Approach

If hypertensive emergency is suspected, treatment should not be delayed while conducting a full diagnostic evaluation.

Appropriate facilities

Patients with hypertensive emergencies should be admitted to an intensive care unit for continuous monitoring of blood pressure (BP) and target organ damage and for parenteral administration of appropriate therapeutic agent(s).[1][7]​​[18][74] Other supportive measures that may be required include intracranial pressure monitoring (in rare cases of increased intracranial pressure), noninvasive ventilation or intubation (in cases of respiratory distress), or dialysis (in case of severe acute kidney injury).

Choice of agents and route of administration

The specific parenteral agents used for treating a hypertensive emergency should be dictated by the end-organ systems that have been damaged, patient comorbidities, and overall clinical condition. Oral therapies are generally discouraged as first-line treatment options.[1] Arterial lines are preferred for the use of intravenous antihypertensive medications.[7]​ There are very few randomized controlled trials studying different parenteral agents in hypertensive emergency. Published guidelines are therefore based on common clinical experience and practice.

Rate of BP reduction

The American College of Cardiology/American Heart Association Task Force on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure states that the initial goal of therapy in hypertensive emergencies is to reduce mean arterial BP by no more than 25% (within minutes to 1 hour), then, if stable, to 160 mmHg systolic and 100-110 mmHg diastolic within the next 2-6 hours.[1]

Excessive falls in pressure that may precipitate renal, cerebral, or coronary ischemia should be avoided.[1][57]

If the initial level of reduced BP is well tolerated and the patient is clinically stable, further gradual reductions toward a normal BP can be implemented over the next 24-48 hours.

Exceptions to the above recommendation include:[1][75]

  • Patients with an ischemic stroke, as there is no clear evidence from clinical trials to support the use of immediate antihypertensive treatment

  • Patients who are candidates for thrombolytic therapy (typically those with ischemic stroke), who should have their BP slowly lowered to systolic BP (SBP) <185 mmHg and diastolic BP <110 mmHg before intravenous tissue plasminogen activator is initiated

  • Patients with severe preeclampsia, eclampsia, or pheochromocytoma crisis, in whom SBP should be reduced to <140 mmHg in the first hour

  • Patients with aortic dissection, in whom accepted practice is reduction of SBP to <120 mmHg in the first 20 minutes, although evidence to support this timescale is lacking.

Accelerated (malignant) hypertension, hypertensive encephalopathy or intracranial hemorrhage

The term "accelerated hypertension" (also known as malignant hypertension) is a subcategory of hypertensive emergency where severe hypertension occurs with retinopathy of grade III (flame hemorrhages, dot and blot hemorrhages, hard and soft exudates) or grade IV (papilledema).[18][54]

Hypertensive encephalopathy encompasses the transient neurologic symptoms (lethargy, seizures, cortical blindness, and coma) that occur with malignant hypertension, which are usually reversed by prompt treatment and lowering of BP.[18][54]​ Encephalopathy should improve once the BP is lowered. If there is no improvement despite a decrease in BP, an alternative diagnosis should be considered.

In the management of intracerebral hemorrhage (ICH), the patient's ideal BP should be based on individual factors, including baseline BP, presumed cause of hemorrhage, age, elevated intracranial pressure, and interval since onset. In cases of large or severe ICH, or an initial SBP ≥220 mmHg, cautious BP lowering should be pursued.[76] In patients with initial SBP ≥220 mmHg, early intensive BP reduction, compared with standard BP lowering, was associated with higher rates of renal adverse events in one post-hoc analysis of a large randomized clinical trial.​​[76][77]​​​

While elevated BP could in theory increase the risk of ongoing bleeding from ruptured small arteries and arterioles, the relationship between BP, intracranial pressure, and volume of hemorrhage is complex and not yet fully understood.

The rationale for lowering BP is to minimize further hemorrhage: for example, from a ruptured aneurysm or arteriovenous malformation. However, the evidence for the effectiveness and safety of rapid BP lowering in the management of intracerebral hemorrhage remains inconclusive.[76][78]​​[79][80]​​​​

For the management of patients with spontaneous ICH, recommendations from the American Heart Association and American Stroke Association (AHA/ASA) include the following, based on two of the largest trials for early intensive BP lowering after ICH (INTERACT2, ATACH-2), meta-analyses, and several post-hoc analyses of these two trials:[76][78][79]

  • In patients with spontaneous ICH requiring acute BP lowering, careful titration to ensure continuous smooth and sustained control of BP, avoiding peaks and large variability in SBP, can be beneficial for improving functional outcomes.

  • Initiating blood pressure treatment within 2 hours of ICH onset, and reaching target within 1 hour, can be beneficial to reduce the risk of hematoma expansion and improve functional outcomes.

