Today’s episode topic is being presented at the request of another “Pharmacy Joe” who left a voice message on pharmacyjoe.com about using clonidine for hypertensive emergencies. If you’d like to call in a topic request use the Speakpipe widget at the end of the show notes or at pharmacyjoe.com/contact.

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This may be splitting hairs with the definition, but I’d avoid clonidine or any other oral medication in a hypertensive emergency. I’d reserve clonidine for the treatment of acute, asymptomatic hypertension. Clonidine is just a short-term band-aid solution for acute hypertension, as it should not be continued long term. I was unable to find any studies describing a rebound effect from stopping clonidine within the first few days, but there is such an effect seen with dexmedetomidine (another alpha agonist) as early as after 24 hours of treatment, so I suppose it would be possible for your internist to have seen some patients experience a rebound effect after clonidine.

In this episode, I’ll cover treatment strategies for hypertensive emergencies. A hypertensive emergency is present when severe hypertension is associated with acute, ongoing end-organ damage. Severe hypertension in the absence of end-organ damage used to be called a hypertensive urgency, but is now referred to as acute asymptomatic hypertension. Whether treating a hypertensive emergency or acute asymptomatic hypertension, an excessive hypotensive response is potentially dangerous, and may lead to ischemic complications such as stroke, myocardial infarction, or blindness.

End organ damage is typically found in the form of neurologic, cardiac, vascular, or renal damage.

The general goal of treatment for most hypertensive emergencies is to achieve a 10-20% reduction in systolic BP in the first hour, and an additional 5-15% reduction in BP in the first 24 hours.

There are two notable exceptions to this general goal:

1. In the acute phase of ischemic stroke, the blood pressure is usually not lowered unless it is ≥185/110 mmHg in patients who are eligible for alteplase therapy or ≥220/120 mmHg in patients who are not eligible for alteplase therapy.

2. In acute aortic dissection, the systolic blood pressure is rapidly lowered to a target of 100 to 120 mmHg within 20 minutes.

Let’s review each type of hypertensive emergency and the ideal agents to use in each case:

Neurologic emergencies

The most frequent neurologic hypertensive emergencies are ischemic stroke, hemorrhagic stroke, head trauma, and hypertensive encephalopathy.

Ischemic stroke

Use IV labetalol or nicardipine to achieve a BP <185/110 if the patient is eligible for alteplase, or <220/120 if they are not alteplase-eligible.

Hemorrhagic stroke

Treatment of acute hypertenision in the setting of hemorrhagic stroke is a delicate balance between the risk of reducing cerebral perfusion and the benefit of reduced bleeding. IV labetalol or nicardipine are my preferred medications for these patients.

Head trauma

Hypertension is usually treated in this setting only if the cerebral perfusion pressure (mean arterial pressure minus intracranial pressure) is >120 mmHg and the intracranial pressure is >20 mmHg. Use IV mannitol.

Hypertensive encephalopathy

Hypertensive encephalopathy is a diagnosis of exclusion. You won’t know your patient had hypertensive encephalopathy until you lower their blood pressure and see their mental status rapidly improve. If you are suspecting hypertensive encephalopathy I’d use IV nicardipine.

Cardiac emergencies

The most frequent cardiac hypertensive emergencies are acute left ventricular dysfunction with pulmonary edema and acute coronary syndrome.

Acute heart failure

Use IV loop diuretics and nitroglycerine. Avoid hydralazine (increases cardiac work) and beta-blockers (decreases cardiac contractility).

Acute coronary syndrome

Use IV nitroglycerin, nicardipine, or esmolol to reduce the underlying coronary ischemia and/or increased myocardial oxygen consumption and to improve outcomes.

Vascular emergencies

The most frequent vascular hypertensive emergencies include acute aortic dissection and risk to suture lines s/p vascular surgery.

Acute aortic dissection

Remember the goal is to lower the systolic blood pressure rapidly to a target of 100 to 120 mmHg within 20 minutes. Use IV labetalol first and if needed add nitroprusside or clevidipine.

Risk to vascular suture lines after vascular surgery

I am not aware of any studies comparing agents to use in the scenario of hypertensive emergency s/p vascular surgery. I’d use IV nicardipine or labetalol for these patients.

Renal emergencies

Severe hypertension may cause acute hypertensive nephrosclerosis. Antihypertensive therapy often leads to worsening kidney function, sometimes requiring dialysis, although this is sometimes reversible. Fenoldopam, if available, may be a useful antihypertensive in this setting since it is associated with a temporary improvement in renal function.

Other

Other causes of hypertensive emergencies are sympathetic overactivity and pregnancy.

Sympathetic overactivity may be caused by withdrawal of antihypertensives, ingestion of sympathomimetic agents, pheochromocytoma, or autonomic dysfunction. Unless a beta blocker was recently withdrawn, administration of a beta blocker alone is contraindicated in these settings since inhibition of beta receptor-induced vasodilation can result in unopposed alpha-adrenergic vasoconstriction and a further rise in blood pressure.

Withdrawal of short-acting antihypertensive agents

If the patient is in withdrawal from clonidine, oral clonidine will begin to lower the blood pressure within an hour and is the only scenario I’d use an oral antihypertensive in a hypertensive emergency. Oral beta-blockers are too slow to work. If the patient is in withdrawal from a beta-blocker, other IV antihypertensives should be used while the beta-blocker takes effect.

Ingestion of sympathomimetic agents

Examples of ingested sympathomimetic agents are cocaine, amphetamines, and a tyramine/monoamine oxidase inhibitor interaction. IV phentolamine (if available) or nitroprusside can be used.

Pheochromocytoma

Pheochromocytoma can also produce severe hypertension and acute target-organ damage. Use IV nitroprusside, phentolamine, or nicardipine if a hypertensive emergency presents before adrenalectomy can be performed.

Severe autonomic dysfunction

Acute spinal cord injury or Guillain-Barré syndrome is occasionally associated with hypertensive emergency. Use IV phentolamine (if available) or nitroprusside.

Pregnancy

For hypertensive emergencies during pregnancy use IV magnesium sulfate, hydralazine, or labetalol.

A note about clevipidine

Clevidipine is not on formulary at my institution, and I have no experience working with this medication. Looking at the very limited published data on clevidipine, I’d be extremely concerned about over-rapid correction of hypertension with clevidipine, and wouldn’t consider using it for anything I don’t already consider nitroprusside first line for. With the recent price increase of nitroprusside it looks increasingly likely that clevidipine will make its way onto formulary at my institution. If you have experience with clevidipine, I’d love to hear about it. Send me an email or a voicemail over at pharmacyjoe.com/contact.

Useful references for hypertensive emergency

Clinical features in the management of selected hypertensive emergencies

Clinical practices, complications, and mortality in neurological patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension registry

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If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.

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