How fast to lower blood pressure in hypertensive emergency

CONTENTS

• Background
  • Use the MAP
  • Pathophysiology of malignant hypertension
• (1) Is there a known cause of the HTN?
• (2) Is this actually a hypertensive emergency?
• (3) Re-evaluation for an underlying cause of the HTN.
• (4) Control Bp with IV antihypertensive agents.
  • Nicardipine
  • Clevidipine
  • IV Labetalol
  • Nitroglycerine
  • Esmolol
  • (Medications to avoid)
• (5) Transition to oral antihypertensives.
  • Calcium channel blockers
  • PO Labetalol
  • ACEi & ARBs
  • Isosorbide dinitrate & hydralazine
  • Clonidine
• PRES
• Podcast
• Questions & discussion
• Pitfalls

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Preamble: Use the MAP

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Before getting started, it will be useful to define our preferred measurement of blood pressure:  the mean arterial pressure (MAP).   The MAP is the average arterial pressure, which can be estimated as follows:

MAP = [2(diastolic Bp) + Systolic Bp]/3 

There are several reasons that MAP is the preferred measurement of blood pressure, as follows:

reason #1:  MAP is what the automated Bp cuff is actually measuring

• Automated oscillometric Bp cuffs measure the MAP directly (whereas the systolic and diastolic Bp are estimated using proprietary algorithms).
• This could make the MAP the most accurate measurement.

reason #2:  MAP may be most closely related to the risk of hypertensive emergency

• We tend to focus on the systolic blood pressure (“she had a systolic of 250!!”).  However, the risk of hypertensive emergency seems overall be more closely related to the diastolic pressure than the systolic pressure.
• MAP is probably the single parameter most closely related to the risk of hypertensive emergency.

reason #3:  MAP is preferred in guiding therapy 

• The dosing of any antihypertensive drug can be titrated only against a single variable.  The best way to titrate antihypertensive drugs in a logical fashion is to target a specific MAP.
• Trying to titrate an antihypertensive infusion against systolic and diastolic blood pressure simultaneously is often impossible and confusing (for example, what happens if the systolic target is reached but not the diastolic?).

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pathophysiology of malignant hypertension

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what is malignant hypertension?

• When chronic hypertension is not treated, it may eventually reach a tipping point where the hypertension itself is causing progressive microvascular damage.  This leads to a vicious spiral that, if untreated, will progress to death.
• The term “malignant hypertension” is somewhat outdated (classically this was defined based on the presence of extreme hypertension and hypertensive retinopathy – which was often lethal before the advent of antihypertensives).  Nonetheless, as a general concept this remains useful.
  • Malignant hypertension is the “purest” form of primary hypertensive emergency.

pathophysiology of malignant hypertension

• The vicious spiral is shown above.  The core of this spiral is that hypertension causes microcirculatory damage that impairs renal perfusion, leading to activation of the renin-angiotensin system (RAS).  RAS activation, in turn, causes vasoconstriction – which leads to worsening hypertension.
• Clinical implications of this pathophysiology include the following:
  • (#1)  The primary pathophysiological problem is excessive vasoconstriction.  Thus, the optimal treatment may include a vasodilator (most often a calcium channel blocker).  Alternatively, use of a beta-blocker will not address this underlying problem.
  • (#2)  Patients are sometimes intravascularly volume depleted (due to sodium excretion in the kidney that is triggered by the hypertension).  When vasoconstriction is treated, this may unmask underlying volume depletion – which is best treated with IV crystalloid administration.

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(1) Is there a known cause of the HTN?

