Uncontrolled Hypertension

Although hypertension is defined as a blood pressure of > 130/80 mm Hg, individuals can present with comorbidities of severe asymptomatic or “uncontrolled” hypertension (≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic) that carries with it a significant risk of morbidity and mortality. Despite the prolonged presence of hypertension, there may be no signs or symptoms of end-organ damage (e.g., brain, eyes, heart, kidneys) until function becomes decompensated or severely impaired. Individuals may present with clinical symptoms such as chest pain due to MI or focal neurologic changes associated with a cerebral infarction or intracranial hemorrhage. Diagnosis is made using serial blood pressure measurements and testing for end-organ damage. Management includes lowering the blood pressure and treating specific organ damage.

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Overview

Definitions and classification

  • Severe hypertension (hypertensive crisis): 
    • A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic
    • May occur in previously undiagnosed or known hypertensive individuals
    • May be isolated or sustained
    • A clinical spectrum:
      • Hypertensive urgency: asymptomatic, or relative asymptomatic, severe hypertension without end-organ damage
      • Hypertensive emergency: severe hypertension associated with signs of end-organ damage
  • Resistant hypertension: Blood pressure that remains uncontrolled despite concurrent use of 3 antihypertensive agents of different classes:
    • Of these agents, 1 must be a diuretic (or a diuretic was not tolerated).
    • All must be dosed at the maximum allowable (or tolerable) dose.
    • Blood pressureP that is controlled on maximal doses of ≥ 4 medications belong to this class by default.
  • Refractory hypertension:
    • Blood pressure that cannot be controlled even with maximally tolerated doses of ≥ 5 drugs
    • Must include chlorthalidone
    • Must include spironolactone
  • Secondary hypertension:
    • Resistant hypertension with an identifiable and potentially treatable etiology
    • Renal artery stenosis (RAS)
    • Primary hyperaldosteronism
    • CKD
    • Obstructive sleep apnea (OSA)
    • Pheochromocytoma
    • Cushing syndrome
    • Coarctation of the aorta

Etiology

  • Head trauma
  • Blood pressure medication noncompliance
  • Suboptimal therapy
  • Rebound hypertension
  • Emotional disturbance
  • Hyperthyroidism
  • Extracellular volume expansion: 
    • High-sodium diet
    • Underlying renal insufficiency
    • Sodium retention (side effect of vasodilators)
  • Use of stimulants:
    • Cocaine
    • Methamphetamine
    • Caffeine 
    • Nicotine
  • Medications that cause increased blood pressure:
    • NSAIDs
    • Sympathomimetics:
      • Weight-loss drugs
      • Decongestants
      • Amphetamines
    • Glucocorticoids
    • Oral contraceptives
    • Antidepressants
    • Calcineurin inhibitors
  • Causes of secondary hypertension

Epidemiology

  • Difficult to assess because of inconsistent coding practices among practitioners/institutions
  • Depends on the underlying cause

Pathophysiology

  • Poorly understood
  • Depends on the underlying cause

Clinical Presentation

Regardless of the manifestation of severe hypertension, by definition, the individual will have a blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic.

Hypertensive urgency

  • Blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic
  • Asymptomatic or vague/minimal symptoms:
    • Headache
    • Fatigue
    • Flushing
    • Blurred vision

Hypertensive emergency

  • Blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic
  • Potential symptoms:
    • Chest pain
    • Shortness of breath
    • Visual disturbance
    • Focal neurologic symptoms
    • Altered mental status
    • Hematuria
    • Anuria
  • Evidence of myocardial ischemia or MI:
    • Diagnostic ECG changes
    • Elevated cardiac enzymes
    • Acute and/or decompensated heart failure
  • Evidence of cerebrovascular accident:
    • Focal neurologic deficits
    • CT/MRI findings indicative of cerebral ischemia and/or bleeding
  • Evidence of acute/acute-on-chronic renal failure:
    • Acute uremia
    • Acidosis/alkalosis
    • Abnormal electrolytes

Evaluation and Diagnosis

During the initial assessment of a individual with severe hypertension, it is imperative to exclude chronic target-organ damage. Severe elevations in blood pressure should be quickly confirmed with repeat measurement.

History

Particular focus on risk factors for end-organ vascular events:

  • Acute head injury
  • Use of stimulant drugs (cocaine, methamphetamine)
  • Known myocardial ischemia
  • Known cerebrovascular ischemia
  • Known arterial deformity:
    • Abdominal aortic aneurysm (AAA)
    • Cerebral aneurysm
    • Arteriovenous malformation (AVM)
    • Recent vascular surgery
    • RAS
  • Multiple vascular risk factors:
    • Age
    • Family history
    • Smoking
    • Diabetes
    • Hypertension
    • Dyslipidemia
    • Obesity
    • Sedentary lifestyle
    • OSA

Symptoms of end-organ dysfunction:

  • Headache
  • Fatigue
  • Blurred vision
  • Chest pain
  • Shortness of breath
  • Nausea/vomiting (increased intracranial pressure)
  • Visual disturbance
  • Focal neurologic symptoms
  • Altered mental status
  • Acute severe back pain (aortic dissection)
  • Hematuria
  • Anuria

