of this treatment is uncertain and is considered investigational (Class IIb; Level of Evidence: B) 41 Novant Health: Enter Presentation Title in Footer Menu

42 Inpatient Management : Cerebral edema 42 Novant Health: Enter Presentation Title in Footer Menu

43 Inpatient Management : Cerebral edema Hypertonic saline ICP <20 mm Hg and a CPP of 50 to 70 mm Hg Mannitol Barbiturates Analgesia and Paralytics Corticosteroids should not be administered for treatment of elevated ICP in ICH (Class III; Level of Evidence B) 43 Novant Health: Enter Presentation Title in Footer Menu

44 Inpatient Management: Surgical Intervention The Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for ICH Evacuation Trial II (MISTIE II) Aimed to determine the safety of minimally invasive surgery plus rtpa in the setting of ICH Compared 79 surgical patients with 39 medical patients. The study demonstrated a significant reduction in perihematomal edema in the hematoma evacuation group with a trend toward improved outcomes (MISTIE III) : A randomized phase 3 clinical trial of minimally invasive hematoma evacuation is currently in progress. 44 Novant Health: Enter Presentation Title in Footer Menu

45 Mendelow AD et al: Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral hematomas (STICH II): a randomized trial. Lancet May 2013 Early surgery compared with initial conservative treatment could improve outcome in these patients Method: ( 78 centers in 27 countries ) Compared early surgical hematoma evacuation within 12 h of randomization plus medical treatment with initial medical treatment alone FINDINGS: 307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavorable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3 7% [95% CI -4 3 to 11 6], odds ratio 0 86 [0 62 to 1 20]; p=0 367). INTERPRETATION: The STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral hemorrhage without intraventricular hemorrhage.

46 Inpatient Management: Surgical Intervention For most patients with supratentorial ICH, the usefulness of surgery is not well established (Class IIb; Level of Evidence A). A policy of early hematoma evacuation is not clearly beneficial compared with hematoma evacuation when patients deteriorate (Class IIb; Level of Evidence A) Supratentorial hematoma evacuation in deteriorating patients might be considered as a life-saving measure (Class IIb; Level of Evidence C) DC with or without hematoma evacuation might reduce mortality for patients with supratentorial ICH who are in a coma, have large hematomas with significant midline shift, or have elevated ICP refractory to medical management (Class IIb; Level of Evidence C) The effectiveness of minimally invasive clot evacuation with stereotactic or endoscopic aspiration with or without thrombolytic usage is uncertain (Class IIb; Level of Evidence B) 46 Novant Health: Enter Presentation Title in Footer Menu

47 Inpatient Management: Surgical Intervention Cerebellar Hemorrhage Comprises 10% to 15% of cases

Inpatient Management: Surgical Intervention Patients with cerebellar hemorrhage who are deteriorating neurologically or who have brainstem compression and/or hydrocephalus from ventricular

48 Inpatient Management: Surgical Intervention Patients with cerebellar hemorrhage who are deteriorating neurologically or who have brainstem compression and/or hydrocephalus from ventricular obstruction should undergo surgical removal of the hemorrhage as soon as possible (Class I; Level of Evidence: B) Initial treatment of these patients with ventricular drainage alone rather than surgical evacuation is not recommended (Class III; Level of Evidence: C)

49 Inpatient Management: Cerebral Sinus Thrombosis

Inpatient Management: Cerebral Sinus Thrombosis Accounts for about < 2% of all Strokes Young adults 61% of females in the 20-35 age group

50 Inpatient Management: Cerebral Sinus Thrombosis Accounts for about < 2% of all Strokes Young adults 61% of females in the age group 50% of stroke during pregnancy Hypercouagulable state Dehydration Headaches, Focal neurological signs, Seizures Anticouagulation (Heparin)

51 When everything else has failed..

52 Inpatient Medical Management: Outcome Prediction Intracerebral hemorrhage Score (ICH-Score) Pre-existing Code Status Most patients that die from ICH do so during the initial acute hospitalization, and these deaths usually occur in the setting of withdrawal of support due to presumed poor prognosis. Aggressive full care early after ICH onset and postponement of new DNR orders until at least the second full day of hospitalization is probably recommended (Class IIa; Level of Evidence: B). Patients who are given DNR status at any point should receive all other appropriate medical and surgical interventions unless otherwise explicitly indicated

53 Thank You

Modern Management of ICH

Modern Management of ICH Bradley A. Gross, MD Assistant Professor, Dept of Neurosurgery, University of Pittsburgh October 2018 ICH Background Assessment & Diagnosis Medical Management Surgical Management