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secondary hypertension

• Secondary hypertension is used here to refer to hypertension which is a result of some other primary process.  In most cases, the primary process will be more obvious clinically, dominating the initial clinical presentation (e.g. aortic dissection, sympathetic crashing acute pulmonary edema, cocaine intoxication).
• Treatment will vary widely, depending on the specific context.  This will be covered in other chapters regarding these individual conditions.  For example, follow links to:
  • Preeclampsia 📖
  • SCAPE 📖
  • Bp management in ischemic stroke 📖
  • Bp management in intracranial hemorrhage 📖
  • Bp management in subarachnoid hemorrhage 📖
  • Bp management in sympathomimetic intoxication 📖
  • Management of pain 📖
• ⚠️ Please note that the remainder of this chapter doesn't necessarily apply to secondary hypertension.

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(2) Is this actually a hypertensive emergency?

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criteria required to diagnose hypertensive emergency

• (#1) Severe hypertension
  • Usually a MAP of at least >135 mm is needed to cause a hypertensive emergency.(34670853)
  • This may vary considerably depending on the patient's baseline Bp.  The relative change in blood pressure from baseline is more important than it's absolute value.  Hypertensive emergency can occur at lower MAPs in previously normotensive patients who have acute hypertension (e.g., pregnant women with preeclampsia).(26674757)  Alternatively, patients with chronic hypertension may have extremely elevated Bp without hypertensive emergency.
• (#2) Target organ damage, such as:
  • Acute kidney injury (often with microscopic hematuria).
  • Myocardial ischemia (type-II myocardial ischemia).
    • This should be a true myocardial infarction, not solely an elevated troponin.📖
  • Pulmonary edema.
  • Hypertensive encephalopathy (e.g., visual disturbance, seizure, delirium).  In situations where this is unclear, the presence of increased optic nerve sheath diameter on ultrasonography might support the diagnosis of hypertensive encephalopathy with increased intracranial pressure.
  • Note:  Epistaxis, proteinuria, chronic renal failure, or headache don't qualify as target organ damage.(34670853)

“hypertensive urgency” (asymptomatic uncontrolled hypertension)

• “Hypertensive urgency” is a term that has been used to refer to patients with severely elevated blood pressure (e.g., >~180/120) who do not have target organ damage.  However, this is a misnomer because there is no “urgent” need to reduce the blood pressure, specifically:
  • (1) There is NO need for referral to the emergency department.
  • (2) There is NO need for hospital admission.
  • (3) There is definitely NO need for ICU admission!
  • If there is any doubt about this, please see the the AHA/ACC guidelines reproduced below.(29133354)  Aggressive reduction in blood pressure is more likely to cause harm than benefit in this clinical context.  
• It would probably be ideal to eliminate the term “hypertensive urgency” and replace it with the term “asymptomatic uncontrolled hypertension” (which might discourage over-reacting to this condition).(34670853)
• If a patient with hypertensive urgency is encountered in the outpatient context, it might be reasonable to start them on a low dose of a chronic oral antihypertensive agent with a relatively benign side-effect profile (e.g., amlodipine).  It might also be reasonable to arrange close follow-up with their primary care provider for management of their blood pressure.  Obtaining adequate follow-up and ambulatory blood pressure measurement is probably more important than the immediate patient management.  This is not a critical care topic, so it's beyond the scope of this book.

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(3) Re-evaluate for any underlying disease process causing HTN

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causes of severe hypertension 

• Nonadherence with antihypertensive medications (especially clonidine withdrawal).
• Nonadherence with CPAP or BiPAP therapy for sleep disordered breathing.
• Volume overload.
• Pain, anxiety, urinary obstruction.
• Sympathomimetic drugs (e.g., cocaine, over-the-counter decongestants).
• Other medications (e.g., cyclosporine, tacrolimus, erythropoietin, steroid, NSAIDs, anti-angiogenic drugs).
• Withdrawal (e.g., from alcohol or benzodiazepines).
• Stroke (e.g., ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage).
• Sympathetic crashing acute pulmonary edema (SCAPE).
• Aortic dissection.
• Preeclampsia.
• Endocrinopathy (e.g., pheochromocytoma, hyperaldosteronism, Cushing's syndrome, hyperthyroidism).
• Renal (scleroderma renal crisis, acute glomerulonephritis, renal artery stenosis).

