Patients with a systolic BP (SBP) > 179 mm Hg or a diastolic BP (DBP) > 109 mm Hg are usually considered to be having a “hypertensive crisis.”
Severe elevations in BP were classified as hypertensive emergencies in the presence of acute end-organ damage or as hypertensive urgencies in the absence of acute target-organ involvement. Patients with hypertensive urgency should have their BP reduced within 24 to 48 h, whereas patients with hypertensive emergency should have their BP lowered immediately, although not to “normal” levels.
The absolute level of BP may not be as important as the rate of increase. For example, in patients with long-standing hypertension, a SBP of 200 mm Hg or a DBP up to 150 mm Hg may be well tolerated without the development of hypertensive encephalopathy; whereas in children and pregnant women, encephalopathy may develop with a DBP of only 100 mm Hg.
- Hypertensive encephalopathy
- Acute aortic dissection
- Acute myocardial infarction
- Acute coronary syndrome
- Pulmonary edema with respiratory failure
- Severe pre-eclampsia, HELLP syndrome, eclampsia
- Acute renal failure
- Microangiopathic hemolytic anemia
A focused medical history that includes the use of any prescribed or over-the-counter medications, their hypertensive history, previous control, current antihypertensive medications with dosing, adherence with their medication regimen, and the time from last dose are important facts to acquire prior to initiating treatment. Inquiry into the use of recreational drugs should be made.
The physical examination should attempt to identify evidence of end-organ damage by assessing pulses in all extremities, auscultating the lungs for evidence of pulmonary edema, the heart for murmurs or gallops, the renal arteries for bruits, and performing a focused neurologic and fundoscopic examination. Headache and altered level of consciousness are the usual manifestations of hypertensive encephalopathy. Cardiac evaluation should aim to identify angina or myocardial infarction with the focus on clarifying any atypical symptoms such as dyspnea, cough, or fatigue that may be overlooked. If the clinical picture is consistent with aortic dissection (severe chest pain, unequal pulses, widened mediastinum), a contrast CT scan or MRI of the chest should be obtained promptly to rule out aortic dissection.
The initial evaluation needs to include at least a complete blood count (rule out hemolysis), chemistry basic panel (acute renal insufficiency), urine analysis, chest radiograph (congestive heart failure or aortic dissection), and ECG (cardiac ischemia). Appropriate ordering of CT scan of the head or chest can be considered as well as cardiac echocardiography, depending on the circumstances.
Initial Management of BP
Hypertensive Urgency: The majority of patients have SBP > 180 mm Hg, DBP >110 mm Hg but has no end-organ damage. In these patients, utilizing oral medications to lower the BP gradually over 24 to 48 h is the best approach to management. Rapid correction of severely elevated BP below the auto regulatory range of these vascular beds can result in marked reduction in perfusion causing ischemia and infarction. Therefore, although the BP must be reduced in these patients, it must be lowered in a slow and controlled fashion to prevent organ hypoperfusion.
Hypertensive Emergency: Altered auto regulation also occurs in patients with hypertensive emergency, and since end-organ damage is present already, rapid and excessive correction of the BP can further reduce perfusion and propagate further injury. Therefore, patients with a hypertensive emergency are best managed with a continuous infusion of a short-acting, titratable antihypertensive agent.
The immediate goal is to reduce DBP by 10 to 15% (at the most 20-25%) or to approximately 110 mm Hg over a period of 30 to 60 min. Then, target their SBP to 150-160 in the next 24 hrs.
In patients with aortic dissection, the BP should be reduced rapidly (within 5 to 10 min), targeting a SBP of < 120 mm Hg and mean arterial pressure (MAP) <80 mm Hg. An important consideration prior to initiating IV therapy is to assess the patient’s volume status. Due to pressure natriuresis, patients with hypertensive emergencies may be volume depleted, and restoration of intravascular volume with IV saline solution will serve to restore organ perfusion and prevent a precipitous fall in BP when anti hypertensive regimens are initiated.
