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Hypertensive urgencies and emergencies 

Hypertensive urgencies and emergencies
Hypertensive urgencies and emergencies

Gregory Y.H. Lip

, and Alena Shantsila

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date: 07 March 2021


Hypertensive urgencies and emergencies occur most commonly in patients with previous hypertension, especially if inadequately managed. About 40% of cases have an underlying cause, most commonly renovascular disease, primary renal diseases, phaeochromocytoma, and connective tissue disorders. Hypertensive emergencies occur when severely elevated or sudden marked increase in blood pressure is associated with acute end-organ damage.

The key pathophysiological process is intense peripheral vasoconstriction, resulting in a rapid rise in blood pressure and a vicious circle of events, including ischaemia of the brain and peripheral organs.

Hypertensive urgencies

Malignant phase hypertension is a rare condition (1–3 per 100 000 per year, more common in black people) characterized by very high blood pressure, with bilateral retinal haemorrhages and/or exudates or cotton wool spots, with or without papilloedema.

Presentation is typically with visual disturbance, with or without headaches. Urinalysis may demonstrate proteinuria and haematuria, even in the absence of primary renal disease. Some patients with mild renal impairment at first presentation may improve, or even regain normal renal function, but this is unlikely to occur in those with more severe renal impairment at presentation.

Patients with severe hypertension who are asymptomatic require controlled reduction in blood pressure with oral antihypertensive agents. Over-rapid blood pressure reduction may be hazardous, leading on occasion to ischaemic complications such as stroke, myocardial infarction, or blindness. The maximum initial fall in blood pressure should not exceed 25% of the presenting value, with the initial aim of treatment being to lower the diastolic pressure to about 100 to 105 mm Hg over a period of 2 to 3 days. The first-line oral antihypertensive agent is either a short-acting calcium antagonist (such as nifedipine, 10–20 mg of the tablet formulation: sublingual or capsular preparations should never be used) or a β‎-blocker (such as atenolol, 25 mg initial dose).

Hypertensive emergencies

Patients who are symptomatic with acute life-threatening complications of severe hypertension, such as hypertensive encephalopathy, hypertensive left ventricular failure, or aortic dissection, require parenteral antihypertensive therapy to promptly reduce the blood pressure in a carefully controlled manner. Blood pressure should be reduced by 25% over several hours, depending on the clinical situation, usually with a target diastolic blood pressure of less than 100 to 110 mm Hg. The first-line treatment for most hypertensive emergencies is either intravenous sodium nitroprusside or intravenous labetalol, with β‎-blockade essential in patients with aortic dissection.

Hypertensive emergencies and urgencies carry a poor short-and long-term prognosis unless adequately managed. Initial over-rapid reduction of blood pressure to a normal value is dangerous, but—in the long term—blood pressure should eventually be reduced to accepted blood pressure targets.


Hypertensive emergencies occur when severe hypertension is associated with acute end-organ damage. These can take a variety of forms and can occur at any age. They may be acute life-threatening medical conditions, and are associated with either severe hypertension or sudden marked increases in blood pressure (Box Symptomatic patients with complications such as aortic dissection and hypertensive encephalopathy require parenteral antihypertensive therapy to reduce the blood pressure promptly, but in a controlled manner and with careful monitoring because over-rapid treatment may in itself be hazardous, leading, on occasions, to ischaemic complications such as stroke, myocardial infarction, or blindness. Thus, in patients who have severe hypertension but are asymptomatic, slower, controlled, reduction in blood pressure should be achieved with oral antihypertensive agents, making such situations hypertensive ‘urgencies’ rather than ‘emergencies’.

LSD, lysergic acid diethylamide; MDMA, 3,4-methylenedioxymethamphetamine.

In general, there has been a decline in the incidence of hypertensive emergencies over the past 20 years in the Western world, which may possibly be the result of the more effective detection, diagnosis, and treatment of mild to moderate hypertension.

If patients with hypertensive emergencies are not recognized or treated appropriately, the mortality and morbidity can be very high, with the 1-year mortality being 70–90%, and the 5-year mortality 100%. With adequate blood pressure control, the 1-year and 5-year mortality rates decrease to 25 and 50%, respectively.

Hypertensive emergencies occur most commonly in patients with previous hypertension, especially if inadequately managed. Nevertheless, some patients can present with hypertensive emergencies de novo, without any previous history of hypertension.

Very severe and malignant hypertension are more likely to be associated with underlying causes such as renovascular disease, primary renal diseases, phaeochromocytoma, and connective tissue disorders, but malignant hypertension complicating primary hyperaldosteronism (Conn’s syndrome) is very rare. About 40% of patients with malignant hypertension have an underlying cause.


The common denominator in hypertensive emergencies is intense peripheral vasoconstriction, resulting in a rapid rise in blood pressure and a vicious circle of events, including ischaemia of the brain and peripheral organs. This ischaemia stimulates neurohormone and cytokine release, exacerbating vasoconstriction and ischaemia, further increasing blood pressure, and resulting in target organ damage. Renal ischaemia also leads to activation of the renin–angiotensin system (Fig., causing further rise in blood pressure and microvascular damage with excessive endothelial injury. Myointimal proliferation in the vasculature may further exacerbate the situation, resulting in an intravascular prothrombotic state disbalance (agglutination/ coagulation) and the development of thrombotic microangiopathies characterized by thrombocytopenia and microangiopathic haemolytic anaemia (anaemia accompanied by elevated serum lactate dehydrogenase and the presence of schistocytes in the peripheral blood smear), causing further microvascular dysfunction and organ ischaemia.

