Intracerebral%20hemorrhage Treatment

Elevated Blood Pressure Management

• Lowering blood pressure (BP) reduces the risk of rebleeding and may prevent expansion of the hematoma
  • Several studies have shown that treatment of intravenous (IV) Nicardipine or Labetalol in patients with intracerebral hemorrhage (ICH)-related acute hypertension that reduces SBP to 110-140 mmHg in the first 24 hours after ICH is well tolerated and associated with a reduced risk of hematoma expansion, neurological deterioration, and in-hospital mortality
• Patients with mean arterial pressure (MAP) ≥130 mmHg may receive IV or per orem (PO) antihypertensives
• If BP is lowered too rapidly, cerebral perfusion pressure (CPP) may drop and cause brain injury especially if intracranial pressure is increased
• In patients with high BP and suspected high intracranial pressure on CT scan, monitor continuously intracranial pressure, BP and CPP
• Acute lowering of systolic blood pressure to 140 mmHg, in patients with small- to moderate-size, non-surgical ICH presenting with systolic blood pressure of 150-220 mmHg, may be considered safe and can be effective for improving functional outcome
• Aggressive reduction of blood pressure with a continuous antihypertensive IV infusion and frequent ICH may be considered in patients presenting with systolic blood pressure of >220 mmHg

Reference: 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.


Low Blood Pressure Management

Volume Replenishment

• 1st-line therapy to treat low BP in stroke patient
• Monitor with central venous pressure (CVP) or pulmonary wedge pressure

Phenylephrine, Dopamine or Norepinephrine

• May be used if volume replacement fails to correct hypotension

• Discontinue immediately all anticoagulants and antiplatelets after the onset of intracerebral hemorrhage (ICH) and reverse the anticoagulation effect with appropriate agents; however, carefully weigh the risk of bleeding against the risk of thrombosis if anticoagulation is stopped or reversed
• Prothrombin complex concentrate, factor IX complex concentrate, fresh frozen plasma (FFP) and recombinant activated factor VII (rFVIIa) normalize the laboratory elevation of the international normalized ratio (INR) very rapidly
• Treat patients with severe coagulation factor deficiency with appropriate factor replacement
• Patients with thrombocytopenia and severe coagulation factor deficiency should receive platelet transfusion
  • Platelet transfusion should be avoided in patients on antiplatelet therapy as outcome may be adversely affected, though it can be done in patients scheduled for surgical evacuation of hematoma
• It is recommended that patients with elevated INR, due to intake of oral anticoagulants, should stop warfarin, replace vitamin K-dependent factors, correct INR, and start IV vitamin K
• Decision to restart antithrombotic therapy after ICH related to antithrombotic therapy depends on the risk of subsequent arterial or venous thromboembolism, the risk of recurrent ICH, and the overall state of the patient
  • After confirming bleeding cessation, low-dose subcutaneous unfractionated Heparin or low-molecular-weight Heparin may be started after 1-4 days of onset to prevent deep venous thrombosis in immobile patients

Prothrombin Complex Concentrates (PCC)

• Recommended intervention to reverse life-threatening anticoagulant-associated bleeding in adults with ICH that occurred during treatment with vitamin K antagonists (VKA) and with INR above normal
• Four-factor PCC may be considered to reverse the anticoagulant effect in adults with ICH that occurred during treatment with a non-vitamin K oral anticoagulant (NOAC) in the absence of other agents
• Advantages: Rapid reconstitution and administration, high concentration of coagulation factors (eg II, VII, IX and X) in small volume, and less infections

Fresh Frozen Plasma (FFP)

• Limited by risk of allergy, infection, processing time and volume required for correction
• May be considered for reversal of the anticoagulant effect of Warfarin in adults with ICH that occurred during treatment in case of unavailability of PCC
• Should not be used to reverse the effects of a NOAC in patients with ICH that occurred during treatment

Vitamin K

• Adjunct therapy to oral anticoagulant-associated hemorrhages in adults with INR ≥3 with ICH that occurred during treatment with VKA

Recombinant Activated Factor VII (rFVIIa)

• Can rapidly normalize INR in NOAC-associated hemorrhages but does not replace all clotting factors and has not been shown to improve functional outcome 
• Treatment option for patients ≤70 years of age with baseline ICH volume <60 mL, intraventricular hemorrhage volume <5 mL and time from onset-to-treatment ≤2.5 hours
• Not recommended as routine treatment for Warfarin reversal

Andexanet alfa

• Recommended intervention to reverse the anticoagulant effect of Apixaban, Edoxaban, Rivaroxaban or low-molecular-weight Heparin (eg Enoxaparin, Dalteparin, Nadroparin, Tinzaparin) in adults with ICH that occurred during treatment

Idarucizumab

• Recommended intervention to reverse the anticoagulant effect of Dabigatran in adults with ICH that occurred during treatment

Tranexamic acid

• A hemostatic agent that may be considered for use in patients with spontaneous ICH and a possible intervention to reverse direct NOAC-associated bleeding because of a reduction in early deaths and serious adverse events but no improvement in functional outcome
• Should not be used in patients with ICH that occurred during treatment with VKA and with INR ≥1.3

