What are the recommended drug doses and durations for the management of intraparenchymal hemorrhage?

Management of Intraparenchymal Hemorrhage: Drug Doses and Durations

Blood Pressure Management

For patients with intraparenchymal hemorrhage and elevated blood pressure, target a systolic blood pressure of 130-150 mmHg using continuous intravenous antihypertensive agents, with specific dosing protocols based on the degree of hypertension. 1

Blood Pressure Targets and Monitoring

• If SBP >200 mmHg or MAP >150 mmHg: Initiate aggressive blood pressure reduction with continuous intravenous infusion and monitor blood pressure every 5 minutes 1

• If SBP >180 mmHg or MAP >130 mmHg with evidence of elevated ICP: Monitor ICP and reduce blood pressure using intermittent or continuous IV medications to maintain cerebral perfusion pressure of 60-80 mmHg 1

• If SBP >180 mmHg or MAP >130 mmHg without elevated ICP: Target modest blood pressure reduction to MAP of 110 mmHg or target blood pressure of 160/90 mmHg using intermittent or continuous IV medications, with clinical re-examination every 15 minutes 1

• Optimal contemporary target: Aim for systolic blood pressure of 130-150 mmHg, as very intense and rapid blood pressure lowering below this threshold is potentially harmful 1

Specific Antihypertensive Drug Dosing

Nicardipine (preferred agent based on efficacy data):

• Continuous infusion: 5-15 mg/h 1
• No bolus dosing required 1
• Superior blood pressure control compared to labetalol, with 78% time within goal MAP versus 58% for labetalol 2

Labetalol:

• Bolus: 5-20 mg IV every 15 minutes 1
• Continuous infusion: 2 mg/min (maximum 300 mg/day) 1

Esmolol:

• Loading dose: 250 μg/kg IV push 1
• Continuous infusion: 25-300 μg/kg/min 1

Enalapril:

• Initial test dose: 0.625 mg IV (due to risk of precipitous blood pressure lowering) 1
• Maintenance: 1.25-5 mg IV every 6 hours 1

Hydralazine:

• Bolus: 5-20 mg IV every 30 minutes 1
• Continuous infusion: 1.5-5 μg/kg/min 1

Sodium nitroprusside:

• Continuous infusion: 0.1-10 μg/kg/min 1

Nitroglycerin:

• Continuous infusion: 20-400 μg/min 1

Duration of Intensive Blood Pressure Control

• Maintain intensive blood pressure monitoring and control for the first 24-72 hours after hemorrhage onset, as this is the period of highest risk for hematoma expansion 3, 4
• Continue blood pressure management beyond 72 hours based on clinical stability and risk of rebleeding 3

Anticoagulation Reversal

Warfarin-Associated ICH

Four-factor prothrombin complex concentrate (4F-PCC):

• Administer immediately when INR ≥2.0 1
• Dose based on INR and body weight (specific dosing per product labeling) 1

Vitamin K:

• Administer intravenously immediately after 4F-PCC to prevent later INR increase and associated hematoma expansion 1
• Dose: 10 mg IV 1

Direct Oral Anticoagulant (DOAC)-Associated ICH

Dabigatran:

• Idarucizumab (specific antidote): 5 g IV as two consecutive 2.5 g infusions 1
• If unavailable: (activated) prothrombin complex concentrate 1
• Hemodialysis may be considered for dabigatran removal 1

Factor Xa inhibitors (apixaban, edoxaban, rivaroxaban):

• Andexanet alfa (specific antidote) if available 1
• If unavailable: (activated) prothrombin complex concentrate 1

Heparin-Associated ICH

Unfractionated heparin or low-molecular-weight heparin:

• Protamine sulfate IV immediately 1
• Dose: 1 mg protamine per 100 units of heparin (for UFH) or per 1 mg of enoxaparin 1

Antiplatelet-Associated ICH

For patients on aspirin NOT scheduled for emergency surgery:

• Do NOT administer platelet transfusions - potentially harmful and should not be given 1

For patients on aspirin requiring emergency neurosurgery:

• Platelet transfusion might be considered to reduce postoperative bleeding and mortality (Class IIb recommendation) 1

For patients on antiplatelet agents (general):

• Desmopressin with or without platelet transfusions has uncertain effectiveness for reducing hematoma expansion 1

Hemostatic Therapy

Tranexamic Acid (TXA)

The effectiveness of TXA to improve functional outcome in spontaneous ICH is not well established, and routine use is not recommended. 1

• If considered in trauma-related hemorrhage context: 10-15 mg/kg loading dose followed by 1-5 mg/kg/h infusion 1
• For hemophilia patients (FDA-approved indication): 10 mg/kg IV 3-4 times daily for 2-8 days, infused no faster than 1 mL/minute 5

Recombinant Factor VIIa

The effectiveness of recombinant factor VIIa to improve functional outcome is unclear and is not routinely recommended. 1

• Phase III trial used 80 μg/kg dose within 4 hours of ICH onset, but showed no functional benefit despite limiting hematoma expansion 1
• Significant increase in arterial thrombotic events noted 1

Venous Thromboembolism Prophylaxis

Timing and Dosing

Subcutaneous low-molecular-weight heparin or unfractionated heparin:

• May be considered in patients with hemiplegia after 3-4 days from onset 1
• Specific dosing: prophylactic doses per institutional protocols (typically enoxaparin 40 mg SC daily or UFH 5000 units SC every 8-12 hours) 1

Inferior vena cava filter:

• Consider acute placement for patients who develop acute proximal venous thrombosis, particularly with clinical or subclinical pulmonary emboli 1

Long-Term Antithrombotic Therapy After VTE

• Decision to add long-term antithrombotic therapy several weeks or more after vena cava filter placement must consider the likely cause of hemorrhage (amyloid versus hypertension), associated arterial thrombotic risk conditions, and overall patient health and mobility 1

Intracranial Pressure Management

ICP Monitoring Indications

Consider ICP monitoring for patients with:

• Glasgow Coma Scale score ≤8 1
• Clinical evidence of transtentorial herniation 1
• Significant intraventricular hemorrhage or hydrocephalus 1

Target Parameters

• Maintain cerebral perfusion pressure of 50-70 mmHg depending on cerebral autoregulation status 1
• Treat ICP >20 mmHg 1

Ventricular Drainage

For hydrocephalus:

• Ventricular drainage is reasonable as treatment, especially in patients with decreased level of consciousness 1
• Insert ventricular catheter for both ICP monitoring and CSF drainage 1

Contraindicated Therapy

Corticosteroids:

• Should NOT be administered for treatment of elevated ICP in ICH 1

Critical Pitfalls to Avoid

• Never delay blood pressure control: Initiate treatment immediately upon diagnosis, as hematoma expansion occurs most commonly in the first 3-6 hours 3, 4

• Avoid excessive blood pressure lowering: Do not reduce systolic blood pressure below 130 mmHg, as this may be harmful 1

• Do not give platelet transfusions to non-surgical patients on aspirin: This is potentially harmful and associated with worse outcomes 1

• Infuse tranexamic acid slowly: Maximum rate of 1 mL/minute to avoid hypotension 5

• Correct coagulopathy before ICP monitor placement: Evaluate coagulation status and consider platelet transfusion or reversal agents before inserting monitoring devices 1