Clinical use
This overview is a quick reference to the intravenous antihypertensive drugs used in a hypertensive emergency. It summarises the mechanism of action, the onset, the duration of effect, the dosing, the adverse effects and the important precautions.
A hypertensive emergency is defined by a markedly raised blood pressure in combination with new or progressive acute target organ damage. Common manifestations are hypertensive encephalopathy, intracerebral haemorrhage, acute coronary syndrome, acute left ventricular failure with pulmonary oedema, acute aortic syndrome, acute kidney injury, microangiopathic haemolysis, and severe pre-eclampsia or eclampsia. The blood pressure is often at least 180/120 mmHg, but no absolute threshold defines the condition. A rapid rise in blood pressure can cause serious organ damage even at lower levels, particularly in pregnancy [1,2].
Malignant hypertension is not entirely synonymous with a hypertensive emergency. The term denotes severe hypertension with advanced hypertensive retinopathy, usually retinal haemorrhages, exudates, cotton wool spots or papilloedema. Intravenous treatment is required if there is concomitant acute life-threatening organ damage. Isolated malignant retinopathy without other acute organ damage can often be treated more cautiously with oral drugs under careful observation [3,4].
A markedly raised blood pressure without acute target organ damage should not normally be lowered rapidly with intravenous drugs. Such treatment has not been shown to improve the prognosis and can cause hypotension, acute kidney injury, myocardial ischaemia or cerebral hypoperfusion. Pain, anxiety, urinary retention, hypoxia, drug withdrawal and incorrect blood pressure measurement must be corrected before treatment is intensified [1,2].
The evidence that any particular intravenous drug improves mortality or long-term functional outcome is limited. A Cochrane review found insufficient randomised evidence to determine which agent is best. The choice is therefore governed chiefly by the target organ damage, the pharmacology of the drug, comorbidity, and the ability to titrate safely [5].
Availability in Sweden. Several of the drugs in this overview are not routinely marketed in Sweden and may require a named-patient licence, among them clevidipine, nicardipine, fenoldopam, enalaprilat, phentolamine and sodium nitroprusside. Availability may change. Check the local formulary, the licensing status, the concentration, the dilution instructions and the local protocol before prescribing.
Basic principles of treatment
The patient should be managed in an emergency department, an intensive care unit, a coronary care unit or another setting that allows frequent blood pressure measurement and continuous monitoring. An arterial line is often appropriate when very rapid or precise control is required, for example in acute aortic syndrome, marked neurological organ damage, or treatment with sodium nitroprusside.
In most hypertensive emergencies the following is aimed for:
- Lower the mean arterial pressure by no more than about 20 to 25 per cent during the first hour.
- Thereafter, if the patient is stable, lower the blood pressure towards about 160/100 to 110 mmHg over the following 2 to 6 hours.
- Once the target organ damage has stabilised, the blood pressure can be lowered cautiously further over the following 24 to 48 hours [3,4,6].
This is a general principle, not a universal target. Chronic hypertension shifts autoregulation in the brain and kidneys towards higher pressures. Too rapid a normalisation can therefore cause cerebral, coronary or renal ischaemia. Neurological status, urine output, creatinine, acid–base status and signs of myocardial ischaemia must be monitored during treatment [4,6].