  • In patients with spontaneous ICH of mild to moderate severity presenting with SBP between 150 and 220 mmHg, acute lowering of SBP to a target of 140 mmHg, with the goal of maintaining it within the range of 130-150 mmHg, is safe and may be reasonable for improving functional outcomes. Acute lowering of SBP to <130 mmHg is potentially harmful in these patients.

  • In patients with spontaneous ICH presenting with large or severe ICH, SBP >220 mmHg, more than 6 hours after symptom onset, or in those requiring surgical decompression, the safety and efficacy of intensive BP lowering is not well established.

See Hemorrhagic stroke (Management approach).

Treatment options include the following.

  • First-line

    • Labetalol is the first-line treatment for accelerated (malignant) hypertension, hypertensive encephalopathy, or intracranial hemorrhage.[18][39][41][42]

  • Second-line

    • Nicardipine is a second-line agent.[18]​ One randomized controlled trial found that intravenous nicardipine significantly increased the proportion of people who reached physician-specified target range SBP within 30 minutes compared with intravenous labetalol.[81] Nicardipine is especially useful in the presence of cardiac disease due to coronary vasodilatory effects.[82][83]

    • If patients do not have evidence of raised intracranial pressure, nitroprusside is a second-line treatment choice.[39][41] However, if raised intracranial pressure is present or suspected, nitroprusside is contraindicated and another agent should be used.[18][84]​ Nitroprusside decreases cerebral blood flow while increasing intracranial pressure, effects that are particularly disadvantageous in patients with hypertensive encephalopathy or following a stroke.[85][86][87] It should also be avoided in patients with renal or hepatic insufficiency.

  • Third-line

    • The third-line treatment choice is fenoldopam, a selective peripheral dopamine-1-receptor agonist with arterial vasodilator effects.[39][41][42][88][89] This drug is particularly useful in patients with renal insufficiency, where the use of nitroprusside is restricted due to the risk of thiocyanate poisoning.

Acute ischemic stroke

Treating a hypertensive emergency with an associated acute ischemic stroke warrants greater caution in reducing BP than in other types of hypertensive emergency. Overly rapid or large reductions of mean arterial pressure may decrease cerebral perfusion pressure to a level that could theoretically worsen brain injury. However, AHA/ASA guidelines recommend early treatment of hypertension when required by comorbid conditions, including preeclampsia/eclampsia.[69]​ The following may be used as guidance.

If the SBP is >220 mmHg or the diastolic BP is >120 mmHg, it may be reasonable to lower the BP by 15% during the first 24 hours after the onset of stroke.[1][90]

If the SBP is <220 mmHg and the diastolic BP is <120 mmHg, then it is reasonable to maintain close observation without direct intervention to reduce BP, unless:[1][91][92]

  • There is other end-organ involvement such as aortic dissection, renal failure, or acute myocardial infarction

  • The patient is to receive thrombolysis, in which case the target SBP should be <185 mmHg and diastolic BP <110 mmHg. The BP should be maintained <185/105 mmHg for at least 24 hours after initiating intravenous thrombolysis.

If the SBP is >220 mmHg or diastolic BP is between 121-140 mmHg, then labetalol, nicardipine, or clevidipine should be used to achieve a 10% to 15% reduction in BP in 24 hours.[39][41][42][93][94]

If diastolic BP is >140 mmHg, then nitroprusside is used to achieve a 10% to 15% reduction over 24 hours.[39][41][95]

Myocardial ischemia/infarction

First-line treatment of hypertensive emergency complicated by myocardial ischemia or infarction is the combination of esmolol (a selective beta-blocker) plus nitroglycerin (a peripheral vasodilator, which affects venous vessels more than arterial).[1][39][41][42][95][96]

Esmolol acts to reduce the heart rate and nitroglycerin acts to decrease preload and cardiac output, and increases coronary blood flow.

Second-line treatment choice would be labetalol plus nitroglycerin.[39][41][42][95][96]

Contraindications to beta-blockers include moderate-to-severe left ventricular failure with pulmonary edema, bradycardia, hypotension, poor peripheral perfusion, second- or third-degree heart block, and reactive airway disease.[1]

The third-line treatment choice would be nitroprusside.[39][41][95]

Left ventricular failure and/or pulmonary edema

First-line treatment of hypertensive emergency with left ventricular failure and/or pulmonary edema is nitroglycerin or clevidipine.[39][41][42][96]

Nitroprusside (a potent arterial and venous vasodilator that decreases after-load and preload) is the second-line treatment choice in this situation.[39][41][95]

If the patient is not already on a loop diuretic, one should be started (e.g., furosemide). Beta-blockers are contraindicated in moderate-to-severe left ventricular failure with pulmonary edema.[1]

Suspected aortic dissection

If aortic dissection is suspected in a hypertensive emergency, the BP should be lowered quite aggressively, typically with a target of reducing the SBP to <120 mmHg within 20 minutes, although evidence to support this timescale is lacking.[1][75]

Medical therapy aims to both lower the BP and decrease the velocity of left ventricular contraction, so decreasing aortic shear stress and minimizing the tendency for propagation of the dissection.