Fig. Main potential mechanisms and target organ involvement in the diagnosis of malignant hypertension. LVH, left ventricular hypertrophy.

Fig. Main potential mechanisms and target organ involvement in the diagnosis of malignant hypertension. LVH, left ventricular hypertrophy.

Modified from Shantsila A, Lip GYH (2017). Malignant Hypertension Revisited— Does This Still Exist? Am J Hypertens, 30, 543–9.

With mild to moderate elevation of blood pressure, the initial response of the vasculature is arterial and arteriolar vasoconstriction— such autoregulation maintaining tissue perfusion at a relatively constant level and preventing the raised blood pressure from damaging smaller, more distal blood vessels. Later, arteriolar hypertrophy also minimizes the transmission of pressure to the capillary circulation. In normotensive subjects, the upper limit of autoregulation can be a mean arterial pressure of 120 mm Hg (equivalent to 160/100 mm Hg), but in chronic hypertension, where the vessels are hypertrophied by long-standing hypertension, the lower limit of autoregulation of cerebral blood flow is shifted towards higher blood pressures (Fig., with impairment of the tolerance to acute hypotension. However, the process of autoregulation fails with rapid and severe rises in blood pressure, leading to a rise in pressure in the arterioles and capillaries, causing vascular damage. Disruption of the endothelium allows plasma constituents (including fibrinoid material) to enter the vessel wall, narrowing or obliterating the lumen in many tissue beds, the level at which fibrinoid necrosis occurs depending upon the baseline blood pressure. In the cerebral circulation, this can lead to the development of cerebral oedema and the clinical picture of hypertensive encephalopathy.

Fig. Autoregulation of myocardial and cerebral blood flow in normotensive and hypertensive patients.

Fig. Autoregulation of myocardial and cerebral blood flow in normotensive and hypertensive patients.

Reprinted from The Lancet, Vol. 330, Strandgaard S and Haunsø S, Why does antihypertensive treatment prevent stroke but not myocardial infarction?, pp. 658–60. Copyright (1987), with permission from Elsevier.

In addition to protecting the tissues against the effects of hypertension, autoregulation maintains perfusion during the treatment of hypertension via arterial and arteriolar vasodilatation. However, falls in blood pressure below the autoregulatory range can lead to organ ischaemia, and the arteriolar hypertrophy induced by chronic hypertension means that target organ ischaemia will occur at a higher pressure than in previously normotensive subjects.

Malignant hypertension, a hypertensive ‘urgency’

The malignant phase of hypertension is a rare condition characterized by very high blood pressure, with bilateral retinal haemorrhages and/or exudates or cotton wool spots, with or without papilloedema (Fig. Its pathophysiological definition is based on the histological hallmark of fibrinoid necrosis of arterioles in many tissues, particularly the kidney—changes which are broadly similar to those seen in the haemolytic–uraemic syndrome or scleroderma. Mucoid intimal proliferation in renal interlobular arteries and ischaemic collapse of the glomerular tufts may also be seen. Myointimal hyperplasia is a common finding in black patients, with the consequent intrarenal vascular disease leading to ischaemia of the juxtaglomerular apparatus and activation of the renin–angiotensin system with further vasoconstriction and wall damage, as well as exacerbation of hypertension.

Fig. Ocular fundus in hypertension, showing papilloedema, exudates, and a few haemorrhages.

Fig. Ocular fundus in hypertension, showing papilloedema, exudates, and a few haemorrhages.


Malignant hypertension may be becoming rarer in some countries, particularly among white populations, but it still remains a common problem in developing countries and in other populations with health and social deprivation, where it is an important cause of end-stage renal failure. In west Birmingham in the United Kingdom, the incidence of malignant hypertension is around 1 to 2 per 100 000 population per year, with no clear reduction between 1970 and 2011 in the number of new cases seen, the mean duration of known hypertension before presentation, presenting blood pressures, or the number of antihypertensive drugs that were being used. These data are reinforced by an analysis from Amsterdam of 122 patients with malignant hypertension in a multiethnic population, where the incidence rate was approximately 2.6 per 100 000 per year, and higher among blacks, approximately 7.3 per 100 000 of population per year. Increasing hospital admissions of patients with either malignant hypertension or hypertensive encephalopathy has been observed in retrospective analysis of US data since 2007. These observations may reflect increasing diagnosis of malignant hypertension with encephalopathy, but at the very least there is no evidence of decline in the incidence of malignant hypertension.

Although essential hypertension is usually the most common underlying cause of malignant hypertension in adults, secondary causes (especially renal disease) are more prevalent among younger patients, being identified in up to 40% of white and 10% of black subjects. In children (aged <16 years) with malignant hypertension, parenchymal renal disease is the commonest cause (63%), with 33% having renovascular hypertension (aortoarteritis and fibromuscular dysplasia), and only 5% with essential hypertension.

