Update your INTRAcerebral Hemorrhage protocol

Use 4-factor prothrombin complex concentrate (Kcentra) for warfarin-related ICH when INR is 1.3 or higher....
Abdelwahab Ward, BS Pharm, PharmD

Introduction

As a hospital pharmacist, you will be asked about spontaneous intracerebral hemorrhage (ICH) treatment, due to updated guidelines. Follow these points...

Management approach

Anticoagulant reversal

Use 4-factor prothrombin complex concentrate (Kcentra) for warfarin-related ICH when INR is 1.3 or higher, along with IV vitamin K to reduce risk of INR rebound.

  • Lean toward Kcentra fixed doses for easier prep and lower cost. Efficacy seems similar to weight-based doses.
    • Consider giving 1,500 units, or possibly 2,000 units for patients weighing over 100 kg or with baseline INR over 7.5.
    • Don’t be surprised if some experts use lower doses for an INR less than 2.

Continue to use idarucizumab for dabigatran-related ICH. But for factor Xa inhibitors (apixaban, etc), use Kcentra, activated prothrombin complex concentrate (FEIBA) or andexanet alfa (Andexxa). There’s no proof one works best. Lean toward Kcentra or FEIBA due to easier prep and administration, and lower cost. Work with neurosurgery on when to restart anticoagulants. For example, consider around 8 weeks post ICH in patients with atrial fibrillation, limited data suggest this is the sweet spot. Think about earlier, such as 1 to 2 weeks, for patients with high clot risk (mechanical heart valves, etc).

Blood pressure lowering

For systolic blood pressure (SBP) below 220 mmHg, generally aim for a goal around 140 mmHg, and within 130 to 150 mmHg for at least 24 hours after ICH onset. But don’t overshoot, SBP below 130 mm Hg may worsen outcomes.

  • Consider starting antihypertensives in the first 2 hours of symptom onset, and trying to reach goal within an hour of starting.
  • For an initial SBP over 220 mmHg or severe ICH, such as blood volume 30 mL or more, collaborate with neurosurgery to individualize care.

You may need to decrease BP more conservatively. For all patients, focus on smooth titrations to avoid BP fluctuations. This may prevent hematoma growth and improve outcomes. For example, reduce nicardipine to about 3 mg/hr once at goal. Overshooting is common, due to a duration of at least 30 minutes.

Seizure prophylaxis

Generally don’t give antiseizure medications for prophylaxis, this doesn’t seem to affect outcomes in most patients. For more data, Get our notes, "Pharmacotherapy considerations on intracerebral hemorrhage", AND "Management of severe hypertension in adults".

References

  1. Greenberg SM, Ziai WC, et al. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-e361.
  2. Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Gluckman TJ, Hucker WJ, Mehran R, Messé SR, Perino AC, Rodriguez F, Sarode R, Siegal DM, Wiggins BS. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020 Aug 4;76(5):594-622.
  3. Moullaali TJ, Wang X, Martin RH, Shipes VB, Robinson TG, Chalmers J, Suarez JI, Qureshi AI, Palesch YY, Anderson CS. Blood pressure control and clinical outcomes in acute intracerebral haemorrhage: a preplanned pooled analysis of individual participant data. Lancet Neurol. 2019 Sep;18(9):857-864.
Abdelwahab Ward, BS Pharm, PharmD