Preferred Antihypertensive Agents:
- Acute pulmonary edema/systolic dysfunction: Nicardipine, fenoldopam, or nitroprusside in combination with nitroglycerin and a loop diuretic
- Acute pulmonary edema/diastolic dysfunction : Esmolol, metoprolol, labetalol, or verapamil in combination with low-dose nitroglycerin and a loop diuretic
- Acute myocardial ischemia: Labetalol or esmolol in combination with nitroglycerin
- Hypertensive encephalopathy: Nicardipine, labetalol, or fenoldopam
- Acute aortic dissection: Labetalol or combination of nicardipine and esmolol or combination of nitroprusside with either esmolol or IV metoprolol
- Pre-eclampsia, eclampsia: Labetalol or nicardipine
- Acute renal failure/microangiopathic anemia : Nicardipine or fenoldopam
- Sympathetic crisis/cocaine overdose: Verapamil, diltiazem, or nicardipine in combination with a benzodiazepine. Never use a betablocker alone.
- Acute post operative hypertension : Esmolol, nicardipine, or labetalol
- Acute ischemic stroke/intracerebral bleed : Nicardipine, labetalol, or fenoldopam
Pharmacologic Agents Used in the Treatment of Hypertensive Emergencies
The preferred agents include labetalol, esmolol, nicardipine, and fenoldopam. Oral and sublingual nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommend. Clonidine and angiotensin-converting enzyme (ACE) inhibitors are long acting and poorly titratable. Nifedipine, nitroglycerin, and hydralazine are not recommended in the management of hypertensive emergencies.
Labetalol: Labetalol is a combined selective alpha-adrenergic and nonselective beta- blocker with 1:7 ratio as IV and 1:3 as oral route. It has more potent beta action than alpha. Labetalol is metabolized by the liver to form an inactive glucuronide conjugate. The hypotensive effect of labetalol begins within 2 to 5 min after its IV administration, reaching a peak at 5 to 15 min following administration, and lasting for about 2 to 4 h. Due to its beta-blocking effects, the heart rate is either maintained or slightly reduced. Unlike pure beta- blocking agents that decrease cardiac output, labetalol maintains cardiac output. Labetalol reduces the systemic vascular resistance without reducing total peripheral blood flow. In addition, the cerebral, renal, and coronary blood flow is maintained. This agent has been used in the setting of pregnancy induced hypertensive crisis because little placental transfer occurs.
Labetalol may be administered as loading dose of 20 mg, followed by repeated incremental doses of 20 to 80 mg at 10-min intervals until the desired BP is achieved. Alternatively, after the initial loading dose, an infusion commencing at 1 to 2 mg/min and titrated up to until the desired hypotensive effect is achieved.
Nicardipine: Nicardipine is a second-generation calcium-channel blocker with high vascular selectivity and strong cerebral and coronary vasodilatory activity. The onset of action of IV nicardipine is from 5 to 15 min, with duration of action of 4 to 6 h. IV nicardipine has been shown to reduce both cardiac and cerebral ischemia. This medication is contraindicated in patients with advanced aortic stenosis.
The nicardipine dosage is independent of the patient’s weight, with an initial infusion rate of 5 mg/h to a maximum of 15 mg/h until the desired BP reduction is achieved. Increase infusion rate by 2.5mg/hr and can be increased every 5-15 mins.
Esmolol is an ultra short-acting cardioselective, beta- blocking agent. The onset of action of this agent is within 60 s, with duration of action of 10 to 20 min. Half life of esmolol is between 5-9 mins. The metabolism of esmolol is via rapid hydrolysis of ester linkages by RBC esterases and is not dependant on renal or hepatic function. Esmolol is particularly useful in severe postoperative hypertension.
It is administered as a 0.5 to 1 mg/kg loading dose over 1 min, followed by an infusion starting at 50 mcg/kg/ min and increasing up to 300 mcg/kg/min as necessary.