There is an unexplained association between cigarette smoking and the use of oral contraceptive pill and the development of malignant hypertension, that remains unexplained. Very rarely, the oral contraceptive pill may be implicated, consistent with the well-recognized increase in blood pressure in some women taking the combined oestrogen/progesterone oral contraceptive pill. It is uncertain whether oral contraceptives cause malignant hypertension directly, or whether they simply exaggerate a pre-existing tendency to raised blood pressure.

Malignant hypertension can occur in older people, and is more common in Afro-Caribbean than in white and Indo-Asian populations. Possible reasons for this include the relative resistance of black patients to some antihypertensive therapies and, perhaps, poorer drug compliance. In many series, black individuals had higher systolic blood pressures and more renal dysfunction than whites.

One reason for the failure of malignant hypertension to decline in some centres may be inadequate medical screening facilities among poorly educated people with a limited understanding of the nature of the disease and the need to comply with antihypertensive therapy. Any reported tendency towards reduction in the incidence of malignant hypertension may be because increasing use of drug therapy in milder grades of hypertension prevents progression to the malignant phase.


The diagnosis of malignant hypertension is usually based on the association of severely elevated blood pressure with a Keith and Wagener stage III or IV retinopathy. More recently, it has been suggested to consider that malignant hypertension with retinopathy is only one of several possible presentation(s) of acute hypertension with multiorgan damage (MOD). The presence of disturbance of at least three different target organs (kidney, heart, brain or microangiopathy) in association with acute blood pressure elevation is described as ‘hypertension MOD’, which would need to be managed as a hypertensive emergency, even though retinopathy is lacking.

Clinical features

The predominant presenting symptom is visual disturbances, accompanied in some cases by headaches. Unfortunately, some patients with malignant hypertension remain asymptomatic, and others present at a late stage of their disease, this proportion ranging from 10% to 75% in one series from Nigeria.

In the west Birmingham series, the presenting mean systolic and diastolic blood pressures have remained surprisingly similar over the 50 years surveyed (average blood pressure 229/142 mm Hg), despite improvements in antihypertensive therapy. Heart failure, angina, or myocardial infarction are complicating features in approximately 20% of patients. The ECG shows that many patients have left ventricular hypertrophy, and many have cardiomegaly on chest radiography. However, some patients do have normal chest radiographs, ECGs, or echocardiograms despite very high blood pressure, suggesting that hypertension may have been of recent onset. The proportion of de novo diagnoses of malignant hypertension ranges from 55% to 60% in different registries.


All patients with malignant hypertension need a detailed clinical history and examination, and investigation with blood tests (full blood count, serum biochemistry including electrolytes and renal function), 12-lead ECG, chest radiography, and urinalysis. Fundoscopy and retinal photography are mandatory. Urinalysis may demonstrate proteinuria and haematuria, even in the absence of primary renal disease, but the presence of proteinuria is a poor prognostic sign. The kidneys should be imaged by abdominal ultrasonography to assess renal size and appearance, with a low threshold for proceeding to renal angiography to look for renal artery stenosis if the kidneys are asymmetric. In all patients a 24-h urine collection is necessary for catecholamines (see Chapter 16.17.3), and urinary protein excretion should be estimated (most readily by measurement of urinary albumin/creatinine ratio, ACR). These initial screening tests serve to identify patients in whom additional investigations may be appropriate to detect an underlying cause of hypertension.

The full blood count and film may reveal the anaemia of chronic renal failure or occasionally a thrombotic microangiopathy, with thrombocytopenia and microangiopathic haemolytic anaemia—with red cell fragmentation and intravascular haemolysis—possibly related to the degree of arteriolar fibrinoid necrosis, excessive endothelial injury, along with activation of the renin-angiotensin-aldosterone system and an intravascular prothrombotic state. The presence of thrombotic microangiopathy is associated with worse recovery of renal function in the long term.

Serum urea and creatinine should initially be measured daily: renal impairment may have significant prognostic implications. Mild hypokalaemia due to secondary hyperaldosteronism may be present, which usually resolves after control of the hypertension. Only very rarely does hypokalaemia indicate primary hyperaldosteronism (Conn’s syndrome), but if it is extreme or persists despite good blood pressure control, then the characteristic findings of low renin levels, but high aldosterone concentrations, may be present. More commonly, both plasma renin and aldosterone levels are high in malignant hypertension, usually attributed to juxtaglomerular ischaemia. The inflammatory markers erythrocyte sedimentation rate and C-reactive protein are often modestly elevated in malignant hypertension, but measurement of autoantibodies (antinuclear antibodies and antineutrophil cytoplasmic antibodies) can be used to discern uncommon cases due to vasculitis. Renal biopsy is required to make a specific diagnosis in some instances, but should not be performed until blood pressure is controlled.

The chest radiograph may show cardiomegaly and the presence of pulmonary oedema. In a recent series of patients with malignant hypertension undergoing echocardiography, features included left ventricular hypertrophy, impaired systolic and diastolic function, and a dilated left atrium, were evident. Systolic impairment, measured by global longitudinal strain, improved significantly as early as 2 months after initiation of treatment and was usually restored completely at 1-year follow-up. Long-term treatment with good blood pressure control results in regression of the left ventricular hypertrophy and improvement of diastolic dysfunction on tissue Doppler, although typically incomplete. These structural/functional abnormalities may predispose patients to cardiovascular complications including heart failure and cardiac arrhythmias, such as atrial fibrillation.