Important exceptions
| Condition | Overall strategy | Common first choices |
|---|---|---|
| Acute aortic syndrome | Immediate rate control and rapid reduction of the systolic blood pressure towards 100 to 120 mmHg, if organ perfusion permits | Esmolol or labetalol first, then a vasodilator if needed |
| Hypertensive encephalopathy | Lower the mean arterial pressure by no more than 20 to 25 per cent during the first few hours | Nicardipine or labetalol |
| Intracerebral haemorrhage | At a systolic blood pressure of 150 to 220 mmHg, a target of around 140 mmHg is often reasonable. Avoid a routine target below 140 mmHg | Nicardipine, clevidipine or labetalol |
| Acute ischaemic stroke without reperfusion treatment | Usually refrain from acute lowering if the blood pressure is below 220/120 mmHg and there is no other organ damage requiring treatment | Nicardipine or labetalol if needed |
| Thrombolysis in ischaemic stroke | Below 185/110 mmHg before treatment, thereafter below 180/105 mmHg during the first 24 hours | Nicardipine, clevidipine or labetalol |
| Hypertensive pulmonary oedema | Rapid reduction of preload and afterload, together with respiratory support | Nitroglycerin, sometimes clevidipine or nitroprusside |
| Acute coronary syndrome | Relieve ischaemia and reduce afterload without lowering the diastolic pressure too far | Nitroglycerin, and with suitable haemodynamics also a beta blocker |
| Pre-eclampsia or eclampsia | Treat a persistent blood pressure of at least 160/110 mmHg promptly | Labetalol, hydralazine or oral nifedipine |
| Phaeochromocytoma crisis | Alpha blockade before pure beta blockade | Phentolamine, then beta blockade if needed |
| Sympathomimetic intoxication | Sedation and reduction of central sympathetic drive first | A benzodiazepine, then a nitrate, phentolamine or another vasodilator |
In intracerebral haemorrhage, more intensive lowering to around 140 mmHg has not clearly reduced mortality, but it may reduce haematoma expansion and give a small improvement in functional outcomes. Lowering to below 140 mmHg has, by contrast, not shown any additional benefit and has in some studies increased the risk of renal complications [7].
In acute ischaemic stroke without reperfusion treatment, early blood pressure lowering can worsen perfusion of the penumbra. A Cochrane review found no overall reduction in death or dependency from acute blood pressure lowering [8]. After successful thrombectomy the systolic blood pressure should usually be kept at no more than 180 mmHg, while aggressive lowering below 140 mmHg may worsen the functional outcome [7].
In subarachnoid haemorrhage the evidence for a specific blood pressure target is very weak. Treatment must be individualised in consultation with a neurosurgeon or a neurointerventionist, taking into account the risk of rebleeding, cerebral perfusion, and whether the aneurysm has been secured [9].
Rapid choice of drug
| Clinical situation | Suitable options | Avoid, or use with particular caution |
|---|---|---|
| Neurological emergency | Nicardipine, clevidipine, labetalol | Nitroglycerin and nitroprusside when the intracranial pressure is raised |
| Acute aortic syndrome | Esmolol or labetalol, then nicardipine, clevidipine or nitroprusside | A pure vasodilator before rate control |
| Pulmonary oedema or acute coronary syndrome | Nitroglycerin | Beta blockers in acute decompensated heart failure |
| Bradycardia or AV block | Nicardipine, clevidipine | Esmolol, labetalol, metoprolol, clonidine |
| Asthma or bronchospasm | Nicardipine, clevidipine | Labetalol and other beta blockers |
| Impaired renal function | Nicardipine, clevidipine, labetalol | Nitroprusside for more prolonged treatment |
| Pregnancy | Labetalol, hydralazine, oral nifedipine | Enalaprilat; nitroprusside if a safer alternative exists |
| Phaeochromocytoma crisis | Phentolamine | Pure beta blockade before alpha blockade |
| Cocaine or amfetamine | A benzodiazepine first, then a nitrate or phentolamine | Pure beta blockade in the acute phase |
| Severe aortic stenosis | Cautious individual titration | Clevidipine and other potent vasodilators can cause critical hypotension |
Calcium channel blockers
Clevidipine
Clevidipine is an ultra-short-acting dihydropyridine that mainly dilates arterioles. It reduces systemic vascular resistance and afterload with little direct effect on venous capacitance, conduction and myocardial contractility. The compound is rapidly hydrolysed by esterases in blood and tissue, independently of renal and hepatic function [10].