Physical examination

  • Blood pressure evaluation:
    • Standard blood pressure measurement with a manual sphygmomanometer at regular intervals is appropriate for low-risk individuals.
    • Higher-risk individuals may need continuous monitoring with an automatic sphygmomanometer with a digital display.
    • Individuals requiring urgent and controlled blood pressure lowering with IV antihypertensives may benefit from the placement of an intraarterial catheter for continuous blood pressure monitoring.
  • Mental status:
    • Agitation
    • Delirium
    • Stupor
    • Seizure
    • Coma
  • Focal neurologic findings:
    • Visual loss
    • Limb paresis/paralysis
    • Speech deficit
  • Ophthalmic exam:
    • Hemorrhages
    • Exudates
    • Papilledema
  • Signs of cardiac decompensation:
    • Jugular venous distention (JVD)
    • Palpitations/abnormal rhythm
    • New murmur
    • New gallop
    • Pulmonary rales
    • Peripheral edema
  • Miscellaneous:
    • Abdominal bruit (AAA or RAS)
    • Carotid or femoral bruit (suggests atherosclerosis)

Diagnostic tests

  • ECG
  • Urine studies:
    • Urinalysis
    • 24-hour urine collection:
      • Protein
      • Catecholamines/metanephrines for pheochromocytoma
      • Sodium excretion
  • Blood chemistry:
    • Electrolytes
    • Serum creatinine
    • Cardiac biomarkers
    • Serum aldosterone

Imaging for ischemia/vascular compromise

  • Chest X-ray:
    • Pulmonary edema
    • Cardiac enlargement
    • Widened mediastinum
    • Pulmonary edema
  • CT/MRI brain:
    • Cerebral ischemia
    • Cerebral hemorrhage
  • CT chest/abdomen:
    • Thoracic aortic dissection
    • Abdominal aortic aneurysm dissection

Management

Rate of reduction for elevated blood pressure

  • Target blood pressure should be achieved over a period of hours to days.
  • Slower reductions may be needed in older individuals with an increased risk of cerebral or myocardial ischemia.

Target blood pressure

  • Blood pressure should be slowly reduced to < 160/< 100 mm Hg.
  • Mean arterial pressure (MAP) should not be lowered >25%–30% in the 1st few hours.
  • Long-term reductions back to previous therapeutic target (i.e., ≤ 130/80 mm Hg)

No evidence of end-organ damage

Outpatient management:

  •  Outcomes may be poor:
    • High rate of loss to follow-up soon after evaluation
    • High rate of return to the ED for recurrent uncontrolled hypertension within 3 months
  • May be appropriate if:
    • No evidence of end-organ damage
    • Blood pressure was previously controlled on an antihypertensive regimen.
    • Individual or their caregiver is reliable for monitoring blood pressure and ensuring that medications are taken.

ED management:

  • Move individual to a quiet room: can lead to a fall in systolic pressure of ≥ 10–20 mm Hg 
  • Determine time course of blood pressure lowering:
    • Balance between 2 concerns:
      • Blood pressure ↓ too quickly, potential inability for autoregulation to maintain end-organ tissue perfusion
      • Blood pressure ↓ too slowly, potential risk of imminent cardiovascular events 
  • If blood pressure needs to be lowered quickly (hours):
    • Includes individuals with high risk:
      • Imminent coronary or cerebral ischemia
      • Known renal artery stenosis
      • Known existing cerebral or aortic aneurysm
    • Oral clonidine (rapid-acting)
    • Oral captopril (rapid-acting)
    • Oral or sublingual nitrates (rapid-acting)
    • Oral hydralazine (rapid-acting)
    • Consider admitting the individual for observation and blood pressure medication titration.
    • Consider discharge home with short-interval follow-up.
  • If blood pressure needs to be lowered slowly (days):
    • Previously diagnosed hypertension: 
      • Previously controlled → resume previous regimen
      • Previously suboptimally controlled → increase doses for previous regimen or add a new agent 
    • If new diagnosis:
      • Amlodipine 
      • Chlorthalidone 
      • Beta-blockers if the individual has a comorbid indication for beta-blockade (e.g., heart failure)
      • ACEis if the individual has a comorbid indication for ACE inhibition (e.g., diabetes)
      • Combination therapy may be considered.
      • Consider hospital admission for medication titration.
      • Consider discharge home with short-interval follow-up.
  • Prior to discharge:
    • Ensure:
      • Short-interval follow-up with primary care physician (PCP) or appropriate specialist
      • Prescription given for any new medications
    • Counsel:
      • Importance of adherence to blood pressure medication regimen
      • Importance of dietary sodium restriction