Hypertension and atrial fibrillation commonly coexist, and both are additive to the risk of stroke. In particular, the presence of uncontrolled hypertension increases the risk of stroke and thromboembolism associated with this common arrhythmia. Atrial fibrillation can be regarded as another manifestation of hypertensive target organ damage.



As described earlier and in Chapter 16.17.2, the most widely used classification of hypertensive changes in the fundus is that of Keith, Wagener, and Barker—the strength of this being the correlation in the original description between clinical findings and prognosis (Table However, this classification has now been made obsolete by advances in the understanding of the pathophysiology of arterial hypertension and the availability of effective antihypertensive therapy. Ophthalmoscopic grading of the retinal changes in hypertension has been simplified into mild, moderate, and severe levels (see Chapter 16.17.2), and can be further reduced into two groups: grade A (nonmalignant)—arteriolar narrowing and focal constriction, which also correlate with age and general cardiovascular status as well as blood pressure; and grade B (malignant)—linear flame-shaped haemorrhages, and/or exudates, and/or cotton wool spots, with or without disc swelling. Papilloedema is an unreliable physical sign, and its presence or absence in the context of other grade B changes does not indicate a worse prognosis.

Table The Keith, Wagener, and Barker classification of hypertensive retinopathy

Grade 1

Grade 2

Grade 3

Grade 4

Retinal findings

Mild narrowing or sclerosis of the retinal arterioles

Moderate to marked sclerosis of the retinal arterioles

Retinal oedema, cotton wool spots, and haemorrhages

All the above and optic disc oedema

Exaggerated arterial light reflex

Sclerosis and spastic lesions of retinal arterioles

Venous compression at arteriovenous crossings (‘nipping’)

Macular star

Percentage surviving in original series

1 year





3 years





5 years





Grades 1 and 2 are broadly similar and are related to age and general cardiovascular status as well as blood pressure. Grades 3 and 4 are much more alike and both are now considered to be ‘malignant’. See Chapter 16.17.2 for further discussion.

Similar retinal appearances with haemorrhages and papilloedema can occur in severe anaemia, connective tissue disease, and infective endocarditis. Idiopathic intracranial hypertension with bilateral papilloedema is itself associated with hypertension and obesity but this is not indicative of hypertension entering its malignant phase. Nevertheless, severe hypertension and lone bilateral papilloedema may be a variant of malignant hypertension, with similar clinical features and prognosis. The retinal features of malignant hypertension regress over a period of 2 to 3 months if good blood pressure control is achieved. There is an association between the degrees and dynamic of the retinal and renal function changes, thus emphasizing the fact that patients with malignant hypertension develop systemic microvascular damage/dysfunction involving several organs.

Renal involvement

Renal involvement in malignant hypertension has been referred to as malignant nephrosclerosis, manifest as haematuria, proteinuria, and (sometimes) acute renal failure. Renal failure is the commonest cause of death, with presenting urea and creatinine levels independent predictors of survival.

When antihypertensive therapy is initiated and blood pressure control achieved, the effect on renal function is variable. In the short term, renal function stabilizes in 10% of cases, deteriorates progressively in 30%, and deteriorates transiently before improving over a matter of weeks in the remainder. Renal failure is more frequent (two-to threefold) in black, than in white, individuals (Fig., but mainly because of higher serum creatinine levels at presentation.

Fig. Proportion with renal failure after presentation with malignant hypertension, stratified for ethnicity.

Fig. Proportion with renal failure after presentation with malignant hypertension, stratified for ethnicity.

From Van den Born BJ, et al. (2006). Ethnic disparities in the incidence, presentation and complications of malignant hypertension. J Hypertens, 24, 2299–304.

Isles and coworkers have suggested that the renal outcome of patients with malignant hypertension can be considered in three groups, each with a different renal prognosis: (1) patients whose serum creatinine is less than 300 µmol/litre at presentation, who do well with effective antihypertensive therapy; (2) patients with chronic renal failure (serum creatinine >300 µmol/litre) who do not require renal dialysis immediately, but are unlikely to maintain or recover renal function, except possibly in the short term, and commonly progress to end-stage renal failure; and (3) a small group with acute renal failure. It is possible that some of these patients may have poststreptococcal acute nephritic syndrome, characterized by retinopathy, fluid retention, and usually complete renal recovery.

In the west Birmingham series, Lip et al. did not find such a clear distinction based on serum creatinine and found that renal function continued to deteriorate among many patients with malignant hypertension, despite good blood pressure control at follow-up. About half of the patients with severe renal impairment at presentation demonstrated either static or improved renal function, and there was no evidence that those cases where renal function remained static were those with less renal impairment at presentation. The severity of malignant hypertension at presentation did not predict outcome, but the quality of control of systolic blood pressure at follow-up and the height of the serum creatinine at presentation did, suggesting that careful monitoring of renal function and aggressive treatment of blood pressure is mandatory in patients with this condition. End-stage renal disease remains a significant cause of death in patients with malignant hypertension.

High serum urate levels are associated with greater renal impairment at baseline, as well as higher diastolic blood pressures, but are not predictive of deterioration in renal function or overall survival in patients with malignant hypertension.