| Property | Clevidipine |
|---|---|
| Trade name | Cleviprex® |
| Suitable situations | Neurological hypertensive emergency, perioperative hypertension, renal failure, a need for very rapid titration |
| Onset | About 2 to 4 minutes |
| Duration of effect after stopping | About 5 to 15 minutes |
| Administration | Continuous intravenous infusion |
| Starting dose | 1 to 2 mg/hour |
| Titration | The dose can initially be doubled about every 90 seconds. As the blood pressure approaches the target, smaller dose steps are used, usually 1 to 2 mg/hour every 5 to 10 minutes |
| Usual maintenance dose | 4 to 6 mg/hour, though higher doses are often necessary |
| Highest dose studied | 32 mg/hour. Because of the lipid load, no more than 1,000 mL of emulsion per 24 hours is normally recommended, corresponding to a mean dose of 21 mg/hour over 24 hours |
| Common adverse effects | Headache, nausea, hypotension, reflex tachycardia |
| Other risks | Hypertriglyceridaemia, atrial fibrillation, possible worsening of heart failure |
| Contraindications | Allergy to soya or egg, marked disorder of lipid metabolism, severe aortic stenosis |
| Monitoring | Blood pressure and heart rate continuously. Take account of other lipid emulsion being given, for example parenteral nutrition or propofol |
VELOCITY studied patients with a systolic blood pressure above 180 mmHg. Around 90 per cent reached the individually determined target range within 30 minutes. In a small subgroup with moderate to severe renal impairment the median time to target was 8.5 minutes, with no sign of systematic overshoot [11].
ECLIPSE included patients with perioperative hypertension in cardiac surgery. Clevidipine kept the blood pressure within the predefined range better than nitroglycerin and nitroprusside and about as well as nicardipine. The study does not show that clevidipine is generally superior in all hypertensive emergencies, since the population consisted mainly of cardiac surgical patients [12].
Nicardipine
Nicardipine is a dihydropyridine that produces mainly arteriolar dilatation. The claim that nicardipine produces more venodilatation than arteriolar dilatation is incorrect. The drug reduces systemic vascular resistance and afterload and has a good effect in the cerebral and coronary vascular beds.
| Property | Nicardipine |
|---|---|
| Trade name | Cardene® |
| Suitable situations | Hypertensive encephalopathy, intracerebral haemorrhage, ischaemic stroke when lowering is indicated, acute kidney injury, perioperative hypertension |
| Onset | About 5 to 15 minutes |
| Duration of effect after stopping | Usually 30 minutes to 4 hours, sometimes longer after a prolonged infusion |
| Administration | Continuous intravenous infusion |
| Starting dose | 5 mg/hour |
| Titration | Increase by 2.5 mg/hour every 5 to 15 minutes |
| Maximum dose | 15 mg/hour |
| Adverse effects | Headache, flushing, nausea, peripheral oedema, hypotension and reflex tachycardia |
| Caution | Acute decompensated heart failure, severe aortic stenosis and ongoing myocardial ischaemia with tachycardia |
| Practical disadvantage | The effect wears off more slowly than that of clevidipine, which can leave residual hypotension after the infusion has been stopped |
In a randomised comparison, 91.4 per cent of the patients given nicardipine reached their predefined systolic target within 30 minutes, compared with 76.1 per cent on intermittent labetalol boluses. The difference may in part reflect the comparison of a continuous infusion with bolus treatment. The study was not powered for mortality or functional outcome, and many participants had suspected rather than verified target organ damage [13].