evaluation may include:

• Repeat blood pressure measurement:  Initial Bp measurement in the emergency department is often transiently elevated (possibly reflective of a “white coat hypertension” phenomenon).  Simply allowing the patient to rest quietly and repeating the blood pressure will often lead to a substantial reduction.(34670853)
• History: (31279421)
  • Baseline Bp (if known)?
  • History of hypertension? (if so:  Antihypertensive regimen?  Compliance with regimen?)
  • Any prior episodes of hypertensive emergency?
  • Symptoms (including chest discomfort, dyspnea, weakness, visual disturbance, headache)?
  • Illicit drug use?
• Bedside ultrasonography:
  • Volume status?
  • Evidence of aortic dissection?
  • Evidence of left ventricular hypertrophy?
  • Pulmonary edema on lung ultrasonography?
• Labs:
  • Basic labs (chemistries, CBC, coagulation studies).
  • Troponin (only if EKG/clinical evidence to support MI).
  • Urinalysis.
  • Urine toxicology screen may be considered.
  • Pregnancy evaluation as appropriate.
• EKG.
• Non-contrast head CT, if presentation is worrisome for possible intracranial hemorrhage.

diagnostic/therapeutic management of any obvious causes of hypertension

• Blood pressure can be affected by a myriad of factors.  Before initiation of antihypertensives, consider some simple interventions which may be highly effective in reducing the blood pressure (e.g., analgesia).  Overlooking these factors may eventually lead to overshoot hypotension.  For example, if pain is driving the hypertension but you initiate therapy with antihypertensives first, when the pain eventually resolves the patient may develop overshoot hypotension.  
• Interventions which may rapidly reduce the blood pressure:
  • Pain:  Treat with appropriate analgesia.
  • Agitation:  Treat with antipsychotics or dexmedetomidine.
  • Volume overload:  Treat with diuresis or dialysis.
  • Alcohol withdrawal:  Phenobarbital.
  • Urinary retention:  Foley catheter.

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(4) Control Bp with IV antihypertensives

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blood pressure goal?

• There isn't solid evidence behind this.  The following approach seems reasonable & consistent with guidelines: (29133354, 30165588)
  • (#1) The initial goal is to decrease the MAP by ~20% within 1-2 hours.
  • (#2) If this reduction is tolerated, then decrease the MAP to ~125 mm (~160/110 mm) over the next 2-6 hours.
  • (#3) The blood pressure may subsequently be gradually decreased further over a period of days, as clinically tolerated.
• These general recommendations may not hold for every patient.  Consider what the patient's baseline pressure is, and how rapid the increase in pressure was.
  • For a patient with chronic hypertension, a more gradual approach to lowering the Bp may be wise.
  • For a patient with very acute development of hypertension (e.g. postoperatively or due to an acute ingestion), more rapid reduction of Bp may be reasonable.
• 💡 Whenever possible, try to clearly define the baseline Bp (e.g., obtain multiple Bp readings in both arms before starting antihypertensives).  Lack of a definite baseline Bp leads to uncertainty regarding all downstream Bp targets.

understanding hypertensive infusions:  titratable vs. quasi-titratable vs. bolus

• In general:
  • Continuous infusions are used for drugs with a short half-life (e.g. norepinephrine).  The short half-life means that the drug needs to be infused continuously.  It also makes the drug easily titratable.
  • Intermittent boluses are used for drugs with longer half-lives (most drugs).
• Anti-hypertensive drugs can be classified into roughly three groups:
• (1) Truly titratable agents
  • Duration of action is <<30 minutes.
  • The drug must be given as a continuous infusion.  It is fairly easy to titrate.
  • Examples:  Nitroglycerine, esmolol, clevidipine.
• (2) Quasi-titratable agents
  • Duration of action is <1-2 hours.
  • The drug is generally given as a continuous infusion, but it's a bit sluggish to titrate.
  • Examples:  Nicardipine, diltiazem.
• (3) Bolus agents
  • Duration of action is >1-2 hours
  • The easiest way to give the drug is as intermittent bolus doses.  If an infusion is used, it will tend to accumulate and be rather difficult to titrate.
  • Examples:  Labetalol, metoprolol.

is an arterial line needed?

