What antihypertensive (blood pressure lowering medication) to use in a patient with a large intracranial hemorrhage (ICH)?

From the Guidelines

For a large intracranial bleed with hypertension, I recommend using intravenous labetalol as the first-line agent to rapidly lower blood pressure to a target systolic BP of 140 mmHg, as it is the most recent and highest quality recommendation supported by the 2022 guideline from the American Heart Association/American Stroke Association 1. The choice of labetalol is based on its ability to be quickly titrated, have predictable effects, and minimally impact cerebral blood flow autoregulation.

• Labetalol can be given as 10-20 mg IV bolus followed by 20-80 mg every 10 minutes or as a continuous infusion at 0.5-2 mg/min.
• Blood pressure should be lowered gradually to prevent cerebral hypoperfusion, which could worsen neurological outcomes.
• Continuous arterial line monitoring is ideal for precise BP management. The 2022 guideline suggests that early intensive blood pressure lowering is safe and may be beneficial in reducing hematoma expansion and improving functional outcomes, as seen in the INTERACT2 trial 1.
• The guideline also recommends avoiding large fluctuations in blood pressure, as high systolic blood pressure variability during the hyperacute and acute phases of intracerebral hemorrhage is associated with poor outcomes.
• Other antihypertensive agents like nicardipine and clevidipine may also be used, but labetalol is the preferred agent due to its safety and efficacy profile, as supported by the 2019 ESC Council on Hypertension position document 1 and the 2015 Canadian Stroke Best Practice Recommendations 1.

From the FDA Drug Label

Labetalol beta1-receptor blockade in man was demonstrated by a small decrease in the resting heart rate, attenuation of tachycardia produced by isoproterenol or exercise, and by attenuation of the reflex tachycardia to the hypotension produced by amyl nitrite. In a clinical pharmacologic study in severe hypertensives, an initial 0. 25 mg/kg injection of labetalol HCl, administered to patients in the supine position, decreased blood pressure by an average of 11/7 mmHg.

Labetalol can be used to manage blood pressure in patients with severe hypertension, including those with large intracranial bleed, as it has been shown to decrease blood pressure without causing significant reflex tachycardia.

• The initial dose of labetalol is 0.25 mg/kg, which can be administered intravenously.
• The dose can be titrated to achieve the desired blood pressure reduction.
• It is essential to monitor blood pressure and heart rate closely during and after the infusion to avoid excessive reduction in blood pressure or tachycardia 2.

From the Research

Antihypertensive Options for Large Intracranial Bleed

• Nicardipine and labetalol are two commonly used antihypertensives for treating elevated blood pressures in the setting of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) 3, 4, 5.
• A study comparing clevidipine and nicardipine in patients with hemorrhagic stroke found no significant difference in time to goal systolic blood pressure (SBP) between the two groups 6.
• Nicardipine appeared to have similar efficacy as clevidipine in SBP reduction, with a more likely reduction of rebound hypertension and drug cost 6.
• Labetalol was found to have a shorter time to goal BP as compared to nicardipine in one study 4, but another study found that labetalol was associated with increased in-hospital infections compared with nicardipine 5.

Efficacy and Safety of Antihypertensives

• Both nicardipine and labetalol appear equally effective and safe for blood pressure control in SAH and ICH during the initial admission hours 3, 4.
• Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 hours in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events 7.
• The choice of antihypertensive may depend on individual patient factors, such as the presence of certain comorbidities or the risk of adverse events 5.

Comparison of Antihypertensives

• A systematic review and individual participant data analysis found that mean hourly systolic blood pressure during the initial 24 hours was positively associated with death or disability and hematoma expansion 7.
• Nicardipine had a higher total volume of infusion compared with clevidipine, but significantly lower cost 6.
• Labetalol was associated with a higher incidence of tachycardia compared to nicardipine, but the incidence of hypotension and bradycardia were similar 4.