There are varying reports of the frequency of renovascular disease in malignant hypertension, which may be due to the frequency with which renal angiography is performed. In older patients, renal artery stenosis is likely to be due to atheromatous disease, which itself may be a consequence of chronic hypertension and chronic hyperlipidaemia, as well as cigarette smoking. In younger patients, and particularly in women, renal artery stenosis may be due to fibromuscular dysplasia of the renal arteries, with the characteristic ‘string of beads’ appearance on renal angiography. The value of surgical or angioplastic correction of atheromatous disease is debatable, possibly producing no better results than effective blood pressure control with antihypertensive drugs. In patients with fibromuscular dysplasia, however, renal angioplasty with stenting is worthwhile and will often lead to a normal blood pressure level.


All patients with malignant hypertension require assessment, investigation, and commencement of therapy under supervision, preferably as an in-patient. Blood pressure should be measured 4-hourly, with the initial aim of treatment being to lower the diastolic pressure near about 100–105 mm Hg over a period of 2 to 3 days, with oral therapy and dose escalation at daily intervals, if necessary. The maximum initial fall in blood pressure should not exceed 25% of the presenting value, gradual reduction allowing adaptation of disordered tissue autoregulation and avoidance of target organ ischaemia. More aggressive antihypertensive therapy is both unnecessary and dangerous, as it may reduce the blood pressure to below the autoregulatory range, leading to ischaemic events such as strokes, heart attack, or renal failure.

The first-line oral antihypertensive agent is either a short-acting calcium antagonist (such as nifedipine) or a β‎-blocker (such as atenolol). An appropriate dose of nifedipine is 10–20 mg of the tablet formulation, which can be repeated or increased, as necessary, to bring about gradual reduction in blood pressure. Nifedipine is not absorbed from the oral mucosa, and there have been reports of complications including visual loss, cerebral infarction, and myocardial infarction with nifedipine therapy using the short-acting sublingual capsules, which produce unpredictable falls in blood pressure and should never be used. β‎-Blockers are useful alternatives, but should be avoided in patients with asthma or where there is a high suspicion of an underlying phaeochromocytoma. It is sensible to start with small doses, such as 25 mg of atenolol, increasing the dose as necessary. The combination of oral atenolol and nifedipine is often a well-tolerated and effective regime.

Diuretics should be restricted to those with evidence of fluid overload. Some patients are volume depleted, presumably secondary to a pressure-related diuresis and activation of the renin–angiotensin system. Captopril and the other angiotensin converting enzyme (ACE) inhibitors can produce rapid and dangerous falls in blood pressure, particularly in patients with hypokalaemic secondary hyperaldosteronism and hyponatraemia secondary to juxtaglomerular ischaemia or renovascular disease, which may be unrecognized in the acute situation.

Over a period of about 1 to 2 weeks, further antihypertensive drugs should be added in to achieve a gradual reduction of blood pressure to less than 140/85 mm Hg. Triple or quadruple drug regimens are invariably necessary in the long term.

Drugs for the treatment of hypertensive emergencies and urgencies are summarized in Tables and

Table Oral drugs for hypertensive emergencies and urgencies





Atenolol (25–50 mg)

Safe unless contraindicated

Calcium channel blockers

Nifedipine capsules


Nifedipine tablets (10–20 mg)



Onset of action is slow (c.5 days)


Useful if tachycardia or associated supraventricular arrhythmia


Not better than nifedipine by mouth



Little experience


Little experience





Slow onset

Loop diuretics

Only if heart failure

ACE inhibitors

Captopril (6.25–50 mg, three times a day)

If patient on diuretic, or if renal artery stenosis is undiagnosed, may cause rapid falls in blood pressure and acute renal failure

Table Parenteral drugs for the treatment of hypertensive emergencies



Use and adverse effects


Sodium nitroprusside

Dilates both arterioles and veins via generation of cGMP which then activates calcium-sensitive potassium channels in the cell membrane

IV infusion; rapid onset and offset of action, minimizing the risk of hypotension

Recommended starting dose is 0.25–0.5 μ‎g/kg per min, increased as necessary to a maximum dose of 8–10 μ‎g/kg per min, for up to 10 min

Nitroprusside should not be given to pregnant women

Can cause intrapulmonary shunting and coronary ‘steal’

Thiocyanate and cyanide toxicity manifest by clinical deterioration, muscle twitching, altered mental status, and lactic acidosis, and can be fatal

The most effective parenteral drug for most hypertensive emergencies

Easy to control on a minute-to-minute basis

Glyceryl trinitrate (nitroglycerin)

Similar action to nitroprusside, but greater venodilatation

IV infusion, 5–100 μ‎g/min

Onset of action is 2–5 min, duration of action 5–10 min

Headache (due to direct vasodilatation) and tachycardia (reflex sympathetic activation)



Most useful in patients with symptomatic coronary disease and in those with hypertension following surgery


Combined β‎-and α‎-blocker

Rapid onset of action (5 min or less) Bolus of 20 mg initially, followed by 20–80 mg every 10 min to a total dose of 300 mg

The infusion rate is 0.5–2 mg/min

Avoid in patients with contraindications to β‎-blockers

Safe in patients with active coronary disease since it does not increase the heart rate