Protamine sulfate

• Used to reduce bleeding tendency in patients with Heparin-associated ICH, with the dose depending on the dose of Heparin and the time since Heparin has been given

Other Agents

• Other hemostatic agents currently undergoing clinical trials include Ciraparantag and Desmopressin

• Elevated ICP is >20 mmHg for >5 minutes
• Goal ICP is <20 mmHg and cerebral perfusion pressure (CPP) 50-70 mmHg
• Monitor ICP using ventricular catheter
• ICP monitoring may be considered in the following patients: Glasgow Coma Scale (GCS) score of <8, clinical evidence of transtentorial herniation, significant intraventricular hemorrhage, and hydrocephalus
• Treatment should include a balanced and graded approach beginning with simple measures to more aggressive therapies
• Recommended step-by-step approach for ICP >20-25 mmHg:
  • Cerebrospinal fluid (CSF) drainage
  • Mannitol or hypertonic saline bolus
  • Sedation
  • Neuromuscular blockade
  • Consider mild hyperventilation
  • Hypothermia, hemicraniectomy, barbiturate coma

• Consider repeat computed tomography (CT) scan if ICP is still >20-25 mmHg
• Withdraw ICP therapies once ICP is <20 mmHg

Head-of-Bed Elevation

• Keep head of bed elevated at 30^° with patient’s neck in neutral position to maximize venous outflow, lowering ICP

Analgesia and Sedation

• Titrate to minimize pain and increase in ICP while allowing evaluation of clinical status
  • Can be achieved with IV Propofol, Etomidate, or Midazolam for sedation and Morphine or Alfentanil for analgesia

Cerebrospinal Fluid (CSF) Drainage

• Effective especially in the setting of hydrocephalus
• Used when an intraventricular catheter is in place to monitor ICP

Osmotic Therapy

• Target serum osmolality: 300-320 mOsm/kg
• Should only be used in patients with type B ICP waves, progressively increasing ICP waves or clinical deterioration associated with mass effect
• Mannitol is the most commonly used intravenous (IV) osmotic agent
  • Produces lowering of ICP within 20 minutes of administering an IV bolus
• Furosemide may be administered simultaneously to maintain osmotic gradient
• Hypertonic saline solutions have been shown to reduce ICP, even in cases refractory to hyperventilation and Mannitol

Neuromuscular Blockade

• Used with sedation and/or analgesia to prevent elevated ICP due to increased intrathoracic pressure and obstruction in cerebral venous outflow
• Nondepolarizing agents: Eg Vecuronium or Pancuronium

Hyperventilation

• One of the most effective methods to rapidly reduce ICP 
  • Reserved for use as a temporizing measure while awaiting more definitive treatments
• Reduction of PaCO₂ to 30–35 mmHg lowers ICP by 25-30% in most patients
• ICP reduction may take up to 30 minutes to occur after PaCO₂ is changed
•  Failure of ICP to respond to hyperventilation indicates a poor prognosis

Barbiturate Coma

• Depresses cerebral metabolic activity which reduces cerebral blood flow and ICP
• Barbiturates effectively reduce brain swelling
  • Eg Pentobarbital, Thiopental
  • Safe limit ≈10 mg/kg/day

Elevated Glucose

• High blood glucose on admission predicts an increased fatality rate in both non-diabetic and diabetic patients with intracerebral hemorrhage (ICH)
• Monitoring of glucose level is important; normoglycemia should be maintained
• Hypoglycemia and hyperglycemia should be avoided

Seizures

• The majority of seizures occur within the 1st 24 hours of ICH onset
• Clinical (or proven subclinical) seizures or patients with a change in mental status with electrographic seizures on electroencephalography (EEG) should be treated with antiepileptic drugs
• Continuous electroencephalography monitoring may be indicated in patients with depressed mental status that is disproportionate to the degree of brain injury
• Anticonvulsant can usually be discontinued after 1 month in patients who do not suffer from further seizures
  • Long-term treatment with anticonvulsant may be necessary if patients experience seizures >2 weeks after ICH
• Prophylactic treatment is not recommended

Body Temperature

• Fever (temperature >38.5°C) is a common occurrence in patients with ICH and increased fever duration is associated with poor outcomes
• Fever should be aggressively treated even as appropriate testing for systemic infection is being undertaken
  • May use cooling blankets and Paracetamol [intravenous (IV)/per orem (PO)/rectal]

Other General Measures

• Fluid management, nutrition, and prevention of aspiration pneumonia and bed sores are the same as for patients with ischemic stroke
  • Use normal saline for fluid replacement and maintenance, avoid hypotonic fluids
• Use of intermittent pneumatic compression with elastic stockings is advised to prevent deep venous thrombosis 
• Prophylactic administration of H₂ blockers or drugs that can protect the mucosa decreases the incidence of gastric hemorrhage; routine use should be avoided due to increased risk of hospital-acquired pneumonia and enteric infections
• It is generally recommended to do full aggressive care early (ie the 1st day) after ICH onset and postponement of new do-not-resuscitate (DNR) orders until at least the 2nd full day of hospitalization