According to 2019 and 2018 American Heart Association (AHA)/American Stroke Association (ASA) guidelines for the management of patients with acute ischemic stroke, it is recommended to maintain blood pressure at ≤ 180/105 mm Hg during and after alteplase or other acute reperfusion therapy. Blood pressure measurements and neurological assessments should be conducted every 15 minutes during and after intravenous (IV) alteplase infusion for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours after IV alteplase treatment. The frequency of blood pressure measurements should be increased if systolic blood pressure is > 180 mm Hg or if diastolic blood pressure is > 105 mm Hg, and antihypertensive medications should be administered to maintain the blood pressure at or below these levels using the same recommended agents that are used to lower the blood pressure prior to IV alteplase administration. A list of these agents with their respective dosing recommendations is provided in Table 1; labetalol, nicardipine, or clevidipine are recommended, and other agents, including hydralazine and enalaprilat, may also be considered. There does not appear to be a preference for one agent over the other. If the patient develops severe headache, acute hypertension, nausea, or vomiting or has a worsening neurological examination, the IV alteplase infusion should be discontinued, and an emergency head computed tomography (CT) scan should be obtained. [1], [2]
A 2019 review discusses blood pressure management during and after recanalization therapy for acute ischemic stroke. In general, agents with a fast onset of action and short duration are preferable in the acute setting to rapidly achieve hemodynamic goals and avoid prolonged periods of hypotension. Each agent has various contraindications and may be useful in specific clinical scenarios based on patients' comorbidities. Agents recommended for blood pressure-lowering during and after recanalization therapy for acute ischemic stroke include labetalol, hydralazine, enalaprilat, nicardipine, clevidipine, sodium nitroprusside, or nitroglycerin (see Table 1 for respective dosing and administration recommendations, pharmacokinetics, and clinical pearls). [3]
Labetalol, which has negative chronotropic effects, may limit its utility in patients with significant bradycardia. However, it is a suitable agent for patients with acute ischemic stroke or other intracranial pathology, given its minimal impact on either cerebral blood flow or oxygen consumption. Nicardipine allows for a faster and more controlled reduction in blood pressure with significantly less variability compared to labetalol; however, head-to-head studies have found no differences in clinical outcomes between the two agents and the cost associated with nicardipine therapy is substantially higher. Like nicardipine, clevidipine generally does not decrease heart rate and has similar efficacy in lowering blood pressure. As less volume is required for clevidipine administration, it may be optimal in patients with volume overload. Since clevidipine is formulated in a lipid emulsion, there is an inherent risk of hypertriglyceridemia and pancreatitis, and the maximum daily dose is 1,000 mL (or approximately 21 mg/hour/day). [3]
Despite hydralazine's effectiveness in lowering blood pressure, it can increase intracranial pressure while simultaneously reducing mean arterial pressure, leading to decreased perfusion pressure and increasing the risk of ischemia. Additionally, hydralazine has a prolonged and often unpredictable effect on blood pressure, leading to steep drops in pressure and significant variability. Therefore, hydralazine is less preferred in acute ischemic stroke but can be considered when other agents are unavailable. Angiotensin-converting enzyme inhibitors such as enalaprilat are thought to be neutral for intracranial pressure, making it a potential option in patients with intracranial pathology; however, its long duration of action (i.e., 12-24 hours) limits the ability to titrate the agent to specific blood pressure goals. Additionally, there is an increased risk of orolingual angioedema during alteplase administration. [3]
Due to the vasodilatory effects on cerebral vasculature with sodium nitroprusside, increased intracranial pressure can occur in patients with impaired autoregulation. Sodium nitroprusside also contains cyanide, which can accumulate and lead to toxicity. Patients at risk for cyanide toxicity include those with hypoalbuminemia or those undergoing cardiopulmonary bypass. Despite its potent anti-hypertensive properties, sodium nitroprusside is a less ideal agent for use in acute ischemic stroke due to its potential for impacting cerebral blood volume and intracranial pressure. However, it can be considered in cases where other agents are not available or are contraindicated due to patient-specific characteristics. Nitroglycerin has been found to be effective in lowering blood pressure but not functional outcomes in acute ischemic stroke, but similar to sodium nitroprusside, it may increase intracranial pressure based on limited observational studies. In accordance with guideline recommendations, the authors appear to prefer nicardipine, labetalol, or clevidipine over other recommended agents, such as hydralazine, enalaprilat, sodium nitroprusside, or nitroglycerine for blood pressure management during and after recanalization with alteplase, but the preferred agent should depend on patient-specific factors and comorbidities. [3]
A 2014 review discusses blood pressure management in acute ischemic stroke and intracerebral hemorrhage. Blood pressure agents should be rapid-acting, easily titrated, and have few side effects and short half-lives. Commonly used IV medications include nicardipine, labetalol, sodium nitroprusside, nitroglycerin, enalaprilat, and hydralazine. Due to the unpredictable dose-response relationship, risk of rebound hypertension, possibility of cyanide toxicity during prolonged use, and potential to cause raised intracranial pressure, sodium nitroprusside may not be ideal for acute reduction of blood pressure. Additionally, while hydralazine is used frequently for acute reduction of BP, its use in routine clinical practice is limited due to its selective arteriolar vasodilator effect, resulting in reflex tachycardia leading to myocardial injury. Data comparing the therapeutic response and tolerability of labetalol boluses versus IV nicardipine infusion in the acute stroke setting demonstrated a higher proportion of patients receiving nicardipine achieved goal blood pressure within 60 minutes of treatment initiation (100% vs. 61%; p<0.001) and spent a greater amount of time in the goal blood pressure range compared to the labetalol group. Additionally, the number of dose adjustments required to reach goal blood pressure was lower (0 vs. 2, p<0.001) in the nicardipine group, which indicates a reliable dose-response. [4], [5]
Three retrospective cohort studies compared clevidipine and nicardipine for acute blood pressure reduction in patients with stroke, including both ischemic and hemorrhagic strokes. Time to achieve blood pressure goal, which was the primary outcome across all three studies, was not significantly different between nicardipine- and clevidipine-treated groups. Other efficacy and safety outcomes were similar between the two agents, except that in one study, clevidipine administration resulted in significantly less volume administered per patient versus nicardipine. Overall, both agents are reasonable options for blood pressure management during acute stroke, even though cost and volume restriction could differentiate preference. Results from retrospective studies need to be interpreted with caution, as confounding factors, such as inconsistent charting of blood pressure during an emergency, cannot be completely ruled out. [6], [7], [8]