Evidence of end-organ damage

  • Admit individual to ICU:
    • For intensive monitoring
    • For rapid intervention in the event of decompensation
    • For rapidly titratable IV delivery of blood pressure medications
  • Rapid lowering of blood pressure is generally not advised.
    • Risk of ischemia if vascular physiology has habituated to higher blood pressure
    • 10%–20% lowering of MAP in the 1st hour
    • Additional lowering of MAP 5%–15% over the next 24 hours
  • Exceptions:
    • Ischemic stroke: Do NOT initiate blood pressure–lowering measures unless:
      • Blood pressure > 185/110 mm Hg if candidate for reperfusion
      • Blood pressure > 220/120 mm Hg if not candidate for reperfusion
    • Aortic dissection: Initiate rapid systolic blood pressure lowering.
    • Intracerebral hemorrhage: DO initiate rapid systolic blood pressure lowering: 
      • Target blood pressure 140 mm Hg if presenting blood pressure is 150–220 mm Hg
      • Target blood pressure 140–160 mm Hg if presenting blood pressure is >220 mm Hg
  • Appropriate specialist consultation:
    • Interventional cardiology
    • Neurology/neurosurgery
    • Vascular surgery
    • Interventional radiology
    • Nephrology
  • Therapeutic IV blood pressure agents:
    • Beta-blockers:
      • Labetalol
      • Esmolol
    • Calcium channel blockers:
      • Nicardipine
      • Clevidipine
      • Felodipine
    • Nitrates:
      • Nitroprusside
      • Nitroglycerine
    • Others:
      • Phentolamine
      • Hydralazine
  • After 8–24 hours of stable blood pressure control:
    • Transition to oral agents
    • Wean IV agents
    • Transition out of ICU
    • Discharge planning as above.

Clinical Relevance

  • Labile (paroxysmal) hypertension: marked elevations in blood pressure that are recurrent, sudden, and transient. Labile hypertension is linked to sympathetic hyperstimulation, though the link is poorly understood. Treatment is with adrenergic blocking agents (i.e., beta-blockers, alpha-blockers).
  • Secondary hypertension: resistant hypertension with an identifiable and potentially treatable etiology. Includes RAS, primary hyperaldosteronism, CKD, OSA, pheochromocytoma, Cushing syndrome, coarctation of the aorta. Treatment depends on the specific cause. 
  • Head trauma: complex cascade of neurohormonal factors resulting from a traumatic brain injury can cause severe hypertension. This cascade likely represents compensatory mechanisms to maintain cerebral perfusion in the setting of increased intracranial pressure. The balance between maintenance of cerebral perfusion and prevention of cerebrovascular events makes treatment of elevated blood pressure with head trauma controversial.  
  • Hypertensive encephalopathy: dramatic change in the level of consciousness, cognition, or personality in the setting of severe hypertension and attributable to cerebral edema. Management includes aggressive but careful lowering of the blood pressure and immediate neurologic/neurosurgical consultation to avoid or minimize cerebrovascular events and/or permanent brain damage.  
  • Hypertensive retinopathy: characterized by retinal hemorrhages, exudates, and papilledema in the setting of severe hypertension. Management consists of aggressive but careful lowering of the blood pressure and immediate ophthalmologic consultation to avoid or minimize vision loss. 
  • Hypertensive heart disease: Cardiomyopathy is directly attributable to the physiologic compensations the myocardium must make to maintain cardiac output in the face of chronically elevated afterload and may result in systolic dysfunction, diastolic dysfunction, valvular dysfunction, increased arrhythmogenic potential, and myocardial ischemia (even with normal coronary arteries). Management consists of blood pressure optimization and prevention of heart failure, arrhythmia, and ischemia. 
  • Hypertensive nephropathy: progressive nephrosclerosis involving the renal vasculature, glomeruli, and tubulointerstitial elements in the setting of uncontrolled hypertension. The long-term result is progressive loss of kidney function ultimately manifesting as end-stage renal disease that may require hemodialysis. 
  • Obstetric hypertensive complications: chronic hypertension, gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome are the obstetric complications of pregnancy that can pose health risks to the mother and fetus. Management includes control of blood pressure and delivery of the fetus.

References

  1. Varon, J., Elliot, W. (2020). Management of severe asymptomatic hypertension (hypertensive urgencies) in adults. UpToDate. Retrieved July 10, 2021, from https://www.uptodate.com/contents/management-of-severe-asymptomatic-hypertension-hypertensive-urgencies-in-adults
  2. Varon, J., Elliot, W. (2021). Evaluation and treatment of hypertensive emergencies in adults. UpToDate. Retrieved July 10, 2021, from https://www.uptodate.com/contents/evaluation-and-treatment-of-hypertensive-emergencies-in-adults
  3. Townsend, R. (2020). Definition, risk factors, and evaluation of resistant hypertension. UpToDate. Retrieved July 10, 2021, from https://www.uptodate.com/contents/definition-risk-factors-and-evaluation-of-resistant-hypertension
  4. Mann, S. (2019). Labile hypertension. UpToDate. Retrieved July 10, 2021, from https://www.uptodate.com/contents/labile-hypertension
  5. Varon, J., Elliot, W. (2019). Drugs used for the treatment of hypertensive emergencies. UpToDate. Retrieved July 10, 2021, from https://www.uptodate.com/contents/drugs-used-for-the-treatment-of-hypertensive-emergencies

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