• There is no good data on this.
• Indications for an arterial line might include:
  • Very labile blood pressures.
  • Profound hypertension (too high to be real?).
  • Clinical deterioration despite noninvasive management.
• An arterial line is probably unnecessary in most cases of hypertensive emergency, for the following reasons.
  • (1) The pain of arterial line insertion can exacerbate hypertension.
  • (2) No prospective evidence exists to show that this procedure is beneficial or necessary.
  • (3) Bp targets are arbitrary and poorly defined.  It's illogical to tightly chase after an arbitrary target.

if the blood pressure plummets, evaluate for hypovolemia and volume resuscitate if necessary 

• Patients often have a combination of:
  • (1) Excessive vasoconstriction, which is driving their hypertension.
  • (2) Hypovolemia due to the diuretic effect of hypertension (“pressure diuresis”).
• When treated with vasodilation, these patients may develop hypotension (due to unmasking of their hypovolemia).  Overall this may lead to wide fluctuations in blood pressure, which is difficult to control.  Stabilizing these patients requires addressing both problems:
  • (1) Control excessive vasoconstriction with a vasodilator.
  • (2) Control hypovolemia with volume administration.

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nicardipine

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advantages & general comments 💊

• Good for most situations (often the workhorse agent in hospitals that don't have clevidipine).
• Seems more powerful than most other agents (e.g., labetalol).

drawbacks & contraindications

• Contraindications
  • Cirrhosis (cleared by the liver).
• Drawbacks
  • Longish half-life may give the infusion a tendency to accumulate and cause hypotension.  This may be avoided by cutting the infusion back once the target blood pressure is reached (see “dose” section below).
  • May promote volume overload (nicardipine is often provided in a relatively dilute form that may cause substantial volume administration).
  • May cause headache, reflex tachycardia.

onset & duration

• Onset ~5-15 minutes.
• Lasts ~1 hour.

dose

• Start at 5 mg/hr.
• If Bp is above target, increase by 2.5 mg/hr every 15-30 min, to a maximum rate of 15 mg/hour.
• When Bp reaches target, reduce the infusion to 3-5 mg/hr to prevent accumulation.
• If Bp falls below target, decrease infusion to 2.5 mg/hr or stop entirely.
• If the blood pressure falls substantially below target, stop the infusion entirely.

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clevidipine

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advantages & general comments 💊

• Similar to nicardipine, but it has a shorter half-life which allows it to be a truly titratable agent.
  • Clevidipine has been shown to be more successful than nicardipine at achieving tight blood pressure control.(18806012)  It's easier to use than nicardipine, with a lower risk of overshoot hypotension.
• Clevidipine is provided in a milky lipid emulsion (similar to propofol).

drawbacks & contraindications

• Contraindications
  • Hyperlipidemia, lipoid nephrosis, or acute pancreatitis.
  • Technically contraindicated in patients with hypersensitivity to egg/soy.
• Drawbacks
  • Unavailable at many hospitals due to cost/acquisition barriers.
  • May cause reflex tachycardia, headache.

onset & duration

• Onset in 2 minutes.
• Lasts 10 minutes.

dose

• Start at 1-2 mg/hour
• Double every 2 minutes until Bp begins approaching target, then titrate by smaller increments every 5-10 minutes.
• Dose range is 1-32 mg/hour (use low-end dose range in elderly patients)

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IV labetalol

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advantages & general comments 💊