Fenoldopam is unique among the parenteral BP agents because it mediates peripheral vasodilation by acting on peripheral dopamine-1 receptors. Fenoldopam is rapidly and extensively metabolized by conjugation in the liver, without participation of cytochrome P-450 enzymes. The onset of action is within 5 min, with the maximal response being achieved by 15 min. The duration of action is from 30 to 60 min, with the pressure gradually returning to pretreatment values without rebound once the infusion is stopped.
Fenoldopam improves creatinine clearance, urine flow rates, and sodium excretion in severely hypertensive patients with both normal and impaired renal function.
Sodium nitroprusside is an arterial and venous vasodilator that decreases both afterload and preload. Nitroprusside decreases cerebral blood flow while increasing intracranial pressure, effects that are particularly disadvantageous in patients with hypertensive encephalopathy or following a cerebrovascular accident.
Nitroprusside is a very potent agent, with an onset of action of seconds, duration of action of 1 to 2 min, and a plasma half-life of 3 to 4 min. Due to its potency, rapidity of action, and the development of tachyphylaxis, we recommend intraarterial BP monitoring.
Nitroprusside may cause cytotoxicity due to the release of cyanide with interference of cellular respiration. Cyanide toxicity has been documented to result in “unexplained cardiac arrest,” coma, encephalopathy, convulsions, and irreversible focal neurologic abnormalities. Considering the potential for severe toxicity with nitroprusside, this drug should only be used for as short periods as possible, and the infusion rate should not be > 2 mcg/kg/min. The cyanide toxicity is related more to the rate of infusion than the total dose. Cyanide toxicity is treated with sodium thiosulphate.
Clevidipine is third-generation calcium-channel blocker and is an ultra short-acting selective arteriolar vasodilator. Similar to esmolol, it is rapidly metabolized by RBC esterases; thus, its metabolism is not affected by renal or hepatic function.
Clevidipine reduces BP by a direct and selective effect on arterioles, thereby reducing afterload without affecting cardiac filling pressures or causing reflex tachycardia.
An IV infusion at 1–2 mg/hour is recommended for initiation and should be titrated by doubling the dose every 90 seconds. As the blood pressure approaches goal, increase the dose by less than doubling and lengthen the time between dose adjustments to every 5-10 minutes. An approximately 1-2 mg/hour increase will generally produce an additional 2-4 mmHg decrease in systolic pressure..The maximum infusion rate for Clevidipine is 32 mg/hour
Although nifedipine has been administered via the sublingual route, the drug is poorly soluble and is not absorbed through the buccal mucosa. It is however rapidly absorbed from the GI tract after the capsule is broken/dissolved. Sudden uncontrolled and severe reductions in BP accompanying the administration of nifedipine may precipitate cerebral, renal, and myocardial ischemic events that have been associated with fatal outcomes.
Nitroglycerin, Hydralazine, and Diuretics
Nitroglycerin is a potent venodilator and only at high doses affects arterial tone. It causes hypotension and reflex tachycardia, which are exacerbated by the volume depletion characteristic of hypertensive emergencies. Nitroglycerin reduces BP by reducing preload and cardiac output; Low-dose administration may be used as an adjunct to IV antihypertensive therapy in patients with hypertensive emergencies associated with acute coronary syndromes or acute pulmonary edema.
Hydralazine is a direct-acting vasodilator. Following IM or IV administration, there is an initial latent period of 5 to 15 min followed by a progressive and often precipitous fall in BP that can last up to 12 h. It can also cause reflex tachycardia. It's half life is very prolonged especially in patients with kidney dysfunction.
Volume depletion is common in patients with hypertensive emergencies, and the administration of a diuretic together with a hypertensive agent can lead to a precipitous drop in BP. Diuretics should be avoided unless specifically indicated for volume overload, as occurs in renal parenchymal disease or coexisting pulmonary edema.
Captopril is the fastest-acting ACE inhibitor with an onset of action of 15 min. It can induce a reliable drop in the BP that lasts for 4 to 6 h. The starting dose is 6.25 mg.
Clonidine is a central-acting a2 agonist. It induces a decrease in the sympathetic tone with a significant reduction in BP. It can also cause sedation and is most useful in patients with drug or alcohol withdrawal. Doses start at 0.1 mg/h.