ACE inhibitors
Enalaprilat
Enalaprilat is the active metabolite of enalapril. Its effect depends on renin activity and intravascular volume and can therefore be markedly unpredictable in acute illness. The drug has a long duration of effect and is poorly suited to situations in which the blood pressure must be adjustable minute by minute.
| Property | Enalaprilat |
|---|---|
| Trade name | Vasotec IV® |
| Use | Rarely justified in a hypertensive emergency. It may be considered in selected cases with high renin activity when short-acting titratable alternatives are unavailable |
| Onset | About 15 minutes |
| Peak effect | Often after 1 to 4 hours |
| Duration of effect | About 6 to 12 hours, sometimes up to 24 hours |
| Dose | 1.25 mg intravenously over 5 minutes. It may be repeated every 6 hours. A lower starting dose, for example 0.625 mg, should be considered in hypovolaemia, concomitant diuretic treatment or renal failure |
| Adverse effects | Prolonged hypotension, hyperkalaemia, deterioration in renal function and angio-oedema |
| Contraindications | Pregnancy, previous ACE inhibitor-induced angio-oedema and bilateral renal artery stenosis |
| Avoid in | Acute kidney injury, hypovolaemia, hyperkalaemia, acute myocardial infarction with unstable haemodynamics, and situations in which rapid reversibility is required |
Activation of the renin–angiotensin system in malignant hypertension and pressure natriuresis can make the patient very sensitive to ACE inhibition. Short-acting, titratable agents are therefore normally safer in the initial phase [4,14].
Beta blockers
Esmolol
Esmolol is a relatively beta-1 selective beta blocker with a very short half-life. It is metabolised by esterases in erythrocytes and its effect is largely independent of renal and hepatic function. Full recovery from beta blockade usually occurs within 20 to 30 minutes of stopping the infusion [15].
| Property | Esmolol |
|---|---|
| Trade name | Brevibloc® |
| First-line indication | Acute aortic syndrome with tachycardia or high contractility |
| Other uses | Perioperative hypertension, supraventricular tachycardia and selected cases of acute myocardial ischaemia |
| Onset | About 1 to 2 minutes after a loading dose |
| Duration of effect after stopping | About 20 to 30 minutes |
| Loading dose | 500 micrograms/kg intravenously over 1 minute. With very fragile haemodynamics, an infusion without a loading dose may be more appropriate |
| Starting infusion | 50 micrograms/kg/minute |
| Titration | Increase stepwise, often to 100, 150 and 200 micrograms/kg/minute |
| Maximum dose | Usually 200 micrograms/kg/minute for blood pressure control. Doses up to 300 micrograms/kg/minute are used in some protocols |
| Adverse effects | Hypotension, bradycardia, AV block, nausea, bronchospasm and a reduced cardiac output |
| Contraindications | Cardiogenic shock, marked bradycardia, high-grade AV block without a pacemaker, and acute decompensated heart failure |
| Caution | Asthma, peripheral hypoperfusion and concomitant treatment with other negatively chronotropic drugs |
In acute aortic syndrome, rate control must normally be established before a pure vasodilator is added. Otherwise reflex tachycardia and increased left ventricular ejection force can increase the shear stress in the aortic wall [6].
Labetalol
Labetalol blocks beta-1, beta-2 and alpha-1 receptors. It lowers the blood pressure and the heart rate without the same degree of reflex tachycardia as a pure vasodilator. The effect after a bolus can persist for several hours, which makes the drug less finely controllable than esmolol.
| Property | Labetalol |
|---|---|
| Trade name | Trandate® |
| Suitable situations | Hypertensive encephalopathy, stroke, acute aortic syndrome, perioperative hypertension and severe hypertension in pregnancy |
| Onset | About 2 to 5 minutes |
| Peak effect | Usually after 5 to 15 minutes |
| Duration of effect | About 2 to 4 hours |
| Bolus regimen | 20 mg intravenously over 2 minutes. Thereafter 20 to 80 mg every 10 minutes according to response |
| Maximum cumulative dose | Usually 300 mg |
| Infusion regimen | 0.5 to 2 mg/minute |
| Adverse effects | Hypotension, bradycardia, AV block, nausea, dizziness, postural hypotension, scalp paraesthesiae and bronchospasm |
| Contraindications | Severe asthma or active bronchospasm, high-grade AV block, marked bradycardia, cardiogenic shock and acute decompensated heart failure |
| Caution | Hepatic impairment and peripheral vascular disease |
In phaeochromocytoma, adequate alpha blockade must be established before pure beta blockade. The alpha-blocking effect of labetalol is relatively weak compared with its beta blockade, and the drug must not be regarded as a safe substitute for adequate alpha blockade in a marked catecholamine crisis [16].