• Labetalol is a reasonable agent in most situations, especially if you're trying to drop the Bp by only a moderate amount (e.g., 10-30 mm).  For profound hypertension, labetalol seems less effective than nicardipine.
• Labetalol may be preferred to nicardipine if concurrent MI.
• The problem with labetalol for hypertensive emergency is that labetalol often doesn't address the underlying physiological problem.  The primary driver of most hypertensive emergencies is excessive afterload (vasoconstriction).  However, labetalol works predominantly as a beta-blocker (with negative inotropic and negative chronotropic effects).  Beta-blocking someone with excessive afterload could theoretically reduce the cardiac output and thereby promote systemic hypoperfusion.  This may explain why labetalol is less effective than medications which cause vasodilation (e.g., nicardipine).

drawbacks & contraindications

• Contraindications:
  • Bradycardia.
  • Heart block or sick sinus syndrome.
  • Cardiogenic pulmonary edema.
  • Asthma exacerbation.
  • Acute cocaine/sympathomimetic intoxication.
• Drawbacks
  • Can cause bradycardia.
  • Nonselective beta-blocker, so it may cause hyperkalemia.
  • High doses may cause fetal bradycardia (>800 mg per day)(30165588)

onset & duration

• Onset in 5-10 minutes.(30165588)
• Lasts 3-6 hours.(30165588)

dose

• (#1)  Start with sequential pushes of 20mg, 40mg, 80mg, 80mg, 80mg (q15 min PRN).
  • Escalating boluses of labetalol can be useful to achieve rapid control of severe hypertension at the bedside if this is needed (e.g. acute Bp spike which requires immediate control).
  • If a total dose of 300mg doesn’t work, switch to another agent.
  • Individual responses vary.
• (#2)  Once Bp controlled, may use intermittent boluses to keep the blood pressure in range (e.g. 10-20 mg IV q10 minutes PRN).
  • The optimal bolus dose will vary between patients.  This may be determined empirically as described above in #1.  The goal of the bolus dose is to drop the Bp effectively, but not excessively.
  • The blood pressure must be monitored carefully, with repeat PRN doses used as necessary (figure below).
• Labetalol lasts ~2-4 hours, so it doesn't make sense to give it as a continuous infusion (a continuous infusion will gradually accumulate and eventually cause overshoot hypotension).

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nitroglycerine

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advantages & general comments 💊

• Agent of choice for acute cardiogenic pulmonary edema (SCAPE).
• Coronary vasodilation may be helpful in myocardial ischemia.
• Short half-life allows this to be a truly titratable agent (which can be rapidly up- and down-titrated to achieve a blood pressure target).

drawbacks & contraindications

• Contraindications
  • Phosphodiesterase inhibitors use (e.g. sildenafil) within 48 hours.
  • Elevated ICP (intracranial pressure).
  • Reported to worsen PRES (posterior reversible encephalopathy syndrome).
• Drawbacks
  • May cause headache, reflex tachycardia.
  • Ongoing use may eventually lead to tachyphylaxis.

onset & duration

• Onset within 2 minutes.
• Lasts ~5-10 minutes.

dose

• 0-800 mcg/min (although no exact maximal dose is known).  Most patients with hypertensive emergency can be managed with doses in the ~50-300 mcg/min range.  Note that doses required for control of hypertension are much higher than doses utilized for management of angina.
  • Lower doses cause venodilation, whereas higher doses are needed to achieve arterial vasodilation.

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esmolol

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advantages & general comments 💊

• Very short-acting beta blocker, allowing it to be used as a titratable agent.
• Esmolol is a pure beta-blocker (unlike labetalol, which is an alpha-beta blocker).  Since it only blocks beta receptors, esmolol is a less powerful agent than labetalol.

drawbacks & contraindications

• Contraindications
  • Bradycardia.
  • Heart block or sick sinus syndrome.
  • Cardiogenic pulmonary edema.
  • Asthma exacerbation.
  • Acute cocaine/sympathomimetic intoxication.
• Drawbacks
  • May not be effective in patients with profound hypertension.

onset & duration

• Onset in 1-2 minutes.(30165588) 
• Lasts 10-30 minutes.(30165588)

dose

• Loading dose = 0.5 mg/kg.
• Start infusion at 50 mcg/kg/min.
• For persistent hypertension, re-load (with 0.5 mg/kg) and increase infusion by 50 mcg/kg/min. Up-titrate as needed to a max dose of 200 mcg/kg/min.