Also useful in the perioperative care of patients with severe hypertension



Rapid onset and offset of action IV

infusion, titrated to heart rate and blood pressure response

Reduces myocardial ischaemia

Avoid in patients with contraindications to β‎-blockers

Useful in tachycardias, hyperdynamic heart, arrhythmias (e.g. atrial fibrillation), perioperative hypertension, aortic dissection


Dihydropyridine calcium channel blocker

IV infusion at 5–15 mg/h

Headache and flushing


Becoming more popular

Useful for most hypertensive emergencies, except acute heart failure


Arteriolar vasodilator that has little effect on the venous circulation

IV bolus 50–150 mg or infusion 2–10 mg/h

Peak effect seen within 15 min, lasts for 4–24 h

Do not use in patients with angina pectoris, myocardial infarction, pulmonary oedema, or a dissecting aortic aneurysm

Can cause marked fluid retention and a diuretic may be needed

Give β‎-blocker to block reflex activation of the sympathetic nervous system

Rarely used nowadays as may cause excessive blood pressure reduction which is difficult to reverse


Direct arteriolar vasodilator

IV bolus

Initial dose is 10–20 mg

Fall in blood pressure begins within 10–30 min and lasts 2–4 h

Tachycardia, flushing, headache, vomiting

Aggravation of angina

Hypotensive response to hydralazine is less predictable

Used in pregnant women


α‎-Adrenergic blocker

IV bolus, 5–10 mg every 5–15 min as necessary

Severe hypertension due to phaeochromocytoma and other syndromes of increased catecholamine activity, such as drug abuse, MAO-induced hypertension, and so on

Tachyphylaxis means that doses need to be escalated

IV, intravenous; MAO, monoamine oxidase.


Historically, when malignant hypertension was left untreated, around 80% of patients died within 2 years, hence the name. In west Birmingham, between 1965 and 2006, after a median follow-up of 103 months (range 1–539 months), 40% were alive and not requiring renal replacement therapy, 3.2% were on long-term haemodialysis, and 40% were dead, with the remainder lost to follow-up. The commonest causes of death were renal failure (39.7%), stroke (23.8%), myocardial infarction (11.1%), and heart failure (10.3%).

The advent of effective and tolerable antihypertensive drug therapy has improved prognosis. For example, in the west Birmingham series, 5-year mortality rates reduced from 76% prior to 1967 to 7% for the years 1997 to 2011 (Fig. The series by Scarpelli and coworkers reported a 12-year survival rate of about 69%, although patients with malignant hypertension diagnosed after 1980 had a 100% survival rate. More contemporaneous data from the Amsterdam series, describing patient incidents between 1993 and 2005, showed that 10% had died and 19% needed renal replacement therapy after a mean follow-up of 4 years. Hence, whatever the cause of malignant hypertension, progressive renal impairment is still a common complicating factor, with many patients needing dialysis in the long term.

Fig. Rates of 5-year mortality in patients with malignant hypertension diagnosed in different time periods.

Fig. Rates of 5-year mortality in patients with malignant hypertension diagnosed in different time periods.

From Shantsila A, Shantsila E, Beevers DG, Lip GYH (2017). Predictors of 5-year outcomes in malignant phase hypertension: the West Birmingham Malignant Hypertension Registry. J Hypertens, 35, 2310–14.

The importance of early diagnosis is emphasized as patients tend to develop clinical symptoms only at a late stage of their disease. Black men with malignant hypertension have a poor prognosis when compared with other ethnic groups or women; they also present with more severe hypertension and greater renal damage, which are independent predictors of outcome and explain the poorer prognosis.

Hypertensive emergencies

Hypertensive left ventricular failure

Hypertension causes heart failure by a number of mechanisms: these include pressure overload on the heart due to the raised peripheral vascular resistance, reduced left ventricular compliance (e.g. in left ventricular hypertrophy), an increased risk for coronary artery disease and the precipitation of cardiac arrhythmias (such as atrial fibrillation). Severe hypertension results in a significant increase in afterload and may result in decompensation of the failing heart.

In very severe hypertension with marked pulmonary oedema, intravenous sodium nitroprusside may be necessary to reduce preload and afterload in addition to conventional management with opioids and loop diuretics. However, metabolism of nitroprusside to cyanide, possibly leading to the development of cyanide or (rarely) thiocyanate toxicity, may be a limitation. This manifests with altered mental status and lactic acidosis, and can be fatal. The risk of toxicity is increased in children, also with prolonged treatment (>24–48 h), underlying renal insufficiency, and requirement for high doses (>2 µg/kg per min). An infusion of sodium thiosulfate can be used in affected patients to provide a sulfur donor to detoxify cyanide into thiocyanate.

Nitrates may also be used to treat hypertensive left ventricular failure, but they are less potent than sodium nitroprusside. ACE inhibitors should be considered only after the patient’s condition is stabilized, when they are well established to be life-saving in those with left ventricular systolic impairment, lead to long-term regression of left ventricular hypertrophy, and may also improve heart failure secondary to diastolic dysfunction.