In cocaine- or amfetamine-induced sympathetic activation, benzodiazepines are first-line treatment. A nitrate or phentolamine can be added if the hypertension or coronary spasm persists. Pure beta blockade should be avoided in the acute phase, since it could theoretically enhance alpha receptor-mediated vasoconstriction [17].
Metoprolol
Metoprolol is a beta-1 selective beta blocker but is not a routine first-line agent in a hypertensive emergency. Its effect is longer-lasting and less easily controlled than that of esmolol.
| Property | Metoprolol |
|---|---|
| Trade names | Seloken®, Lopressor® |
| Appropriate use | Concomitant tachycardia or myocardial ischaemia when beta blockade is indicated and there is little need for second-by-second titration |
| Onset | About 5 to 20 minutes |
| Duration of effect | Several hours |
| Dose | 2.5 to 5 mg intravenously, slowly. It can be repeated at about 5-minute intervals to a total of 15 mg, depending on the indication and the local protocol |
| Adverse effects | Bradycardia, hypotension, AV block, bronchospasm and worsening heart failure |
| Avoid in | Acute pulmonary oedema, cardiogenic shock, marked bradycardia and high-grade AV block |
Metoprolol must not be used simply to treat a high blood pressure reading. In acute aortic syndrome, esmolol or labetalol are usually better documented and more practically controllable.
Dopamine agonists
Fenoldopam
Fenoldopam is a peripheral dopamine-1 receptor agonist. It produces arteriolar vasodilatation and increases renal blood flow, natriuresis and diuresis. Compared with nitroprusside it has no cyanide problem. No established renal protective effect on clinical endpoints has, however, been demonstrated [18].
| Property | Fenoldopam |
|---|---|
| Trade name | Corlopam® |
| Possible use | Hypertensive emergency, particularly with concomitant renal impairment, where the drug is available |
| Onset | About 5 minutes |
| Duration of effect after stopping | About 30 to 60 minutes |
| Starting dose | 0.1 micrograms/kg/minute |
| Titration | Increase by 0.05 to 0.1 micrograms/kg/minute at intervals of at least 15 minutes |
| Maximum dose | 1.6 micrograms/kg/minute |
| Adverse effects | Headache, flushing, tachycardia, nausea and hypokalaemia |
| Caution | Glaucoma or raised intraocular pressure, tachycardia and myocardial ischaemia |
| Comment | It can raise the intraocular pressure. Reflex tachycardia can limit its use in coronary disease |
Centrally acting alpha-2 agonists
Clonidine
Clonidine reduces central sympathetic tone by stimulating alpha-2 receptors. The drug can lower the blood pressure effectively but is not a routine first-line agent in a hypertensive emergency. Its effect is less predictable than that of a titratable infusion, and sedation can make neurological monitoring difficult.
| Property | Clonidine |
|---|---|
| Trade names | Catapresan®, Catapres® |
| Possible use | Selected situations with sympathetic activation, withdrawal, or where clonidine withdrawal has contributed to the hypertension |
| Administration | Intravenously, intramuscularly, orally or transdermally depending on the formulation |
| Intravenous dose | 150 micrograms diluted according to the product information and given slowly over 5 to 10 minutes |
| Oral dosing | Individual. Oral clonidine must not be used as rapid, repeated treatment to normalise an asymptomatic high blood pressure |
| Adverse effects | Sedation, dry mouth, confusion, hallucinations, hypotension, bradycardia, AV block and constipation |
| Contraindications | Marked bradycardia and significant conduction disturbance |
| Interactions | Alcohol and other sedatives potentiate CNS depression. Tricyclic antidepressants can reduce the antihypertensive effect |
| Withdrawal | Abrupt withdrawal can cause rebound hypertension. Taper when the clinical situation allows |
Clonidine may be unsuitable in suspected stroke, encephalopathy or any other situation in which repeated assessments of the level of consciousness are central. In renal failure the elimination may be prolonged, and the dose must therefore be individualised even though no simple standardised dose reduction is always specified.