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medications to avoid

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nitroprusside

• Reasons not to use nitroprusside:
  • (1) Can increase the intracranial pressure.
  • (2) Can cause cyanide toxicity and lactic acidosis – which may create a confusing picture if the patient deteriorates.
  • (3) Tends to cause wide swings in the blood pressure (requires continuous close attention and meticulous titration).  If nitroprusside is used, an arterial line should probably be inserted to allow for adequate monitoring of these blood pressure swings.
  • (4) Coronary vasodilation can cause a steal phenomenon that promotes myocardial ischemia.
• Generally, another agent will be equally effective and safer.
• Given lack of any high-quality evidence that tight Bp control improves outcomes, it's challenging to justify the risks involved with using nitroprusside.

intravenous hydralazine

• Reasons not to use IV hydralazine
  • (1) Effect is unpredictable (sometimes minimally effective, sometimes causes precipitous Bp drop)
  • (2) Impossible to titrate (works for 2-4 hours)
• Most situations, another agent will be equally effective and safer (one potential exception is preeclampsia with refractory hypertension).

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(5) Transition to oral antihypertensives

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when to start oral titration

• Start oral antihypertensives after the patient has stabilized and improved on IV antihypertensives for several hours.
• Oral antihypertensives may be gradually up-titrated, with simultaneous weaning off IV antihypertensives.

preamble on oral antihypertensives & dose-stacking

• The key concern with oral antihypertensive agents is how rapidly they take effect.  As in any other situation where you're up-titrating medications (e.g. procedural sedation), it's important to allow one dose of medication to take effect before you escalate the dose.
  • If doses are escalated before the last dose has taken effect, this may eventually lead to an excessive drop in blood pressure.
• The ideal oral antihypertensive will take effect in under ~2 hours.  This allows for a fairly prompt up-titration of oral doses, which allows rapid weaning of the IV antihypertensive agent.

agents to avoid

• Amlodipine takes forever to work – this drug is an absolute slug and has no role here.
• Metoprolol drops heart rate, but is relatively ineffective for controlling blood pressure.
• Carvedilol is an alpha/beta blocker, similar to labetalol.  It's a reasonable choice, but with a half-life of 6-10 hours it takes a few doses to reach steady state.  This precludes the ability to perform rapid oral dose-titration.  If the dose of carvedilol is rapidly escalated (e.g., every 12 hours), then doses will have a tendency to stack – and eventually this may lead to hypotension.

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calcium channel blockers

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advantages & general comments

• These are essentially oral analogues of IV nicardipine or IV clevidipine.  Similar to nicardipine or clevidipine, they are widely applicable and generally effective.  Nifedipine XR and isradipine are favored here, due to their reasonably fast onset (unlike amlodipine, which takes days to work).
• Nifedipine extended release 💊  is generally an excellent choice.  This can be used as a once-daily medication, facilitating transition to the ward and outpatient therapy.
  • (⚠️ Immediate release nifedipine can cause rapid drops in the pressure and shouldn't be used.)
• Isradipine 💊  is very fast-acting, but it has the drawback of being a bit more expensive and less widely available.

drawbacks & contraindications

• Nifedipine XR cannot be crushed and administered via feeding tube.

onset & duration

• Nifedipine XR:
  • Onset within ~2-4 hours.
  • Duration of action ~24 hours.
• Isradipine:
  • Onset within ~2 hours.
  • Duration of action ~10 hours.

dose

• Nifedipine XR:
  • Starting dose is 30-60 mg.
  • Max dose may vary depending on formulation (90 mg daily for Adelat CC, or 120 mg daily Procardia XL).
• Isradipine:
  • Start 2.5 mg q12.
  • Max dose 5 mg q12.