Hypertensive encephalopathy

Hypertensive encephalopathy refers to the presence of signs of cerebral oedema caused by breakthrough hyperperfusion following severe and sudden rises in blood pressure. There is failure of autoregulatory vasoconstriction with focal or generalized dilatation of small arteries and arterioles and impaired macro-and microvascular function. This leads to high cerebral blood flow, dysfunction of the blood–brain barrier, and the formation of brain oedema, which is thought to cause the clinical symptoms. The condition is now very rare, although recent retrospective analysis of the US data showed an increasing trend for the hospital admission of patients with either hypertensive encephalopathy or malignant hypertension after 2007. These observations could reflect improved recognition and diagnosis of malignant hypertension with encephalopathy, as admissions for essential hypertension fall. It is essential to perform a CT or an MRI scan to ensure that this hypertensive emergency is distinguished from other neurological syndromes associated with high blood pressure, including intracerebral or subarachnoid haemorrhage, ischaemic stroke, or lacunar infarction.

Hypertensive encephalopathy is usually associated with a history of hypertension that has been inadequately treated, or where previous treatment has been discontinued. It is characterized by the insidious onset of headache, nausea, and vomiting, followed by visual disturbances, field loss, and fluctuating, nonlocalizing neurological symptoms such as restlessness, confusion, and—if the hypertension is not treated—seizures and coma. Severe retinopathy is frequently, but not always, present.

CT or MRI may demonstrate white matter oedema, with the resolution of changes after patient stabilization. One of these tests is mandatory to exclude cerebral haemorrhage or infarction. Indeed, the increased use of CT scanning has demonstrated that almost all patients who appear to have hypertensive encephalopathy have cerebral infarction or haemorrhage with surrounding oedema and space-occupying cerebral symptoms. Lumbar puncture is not indicated in the management of patients with malignant hypertension; but if obtained (perhaps in ignorance of the diagnosis) the cerebrospinal fluid is usually normal, although at an increased pressure. The ECG may show variable transient, focal, or bilateral abnormalities.

Sodium nitroprusside is the drug of choice for genuine hypertensive encephalopathy, but is not usually given if there is a cerebral infarct or haemorrhage. Parenteral labetalol and nitrates have also been used successfully. Rarely, diazoxide and hydralazine have been given, but they can cause precipitate and life-threatening acute falls in blood pressure, and they require concurrent β‎-blocker administration to minimize reflex sympathetic stimulation. Sublingual nifedipine capsules should never be used (see ‘Management’, earlier). Phentolamine is used only in patients with severe hypertension due to increased catecholamine activity, such as that seen in phaeochromocytoma, or after tyramine ingestion in a patient being treated with a monoamine oxidase inhibitor. ACE inhibitors are best avoided in the early stage as they may, even in a very low dose, cause precipitate falls in blood pressure and life-threatening reduction in cerebral perfusion, particularly when patients are fluid depleted due to diuretic therapy or in the presence of renal artery stenosis.

Severe pre-eclampsia and eclampsia are discussed in detail elsewhere (see Chapter 14.4). They may present with clinical features similar to hypertensive encephalopathy, and treatment is broadly similar, with labetalol infusions, magnesium sulphate, and early delivery of the fetus.

Hypertension with unstable angina or acute myocardial infarction

In a patient presenting with an acute coronary syndrome (unstable angina or acute myocardial infarction) and severe hypertension, a ‘true’ hypertensive emergency, such as aortic dissection, must first be ruled out. The risk of bleeding and stroke is significantly increased if anticoagulation with heparin, antiplatelet therapies (such as glycoprotein IIb/IIIa inhibitors), or thrombolytic therapy is administered.

The appropriate initial treatment of patients with severe hypertension (>180/110 mm Hg) and an acute coronary syndrome should include the initiation of intravenous nitrates, with intravenous labetalol, sodium nitroprusside, or nicardipine as alternatives. The reduction of blood pressure should not be too abrupt: as with malignant hypertension, a gradual reduction is recommended in an endeavour to avoid further myocardial or brain ischaemia. As stated previously, sublingual nifedipine—once considered as a first-line drug—should not be used in view of its negligible oral absorption and the unpredictable hypotensive effects from later gastric absorption.

Anticoagulation or thrombolytic therapy can be administered when the blood pressure is adequately controlled (<180/110 mm Hg). In many centres, revascularization with primary percutaneous coronary angioplasty is increasingly the initial management option for acute ST-segment elevation myocardial infarction (STEMI).

Hypertension with acute stroke and after a stroke

It is common to find modestly elevated blood pressure in patients admitted to hospital following an acute stroke. Cerebral autoregulation is commonly impaired in this context, with flow becoming pressure dependent, hence excessive antihypertensive treatment may serve to worsen the cerebral damage resulting from intracerebral infarction or haemorrhage, and stroke physicians are very wary about lowering the blood pressure.

There are few randomized controlled trials to inform the management of this common problem. Current consensus only recommends acute blood pressure lowering where there is associated acute end-organ damage—for example, cardiac (acute myocardial infarction, severe left ventricular failure) or vascular urgencies (aortic dissection), hypertensive encephalopathy, acute renal failure, concurrent anticoagulant therapy (thrombolysis, intravenous heparin, and so on), or persistent blood pressure elevation with a threshold greater than 200/120 mm Hg for ischaemic stroke and greater than 180/105 mm Hg for haemorrhagic stroke. In these cases, oral therapy with small doses of nifedipine or atenolol may be required. Parenteral treatment or sublingual nifedipine is always contraindicated. The calcium antagonist nimodipine has beneficial effects on cerebral vasospasm following subarachnoid haemorrhage, but these effects are not related to the small fall in blood pressure with this drug.