Nitric oxide donors
Nitroglycerin
Nitroglycerin is converted to nitric oxide and increases cyclic GMP in vascular smooth muscle. Low doses produce mainly venodilatation and a reduced preload. Higher doses also produce arteriolar dilatation and a reduced afterload. The drug is particularly useful in hypertensive pulmonary oedema and acute coronary syndrome [19].
| Property | Nitroglycerin |
|---|---|
| Trade names | Glytrin®, Nitrolingual®, Suscard® and several intravenous preparations |
| First-line indications | Acute pulmonary oedema, acute coronary syndrome with hypertension, and perioperative myocardial ischaemia |
| Onset, intravenous | About 1 to 3 minutes |
| Duration of effect after stopping | About 5 to 10 minutes |
| Starting infusion dose | 5 to 10 micrograms/minute |
| Titration | Increase by 5 to 20 micrograms/minute every 3 to 5 minutes according to blood pressure, symptoms and adverse effects |
| Usual dose range | 10 to 200 micrograms/minute |
| High-dose treatment | In hypertensive acute pulmonary oedema, some protocols use 200 to 400 micrograms/minute or repeated intravenous boluses. This requires experienced staff, continuous monitoring and a local protocol |
| Adverse effects | Headache, flushing, hypotension, reflex tachycardia, nausea and, rarely, methaemoglobinaemia |
| Tolerance | This can develop with continuous or regular exposure |
| Contraindications | Concomitant phosphodiesterase-5 inhibitor, marked hypotension, preload-dependent right ventricular infarction, and hypertrophic obstructive cardiomyopathy |
| Neurology | Avoid as a routine agent when the intracranial pressure is raised or in hypertensive encephalopathy |
Sildenafil and vardenafil within the past 24 hours, and tadalafil within the past 48 hours, are usually contraindications, but the time limit must be judged according to the drug, the dose, renal function and the local protocol.
A sublingual spray or tablet can be used as a temporary bridge in ischaemic chest pain or hypertensive pulmonary oedema if intravenous treatment is not yet ready. A dose of 0.4 mg is not, however, pharmacokinetically equivalent to a defined amount of intravenous nitroglycerin. Absorption, bioavailability and clinical effect vary, and the previously quoted conversion to ten minutes of infusion in a 75 kg person must therefore not be used for dosing.
High-dose nitrate in acute hypertensive pulmonary oedema can reduce the need for intubation, but the evidence consists mainly of small and heterogeneous studies. Nitroglycerin should be combined with appropriate respiratory support, often continuous positive airway pressure or bilevel ventilation [19,20].
Sodium nitroprusside
Sodium nitroprusside releases nitric oxide and dilates both arterioles and veins. The drug reduces preload and afterload very rapidly. It is potent and easy to titrate but has a considerably more problematic toxicity profile than nicardipine and clevidipine [21].