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PO labetalol

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advantages & general comments 💊

• Labetalol is traditionally a preferred oral antihypertensive for hypertensive emergency.
• As an alpha-beta blocker, labetalol is more effective at lowering blood pressure than pure beta-blockers (e.g., metoprolol).
• For patients who respond well to IV labetalol, a transition to oral labetalol makes sense.  PRN doses of IV labetalol can be continued after starting oral labetalol for management of breakthrough hypertension.  Meanwhile, the dose of oral labetalol may be gradually increased until no additional PRN IV doses are needed.

drawbacks & contraindications

• Contraindications
  • Bradycardia
  • Heart block or sick sinus syndrome
  • Cardiogenic pulmonary edema
  • Asthma exacerbation
  • Cocaine/sympathomimetic toxicity

onset & duration

• Onset in ~2 hours.
• Duration of ~10 hours.

dose

• Start 200 mg q12hr.  If no effect is seen following the first dose, an additional dose may be considered after 2-4 hours, followed by a subsequent increase in the maintenance dose.
• Max dose 1,000 mg q12hr.

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ACEi & ARB

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advantages & general comments 

• Generally not utilized, for the following reasons:
  • Risk of renal failure.
  • Effects may be widely variable between patients, depending on the patient's level of endogenous activation of their renin/angiotensin/aldosterone system.
• Situations where ACEi/ARB may be useful:
  • (1) Patients with systolic heart failure.
  • (2) Patients previously on ACEi/ARB.
  • (3) Patients with SCAPE, who are at risk of recurrent episodes of SCAPE.
  • (4) Patients with renal failure on dialysis.
  • (5) Front line therapy for patients with scleroderma renal crisis.
• The optimal agent is probably oral captopril, because it has a fast onset and short duration of action (which allows for facile oral titration).  Small captopril doses can be initiated cautiously and up-titrated as tolerated.  Once the patient has been stabilized on captopril, this may eventually be transitioned to an equivalent dose of lisinopril using a 5:1 conversion (the total daily dose of captopril divided by five will approximate an equivalent lisinopril dose).(8773158) 🌊  Lisinopril is preferred for chronic therapy, since it can be given once daily.

drawbacks & contraindications

• Contraindications:
  • Hyperkalemia.
  • Renal failure (but not chronic ESRD on hemodialysis).
  • Prior intolerance or cough (especially with ACE inhibitors).
• Drawbacks:
  • Can promote renal failure, should be avoided if there is acute kidney injury or other nephrotoxic medications.

onset & duration

• Captopril:
  • Onset in 15-30 minutes.
  • Duration ~6 hours.
• Losartan or Telmisartan:
  • Onset in ~4-6 hours (Telmisartan has faster onset; losartan is slower if administered with food).
  • Duration ~24 hours.

dose 🌊

• Captopril 💊
  • Start 12.5 mg q8hr.
  • Max dose 50 mg q8hr.
• Losartan 💊
  • Start 50 mg daily.
  • Max dose 100 mg daily.
• Telmisartan 💊
  • Start 40 mg daily.
  • Max dose 80 mg daily.

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isosorbide dinitrate & hydralazine

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advantages & general comments

• May be useful in patients with heart failure (the overall physiological effect is similar to an ACE inhibitor, but without a risk of nephrotoxicity).
• Short duration of action may facilitate rapid oral titration.

drawbacks & contraindications

• Contraindications
  • Hydralazine is contraindicated in patients with hypertrophic obstructive cardiomyopathy, or left ventricular outflow tract obstruction.
• Drawbacks
  • Hydralazine may cause reflex tachycardia.
  • Renal dysfunction may cause hydralazine to accumulate over time.

onset & duration

• Hydralazine 💊
  • Onset within ~1 hour.
  • Duration of ~8 hours.
• Isosorbide dinitrate 💊
  • Onset within ~1-2 hours.
  • Duration of ~8 hours.

dose

• Hydralazine
  • Start 25-37.5 mg q8hr.
  • Max dose 100 mg q8hr.
• Isosorbide dinitrate
  • Start 20 mg q8hr.
  • Max dose 40 mg q8hr.
• 💡 Doses may be staggered every four hours (i.e., alternating doses of hydralazine and isosorbide dinitrate every four hours) to avoid causing an excessive drop in blood pressure.