Severe hypertension after a stroke is a risk factor for further stokes, and long-term treatment is worthwhile. It is unclear whether the immediate treatment of mild hypertension is of benefit. The role of antihypertensive medication before, during, and after a stroke can, therefore, be summarized as follows:

  • Before a stroke, it is of benefit to have blood pressure reduced to below 140/85 mm Hg, as stroke prevention can be achieved.

  • During a stroke, it is detrimental to have hypertension treated aggressively, in view of the disordered cerebral autoregulation.

  • After a stroke, the epidemiological associations of hypertension with recurrent stroke have not been entirely consistent, with some studies showing no association or a J-shaped relationship.

In recent years, many studies have reported on the effects of antihypertensive drugs—predominantly ACE inhibitors or angiotensin receptor blockers—in the early post-stroke setting. The Heart Outcomes Prevention Evaluation (HOPE) study reported a subset of 1013 subjects with a previous history of stroke or transient ischaemic attack (TIA), where there was a nonsignificant 15% reduction in total stroke recurrence with ramipril. In the PROGRESS trial, 6105 normotensive and hypertensive patients with a history of ischaemic or haemorrhagic stroke or TIA were randomized to perindopril (± indapamide), which reduced recurrent stroke by 28% and major vascular events by 26% during 4 years of follow-up.

The Morbidity and Mortality after Stroke Eprosartan Study (MOSES) compared eprosartan (an angiotensin receptor blocker) to nitrendipine (a dihydropyridine calcium channel blocker) in hypertensive-stroke survivors and found a 21% risk reduction in the primary endpoint of all cardiovascular and cerebrovascular events and a 25% reduction in recurrent cerebrovascular events in the eprosartan-treated patients.

In the CATIS Randomized Clinical Trial, patients with acute ischaemic stroke (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 h after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). In this trial, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge.

Data from the large Safe Implementation of Thrombolysis in Stroke– International Stroke Thrombolysis Register (SITS-ISTR) of 11 080 patients showed a U-shaped relation of death and physical independency with post-thrombolysis systolic blood pressure, with blood pressure of 141–150 mm Hg associated with the most favourable outcomes.

The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial pilot (INTERACT1) (n = 404) and main INTERACT2 (n = 2839) studies compared intensive (target <140 mm Hg) or guideline-recommended (target <180 mm Hg) systolic blood pressure lowering treatment in patients with spontaneous intracranial haemorrhage (<6 h). These showed favourable outcome on physical independency for intensive BP control (odds ratio 1.13, 95% confidence interval 1.00–1.26; p = 0.042) over the early and later recovery periods.

Management of blood pressure in a patient with aortic dissection

The detailed presentation, diagnosis, and treatment of aortic dissection is discussed in Chapter 16.14.1. On suspicion of the diagnosis, whether or not surgery is indicated, all patients should be treated pharmacologically to reduce the systolic blood pressure to around 110 mm Hg and the heart rate to 60–70 beats/min, thus reducing the force of systolic ejection to reduce aortic shear stress and limit the size of the dissection. Labetalol is an effective agent, or alternatively, sodium nitroprusside in conjunction with a β‎-blocker may be used. Patients should ideally have haemodynamic monitoring with an arterial line in position. Diagnostic tests are then performed on an urgent basis to confirm the dissection, identifying whether the ascending aorta is involved, and defining any vascular abnormalities resulting from the dissection.


We acknowledge the contribution of D. Gareth Beevers to previous editions of this chapter.

Further reading

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Cremer A, et al. (2015). From malignant hypertension to hypertension-MOD: a modern definition for an old but still dangerous emergency. J Hum Hypertens, 30, 463–6.Find this resource:

Gudbrandsson T, et al. (1979). Malignant hypertension. Improving prognosis in a rare disease. Acta Med Scand, 206, 495–9.Find this resource:

Harvey JM, et al. (1992). Renal biopsy findings in hypertensive patients with proteinuria. Lancet, 340, 1435–6.Find this resource:

He J, et al. (2014). Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial. JAMA, 311, 479–89.Find this resource:

Isles CG, McLay A, Boulton Jones JM (1984). Recovery in malignant hypertension presenting as acute renal failure. Q J Med, 212, 439–52.Find this resource:

Jhetam D, et al. (1982). The malignant phase of essential hypertension in Johannesburg blacks. S Afr Med J, 61, 899–902.Find this resource:

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Keith NM, Wagener HP, Barker NW (1939). Some different types of essential hypertension: their course and prognosis. Am J Med Sci, 196, 332–43.Find this resource:

Kumar P, et al. (1996). Malignant hypertension in children in India. Nephrol Dial Trans, 11, 1261–6.Find this resource:

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Leishman AWD (1959). Hypertension—treated and untreated: a study of 400 cases. Br Med J, i, 1361–3.Find this resource:

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Lip GYH, et al. (1995). Severe hypertension and lone bilateral papilloedema: a variant of malignant phase hypertension. Blood Press, 4, 339–42.Find this resource:

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Lip GYH, Beevers M, Beevers DG (1997). Does renal function improve following diagnosis of malignant phase hypertension? J Hypertens, 15, 1309–15.Find this resource:

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