| Property | Sodium nitroprusside |
|---|---|
| Trade names | Nipride®, Nitropress® |
| Possible use | Acute aortic syndrome after beta blockade, severe acute heart failure, and other refractory hypertensive emergencies when more suitable alternatives are unavailable |
| Onset | Seconds to 1 minute |
| Duration of effect after stopping | About 1 to 10 minutes |
| Starting dose | 0.3 to 0.5 micrograms/kg/minute |
| Titration | Increase in small steps according to continuously measured blood pressure |
| Usual dose range | 0.5 to 3 micrograms/kg/minute |
| Maximum dose | 10 micrograms/kg/minute, for no more than 10 minutes |
| Administration | Continuous infusion protected from light according to the product information |
| Adverse effects | Marked hypotension, nausea, agitation, sweating, tachycardia and metabolic acidosis |
| Organ perfusion | It can raise the intracranial pressure, worsen ventilation–perfusion matching, and affect coronary perfusion unfavourably |
| Toxicity | Cyanide and thiocyanate can accumulate. The risks increase with a high dose and prolonged treatment |
Cyanide is released during metabolism and inhibits mitochondrial oxidative phosphorylation. Suspect toxicity in unexplained lactic acidosis, a falling level of consciousness, tachycardia, a rising venous oxygen saturation, or a diminishing blood pressure effect despite dose increases. Infusion rates above 2 micrograms/kg/minute can exceed the body's capacity to detoxify cyanide, particularly with prolonged treatment or hepatic impairment [21].
Thiocyanate is formed from the conversion of cyanide and is excreted by the kidneys. Renal failure therefore increases above all the risk of thiocyanate accumulation with more prolonged treatment. Neurological symptoms, tinnitus, confusion and seizures can occur. Nitroprusside must be used at the lowest effective dose and for as short a time as possible.
If cyanide toxicity is suspected, the infusion must be stopped immediately and a toxicologist contacted. Sodium thiosulfate and hydroxocobalamin are possible antidotes. The choice and dose must follow the local poisoning protocol. Prophylactic concurrent thiosulfate treatment is used in some units but does not remove the need for monitoring.
Avoid nitroprusside where possible when the intracranial pressure is raised, in acute coronary syndrome, in marked renal or hepatic impairment, and in pregnancy. Leber's hereditary optic neuropathy confers particular sensitivity to cyanide and is a contraindication.
Other drugs
Phentolamine
Phentolamine is a short-acting, non-selective alpha-adrenergic antagonist. It is intended chiefly for catecholamine-driven states, not for the routine treatment of essential hypertension.
| Property | Phentolamine |
|---|---|
| Trade names | Regitine®, Rogitine® |
| First-line indication | Phaeochromocytoma or paraganglioma crisis |
| Other uses | Severe sympathomimetic hypertension and extravasation of alpha-adrenergic vasopressors |
| Onset | About 1 to 2 minutes |
| Duration of effect | About 10 to 30 minutes |
| Bolus dose | 5 mg intravenously. It can be repeated about every 10 minutes according to response |
| Infusion | 0.5 to 1 mg/minute has been used in specialist protocols. Follow the local protocol |
| Adverse effects | Hypotension, reflex tachycardia, arrhythmia, headache, flushing, nausea and angina |
| Caution | Coronary disease, hypovolaemia and acute heart failure |
In phaeochromocytoma and paraganglioma, beta blockade — if it is needed for tachycardia or arrhythmia — must be introduced only after adequate alpha blockade. Beta blockade before alpha blockade can produce unopposed alpha receptor stimulation with further vasoconstriction and a rise in blood pressure [16,22].
Hydralazine
Hydralazine produces direct arteriolar dilatation but has no effect on venous capacitance vessels. The effect after a bolus can be unpredictable and relatively long-lasting. Reflex tachycardia and an increased myocardial oxygen consumption limit its use outside obstetrics.
