Very high systemic arterial blood pressure

Hypertensive emergency (HE) is a severe elevation in systemic blood pressure combined with new or progressive end-organ damage most frequently in the cardiac, renal, and central nervous systems. HE is an infrequent clinical presentation of acute hypertension that requires immediate, titrated blood pressure reduction. Although HE is often associated with a blood pressure elevation >180/110 mm Hg, the diagnosis of HE is based upon the patient’s clinical signs and symptoms rather than a specific blood pressure measurement. Clinical conditions associated with HE include hypertensive encephalopathy, intracranial hemorrhage (IH), acute coronary syndrome, acute pulmonary edema, aortic dissection, acute renal failure, and eclampsia.

The term hypertensive urgency (HU) has been historically used to describe critically elevated blood pressure (>180/110 mm Hg) without evidence for acute and progressive dysfunction of target organs. In HU, a more gradual reduction of blood pressure over several hours to days is the therapeutic target. A rapid decrease in blood pressure in HU has no proven benefit, and cerebral or myocardial ischemia can be induced by aggressive antihypertensive therapy if the blood pressure falls below a level needed to maintain adequate tissue perfusion. HU can progress to end-organ damage if blood pressure remains uncontrolled over a sustained interval. As urgent, titrated therapy is indicated only in patients with end-organ damage (i.e., HE), some groups divide high systemic arterial blood pressure into the two categories of HE and uncontrolled hypertension. The majority of hospitalized patients with an elevation in systemic arterial blood pressure have uncontrolled hypertension.

A 25-institution US analysis of patients with HE reported a hospital mortality rate of 6.9%, with an aggregate 90-day mortality rate of 11% and a 90-day readmission rate of 37%. Although the frequency of hospitalization for HE might be increasing, the all-cause hospital mortality for these patients continues to decrease.

Malignant hypertension refers to HE with advanced retinopathy, defined as flame-shaped hemorrhages, cotton wool spots, or papilledema. Thrombotic microangiopathy is an HE with active Coombs-negative hemolysis and thrombocytopenia in the absence of another cause, that improves with the lowering of the blood pressure.

Pathophysiology

An acute elevation in systemic arterial blood pressure fundamentally involves an increase in systemic vascular resistance. This increase in vascular resistance results from a complex interaction of vascular mediators with a triggering factor in the setting of preexisting hypertension. Vasoconstriction can be promoted by circulating catecholamines, angiotensin II (ATII), vasopressin, thromboxane (TxA ₂ ), and endothelin 1 (ET1). In contrast, compensatory production of local counterregulatory vasodilators, including nitric oxide (NO) and prostacyclin (PGI ₂ ), is inadequate to maintain homeostatic balance. The early stage of HE is associated with a pressure-induced natriuresis that further stimulates the release of vasoconstrictor substances from the kidney.

Specific cellular mechanisms of vascular injury in HE involve proinflammatory responses incorporating cytokine secretion, monocyte activation, and upregulation of endothelial adhesion molecules. These proinflammatory factors extend the endothelial injury by promoting endothelial permeability and activating the coagulation cascade.

This cascade of intravascular events leads to the characteristic pathologic findings of obliterative vascular lesions. The vascular changes, evident to the clinician during an examination of the retina, are mirrored by similar changes in the kidney, leading to proliferative arteritis and, in advanced stages of the process, fibrinoid necrosis. A state of relative ischemia results in the affected organs, leading to end-organ dysfunction. The thrombotic microangiopathy (TMA) that characterizes the advanced stages of HE is a prothrombotic state characterized by endothelial dysfunction, platelet activation, and thrombin generation, with enhanced fibrinolytic activity.