First-line treatment choice is beta-blockers, either labetalol or esmolol, administered intravenously.[39][41][42][97]

If there is no significant improvement, nitroprusside or nicardipine can be added to the beta-blocker.[39][41][42][97]​ The beta-blockade should precede vasodilator (nicardipine or nitroprusside) administration to prevent reflex tachycardia and worsen shear stress on the intimal flap.[1]​ See Aortic dissection.

Acute kidney injury

Fenoldopam is the first-line treatment choice of hypertensive emergency complicated by acute kidney injury.[39][41][42][88][89]​ This drug (a selective peripheral dopamine-1-receptor agonist with arterial vasodilator effects) is particularly useful in renal insufficiency because it acts to both decrease afterload and increase renal perfusion. Other potential first-line agents are dihydropyridine calcium-channel blockers (e.g., nicardipine, clevidipine), which increase stroke volume and have strong cerebral and coronary vasodilatory activity.[1][39][41][42][93]

Hyperadrenergic states

Hyperadrenergic states include:

  • Pheochromocytoma

  • Sympathomimetic drug use: for example, cocaine, amphetamines, phenylpropanolamine, phencyclidine, or the combination of monoamine oxidase inhibitors with foods rich in tyramine

  • Following abrupt discontinuation of a short-acting sympathetic blocker.

If the hyperadrenergic state is due to sympathomimetic drug use, the first-line agents are benzodiazepines, and antihypertensive medications are given only if the BP response is inadequate.[18][54]​ Benzodiazepines reduce agitation and prevent neurologic complications such as seizures by their action on gamma-aminobutyric acid receptors.[18]​ In all other clinical situations, the first-line treatment choice is phentolamine (which acts by blocking alpha-adrenoceptors) or calcium-channel blockers (clevidipine and nicardipine).[1][39][41][42]​ A beta-blocker (such as labetalol) can be added after sufficient alpha-adrenoceptor blockade. The administration of a beta-blocker alone is contraindicated, since inhibition of beta-adrenoceptor-induced vasodilation results in unopposed alpha-adrenergic vasoconstriction and a further rise in BP.[54]

Severe hypertension in pregnancy (preeclampsia and eclampsia)

For acute-onset, severe hypertension managed in a critical care setting, intravenous labetalol, intravenous hydralazine, or oral nifedipine can be used first line. Labetalol is usually considered the antihypertensive of choice, and is effective as monotherapy in 80% of pregnant women.[48][61]​​​​​​​​[98][99]​​​​​​ It seems to be safe and effective in pregnant women for the management of preeclampsia; however, it should be avoided in women with asthma or any other contraindication to its use.[48]​​ Immediate-release oral nifedipine may also be considered first-line therapy, particularly when intravenous access is not available.[48] Although intravenous hydralazine is still widely used, particularly in North America, it can produce an acute fall in BP.[63]​ The consequences of this are mostly related to maternal hypotension, including a greater risk of cesarean section, more frequent placental abruption, more maternal oliguria, and fetal tachycardia, suggesting the need for close monitoring of maternal BP and fetal wellbeing during its use.[63]​ The UK guidelines recommend to consider volume expansion with crystalloid fluid before or at the same time as the first dose of intravenous hydralazine in the prenatal period.[61]

If second-line alternatives are required, the choice of agent should be discussed with an appropriate subspecialist in fetal-maternal medicine or critical care.​​ Availability of drugs and local experience with individual drugs are likely to influence the choice of treatment.[54]

In pregnancy, ACE inhibitors or angiotensin-II receptor antagonists are avoided due to potential teratogenic effects, and nitroprusside is avoided due to its potential for fetal cyanide poisoning.[1]​​ Renin inhibitors are also contraindicated.[1]

The American College of Obstetricians and Gynecologists (ACOG) recommends antihypertensive therapy for women with preeclampsia and a sustained SBP ≥160 mmHg or diastolic BP ≥110 mmHg.[48]​ However, thresholds for treatment vary internationally, with lower thresholds recommended by a number of societies.[100]​ The UK National Institute for Health and Care Excellence recommends treatment if BP remains above 140/90 mmHg.[61]​​

Although some of the available literature suggests that antihypertensive agents should be administered within 30-60 minutes, it is recommended that antihypertensive therapy begin as soon as reasonably possible after the criteria for acute onset severe hypertension are met.[48] It should be noted, however, that there are no trials supporting these suggested thresholds, and treatments should be tailored to individual patient circumstances. Specialist advice should be sought. 

Magnesium sulfate is not recommended as an antihypertensive agent, but remains the drug of choice for treatment of eclampsia and/or seizure prophylaxis for women with acute-onset severe hypertension during pregnancy and the postpartum period.[48]​ 

See Preeclampsia (Management approach).

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