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clonidine

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advantages & general comments 💊

• An advantage of clonidine is that it works very rapidly – which may allow for prompt oral dose-titration.
• Especially useful in:
  • Anxiety.
  • Opioid withdrawal.
  • Patients previously on clonidine.

drawbacks & contraindications

• Contraindications
  • Depressed mental status (clonidine may cause somnolence).
• Drawbacks
  • Not good medication for chronic use (risk of rebound hypertension).

onset & duration

• Onset ~ 1 hour.
• Duration ~12 hours.

dose

• Start at 0.2 mg q12hr.
• Max dose 1.2 mg q12hr.

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podcast

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• #1 most common mistake = overdiagnosis of hypertensive emergency among patients with scary high Bp but no target organ damage.  This isn't a hypertensive emergency, please don't call the ICU for this.  Thanks in advance.
• #2 most common mistake = treating hypertensive emergency too aggressively and dropping the Bp too much and too fast.
• #3 most common mistake = trying to transition from an antihypertensive infusion to an oral agent that takes a long time to have any effect on blood pressure (e.g. amlodipine).  This causes patients to be stuck in the ICU on an infusion forever.  It's also unpredictable when these drugs take effect, so there is a risk of dose-stacking (i.e. you keep up-titrating oral agents and eventually they all kick in simultaneously, causing hypotension).
• Generally avoid IV hydralazine; this has erratic effects and sometimes bottoms out the blood pressure.
• Don't use IV metoprolol for blood pressure control.  Metoprolol isn't very effective for control of blood pressure, but it will slow down the heart rate.  That actually makes matters worse, because then you can't use labetalol (since the patient is already bradycardic).

Guide to emoji hyperlinks 

Going further 

• EMCrit 190:  Emergencies with a side of hypertension
• Hypertensive emergencies (Emergency Medicine Cases, Anton Helman)
• Hypertensive Emergency (WikEM)

References

• 18806012  Aronson S, Dyke CM, Stierer KA, Levy JH, Cheung AT, Lumb PD, Kereiakes DJ, Newman MF. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg. 2008 Oct;107(4):1110-21. doi: 10.1213/ane.0b013e31818240db  [PubMed]
• 26674757  Leiba A, Cohen-Arazi O, Mendel L, Holtzman EJ, Grossman E. Incidence, aetiology and mortality secondary to hypertensive emergencies in a large-scale referral centre in Israel (1991-2010). J Hum Hypertens. 2016 Aug;30(8):498-502. doi: 10.1038/jhh.2015.115  [PubMed]
• 29133354  Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):1269-1324. doi: 10.1161/HYP.0000000000000066  [PubMed]
• 30165588  van den Born BH, Lip GYH, Brguljan-Hitij J, Cremer A, Segura J, Morales E, Mahfoud F, Amraoui F, Persu A, Kahan T, Agabiti Rosei E, de Simone G, Gosse P, Williams B. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur Heart J Cardiovasc Pharmacother. 2019 Jan 1;5(1):37-46. doi: 10.1093/ehjcvp/pvy032  [PubMed]
• 31279421  Brathwaite L, Reif M. Hypertensive Emergencies: A Review of Common Presentations and Treatment Options. Cardiol Clin. 2019 Aug;37(3):275-286. doi: 10.1016/j.ccl.2019.04.003  [PubMed]
• 34670853  Jolly H, Freel EM, Isles C. Management of hypertensive emergencies and urgencies: narrative review. Postgrad Med J. 2021 Oct 20. doi: 10.1136/postgradmedj-2021-140899  [PubMed]