The potential adverse effects of aggressive blood pressure control have been most carefully studied in the cerebral circulation. The cerebrovascular arteriolar tone is adjusted over a range of cerebral perfusion pressures (CPPs) to maintain constant cerebral blood flow (CBF). Increases in CPP promote an increase in vascular resistance, whereas decreases in CPP act to vasodilate the cerebral vasculature. Steady flow is therefore maintained over a range of mean arterial pressure (MAP) from approximately 60 mm Hg to 150 mm Hg. As MAP increases to values >180 mm Hg or above the upper limit of autoregulation, cerebral hyperperfusion, can occur, resulting in cerebral edema. Conversely, when CPP falls below the lower limit of autoregulation, CBF decreases, and tissue ischemia may occur. In patients with long-standing hypertension, a rightward shift of the CPP–CBF relationship occurs such that the lower limit of autoregulation occurs at a value higher than that in normal subjects. Comparative studies in hypertensive and normotensive patients suggest that the lower limit of autoregulation is about 20% below the resting MAP for both, although the absolute value is higher for the hypertensive patient. These data support the standard recommendation that a safe level of blood pressure reduction in HE is a 10% to 20% reduction of MAP from the highest values on clinical presentation, or a diastolic blood pressure typically in the 100 to 110 mm Hg range.

Clinical presentation

The history and physical examination in the patient with an acute elevation in systemic arterial blood pressure will focus on signs and symptoms of acute organ dysfunction. No specific blood pressure threshold defines an HE. At identical blood pressure levels, end-organ damage may be present or absent.

According to the Studying the Treatment of Acute Hypertension (STAT) registry, the most common presenting symptoms in HE include shortness of breath (29%), chest pain (26%), headache (23%), altered mental status (20%), and a focal neurologic deficit (11%). The most common admitting diagnoses are severe hypertension (27%), subarachnoid hemorrhage (11%), acute coronary syndrome (10%), and heart failure (8%). In approximately 25% of patients with HE, there is a history of either chronic or current medication nonadherence, and 11% of patients are current drug abusers. The mean systolic blood pressure in the STAT registry was 200 mm Hg (interquartile range [IQR], 186–220), and the median diastolic blood pressure was 110 mm Hg (IQR, 93–123).

The patient evaluation must include a detailed medication history with attention to medications associated with blood pressure elevation (e.g., nonsteroidal antiinflammatory drugs [NSAIDs], calcineurin inhibitors, sympathomimetics). For patients with preexisting hypertension, the possibility of hypertensive medication nonadherence and withdrawal is considered.

HEs may develop as secondary hypertension in association with such diverse etiologies as renal vascular disease, sleep apnea, hyperaldosteronism, pheochromocytoma, and pregnancy (preeclampsia). Also, illicit drug use is a significant risk factor for the development of HEs.

Blood pressure should be measured in both arms using an appropriately sized cuff and in a lower limb to detect differences associated with aortic dissection. Repeated blood pressure measurements are indicated, as a significant fraction of patients will resolve hypertension with bed rest and initial observation. Physical examination, including a fundoscopic examination, should focus on the identification of signs suggesting end-organ dysfunction.

Hypertension and cerebrovascular disease

Hypertensive encephalopathy

Acute elevations in systemic arterial blood pressure can lead to hypertensive encephalopathy (HEN). The clinical manifestations of HEN include headache, confusion, or a depressed level of consciousness; nausea and vomiting; visual disturbances (cortical blindness); or seizures (generalized or focal). Patients may present with focal neurologic deficits, although this finding is more common in cerebrovascular accidents. Rarely, HEN can show brainstem involvement manifesting as ataxia and diplopia. If left untreated, the condition can progress to coma and death. Retinal findings, including arteriolar spasm, exudates or hemorrhages, and papilledema, may be present but are not a requirement. Magnetic resonance imaging (MRI) studies show edema involving the subcortical white matter of the parieto-occipital regions best seen on T2 and fluid-attenuated inversion recovery (FLAIR) imaging; a finding termed posterior leukoencephalopathy . Approximately two-thirds of patients will also have hyperintense lesions on T2 and FLAIR imaging in the frontal and temporal lobes, and one-third will have brainstem, cerebellum, or basal ganglia involvement. The imaging findings are typically bilateral but can be asymmetric. HEN is the most common cause of reversible posterior leukoencephalopathy syndrome (RPLS). Improvement or resolution of the radiographic findings is often delayed in comparison with clinical improvement.