A rebound effect has been reported on discontinuation. This side effect is worsened with concomitant b-blockade therapy.
Acute Aortic Dissection:
Propagation of the dissection is dependent not only on the elevation of the BP itself but also on the velocity of left ventricular ejection. The combination of a beta-blocker and vasodilator is the standard approach to treatment. Esmolol is the beta blocker of choice with metoprolol as a suitable alternative. Nicardipine or fenoldopam are equally effective alternatives. Unless significant medical comorbidities are present, surgery is indicated for all patients with type A dissection. Patients with type B dissections and distal aortic dissections can be managed medically with aggressive BP control.
The vast majority of patients with cerebral ischemia present with acutely elevated BP regardless of the subtype of infarct or preexisting hypertension. The BP elevation decreases spontaneously over time. The elevated BP is not a manifestation of a hypertensive emergency but rather a protective physiologic response to maintain cerebral perfusion pressure to the vascular territory affected by ischemia. Lowering the BP in patients with ischemic strokes may reduce cerebral blood flow, which because of impaired auto regulation, may result in further ischemic injury.
Stroke guidelines recommend withholding antihypertensive therapy for acute ischemic stroke unless there is planned thrombolysis, evidence of concomitant noncerebral acute organ damage, or if the BP is excessively high, SBP >220 mm Hg or a DBP >120 mm. In these patients, the aim is to reduce the pressure by not more than 10 to 15% in the first 24 h. In patients receiving thrombolytic therapy, antihypertensive therapy is required for SBP >185 mm Hg or DBP >110 mm Hg, with a targeted SBP of 180 mm Hg and a DBP of 105 mm Hg. Nicardipine has been demonstrated to be an effective agent for the control of BP in patients with intracerebral hemorrhage.
Preeclampsia and Eclampsia
Initial therapy of preeclampsia includes volume expansion, magnesium sulfate (MgSO4) for seizure prophylaxis and BP control. Delivery is the definitive treatment for preeclampsia and eclampsia. Magnesium sulfate is usually administered as a loading dose of 4 to 6 g, followed by a constant infusion of 1 to 2 g/h of MgSO4 depending on urine output and deep tendon reflexes, which are checked on an hourly basis.
Current guidelines recommend keeping SBP from 140 to 160 mm Hg and DBP from 90 to 105 mm Hg.
Hydralazine has been recommended as the drug of choice to treat severe preeclampsia and eclampsia since the early 1970. However, hydralazine has side effects such as headache, nausea, and vomiting that are common and mimic symptoms of deteriorating preeclampsia. Most importantly, it has a delayed onset of action, an unpredictable hypotensive effect, and a prolonged duration of action. These properties may result in a precipitous hypotensive overshoot compromising both maternal cerebral blood flow and uteroplacental blood flow. Hence, hydralazine should not be used as first-line treatment of severe hypertension in pregnancy.
Ideal choice is IV labetalol or nicardipine, which are easier to titrate and have a more predictable dose response than hydralazine.
The most commonly encountered sympathetic crises are related to the recreational use of sympathomimetic drugs such as cocaine, amphetamine, or phencyclidine. Rarely, these crises may be seen with pheochromocytoma, patients receiving a monoamine oxidase inhibitor who ingest a tyramine-containing food, or patients who abruptly stop antihypertensive medications such as clonidine or beta blockers.
In the clinical situations characterized by sympathetic overstimulation, beta blockers should be avoided to prevent vascular beta-receptor antagonism resulting in unopposed alpha-adrenergic activity and potential increase in BP. In fact, in cocaine- induced hypertensive emergency, the use of beta-adrenergic blockade can increase coronary vasoconstriction, fail to control heart rate, increase BP, and decrease survival.
BP control is best achieved with nicardipine, fenoldopam, or verapamil in combination with a benzodiazepine. Phentolamine is an alternative agent.
- Always be careful in resuming all oral antihypertensives at the same time. Some of these patients are non compliant and may not be taking all these medications. Resuming all of them at once may lead to severe hypotension.