The diagnosis of HEN is confirmed by the absence of other conditions and the prompt resolution of symptoms and neuroimaging abnormalities with effective blood pressure control. The failure of a patient to improve within 6–12 hours of blood pressure reduction should suggest an alternative cause of the encephalopathy. The condition is typically reversible with no observable adverse outcomes.

Acute stroke

As blood pressure management differs significantly between acute ischemic stroke and acute hemorrhagic stroke, early imaging is required to guide treatment. The majority of patients with acute ischemic stroke have elevated systolic blood pressure on presentation to the hospital that declines to normal within 48 hours of presentation. Current data are contradictory whether hypertension in the early phase of acute stroke contributes to a worse patient outcome or is a surrogate marker of stroke severity.

During an acute stroke, cerebral autoregulation may be compromised in ischemic tissue, and lowering of blood pressure may further compromise CBF and extend ischemic injury. Medications used to treat hypertension may lead to cerebral vasodilation, augmenting CBF and leading to progression in cerebral edema. Ideally, a “correct” level of MAP should be maintained in each stroke patient to maintain CPP without worsening cerebral edema or progression of the lesion. Still, the clinical determination of this ideal value is often difficult.

Consensus guidelines recommend that blood pressure not be treated acutely in the patient with ischemic stroke unless the hypertension is extreme (systolic blood pressure >220 mm Hg or diastolic blood pressure >120 mm Hg) or the patient has active end-organ dysfunction in other organ systems. ^, When treatment is indicated, cautious lowering of blood pressure by approximately 15% during the first 24 hours after stroke onset is suggested. Antihypertensive medications can be restarted at around 24–48 hours after stroke onset in patients with preexisting hypertension who are neurologically stable unless a specific contraindication to restarting treatment exists. Special considerations are patients with extracranial or intracranial stenosis and candidates for thrombolytic therapy. The former group may be critically dependent on perfusion pressure so that blood pressure therapy may be further delayed. In contrast, treatment is recommended before lytic treatment is started, so that systolic blood pressure is ≤185 mm Hg and diastolic blood pressure is ≤110 mm Hg before lytic therapy administration. ^, The blood pressure should be stabilized and maintained below 180/105 mm Hg for at least 24 hours after intravenous (IV) lytic therapy.

Blood pressure is frequently elevated in patients with acute IH, often to a greater degree than seen in ischemic stroke. Theoretically, severe elevations in blood pressure may worsen IH by creating a continued force for bleeding. However, the increased arterial pressure may also be necessary to maintain cerebral perfusion in this setting, and aggressive blood pressure management could lead to worsening cerebral ischemia. For patients with suspected elevated intracranial pressure (ICP), ICP monitoring may be indicated to help maintain CPP during therapeutic interventions. American Heart Association guidelines, admittedly arbitrary and not evidence-based, suggest a target MAP of less than 110 mm Hg or a blood pressure of less than 160/90 mm Hg while maintaining a reasonable CPP in patients with suspected elevated ICP. Based upon the results of INTERACT 1 and 2—which showed a decreasing trend in the primary outcome of death or severe disability, significant improvements in secondary functional outcomes, and reassuring safety data—many investigators advocate acute blood pressure reduction to a target systolic blood pressure of ∼140 mm Hg for patients with spontaneous IH.

Hypertension and cardiovascular disease

Acute coronary syndrome

Patients presenting with acute myocardial ischemia or infarction frequently suffer from an elevated MAP. The increased afterload raises the myocardial oxygen demand. Decreasing the heart rate and blood pressure in these patients will favorably reduce the myocardial oxygen demand and infarct size. However, a reduction in arterial pressure in this setting should be made cautiously. Potent systemic vasodilation without coronary vasodilation can lead to a decrease in coronary artery perfusion pressure and infarct extension. For this reason, nitroglycerin (NTG), a robust coronary vasodilator, is often the antihypertensive agent of choice in acute coronary syndromes. In combination with beta-blocker therapy, this approach can reduce cardiac workload significantly in the setting of ischemia.

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