| Property | Hydralazine |
|---|---|
| Trade name | Apresolin® |
| Principal acute indication | Severe hypertension in pre-eclampsia or eclampsia, according to the obstetric protocol |
| Onset, intravenous | About 10 to 20 minutes |
| Duration of effect | About 2 to 6 hours |
| Obstetric dose | 5 to 10 mg intravenously over about 2 minutes. It can be repeated with 5 to 10 mg after about 20 minutes |
| Usual maximum cumulative intravenous dose in an acute obstetric protocol | 20 mg |
| Intramuscular alternative | 10 mg, with possible repetition according to the obstetric protocol |
| Adverse effects | Reflex tachycardia, headache, flushing, nausea, hypotension and angina |
| Avoid, or use with great caution, in | Acute coronary syndrome, aortic dissection, tachycardia, acute pulmonary oedema, and intracranial disease where precise titration is required |
The previously quoted doses of 10 to 40 mg intravenously every four to six hours and an infusion of up to 25 mg/hour are not appropriate as general treatment for a hypertensive emergency. They carry a risk of accumulation and of hypotension that is difficult to control. Outside obstetrics there are usually more predictable alternatives.
Pregnancy and eclampsia
Acute severe hypertension in pregnancy is usually defined as a persistent systolic blood pressure of at least 160 mmHg or a diastolic blood pressure of at least 110 mmHg. Treatment should be started promptly, usually within an hour, to reduce the risk of intracerebral haemorrhage and other maternal complications [23,24].
Intravenous labetalol, intravenous hydralazine and oral nifedipine are established first-line options. Systematic comparisons do not show any definite general superiority for one agent, although oral nifedipine has in several analyses given rapid and reliable blood pressure control [23,25].
| Drug | Example of an acute regimen |
|---|---|
| Labetalol | 20 mg intravenously, then 40 mg after 10 minutes and 80 mg after a further 10 minutes if the blood pressure persists, to a maximum of 220 to 300 mg depending on the local protocol |
| Hydralazine | 5 to 10 mg intravenously, then 5 to 10 mg after about 20 minutes, usually to a maximum of 20 mg |
| Nifedipine | 10 mg orally as an immediate-release preparation, which can be repeated after 20 minutes according to the obstetric protocol. It must be swallowed, not given sublingually |
In eclampsia, magnesium sulfate is the first-line treatment to terminate and prevent seizures. Blood pressure lowering does not replace magnesium sulfate, and magnesium sulfate does not replace antihypertensive treatment. The definitive treatment is delivery after maternal stabilisation [26].
ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy. Nitroprusside should be avoided if a safer alternative exists, because of the risk of fetal cyanide and thiocyanate exposure. Labetalol must be used with caution in asthma, bradycardia and heart failure. Hydralazine is unsuitable in marked tachycardia.
Swedish obstetric dosing schedules and drug choices may differ somewhat from international guidelines. Always follow the local obstetric protocol and involve the obstetrician, the anaesthetist and the neonatologist early.
Practical monitoring
The following should be documented before and during treatment:
- Correct blood pressure measurement with an appropriate cuff, in both arms initially where possible.
- Neurological status, level of consciousness and any focal neurological findings.
- Heart rate, rhythm, oxygen saturation and continuous ECG.
- Urine output, creatinine, electrolytes and acid–base status.
- Chest pain, ECG changes and troponin in suspected myocardial ischaemia.
- Signs of pulmonary oedema and the need for non-invasive or invasive respiratory support.
- Fundoscopy where malignant hypertension is suspected.
- Medication, adherence, recent withdrawal, over-the-counter preparations and stimulants.
- A pregnancy test in anyone who may be pregnant.
- Clinical signs of hypoperfusion after every substantial change of dose.
Once the acute target has been achieved, a long-acting oral regimen must be planned. The timing of its introduction depends on the target organ damage and on the duration of effect of the intravenous agent. Overlap is often needed before the infusion is stopped, particularly after clevidipine or nitroprusside. At the same time, investigate and treat precipitating factors such as poor adherence, withdrawal of clonidine or a beta blocker, renal disease, primary aldosteronism, renovascular disease, phaeochromocytoma, drug interactions and sympathomimetics [4,27].
References
- Bress AP et al. The Management of Elevated Blood Pressure in the Acute Care Setting: A Scientific Statement From the American Heart Association. Hypertension 2024. PMID: 38804130
- Wilson LM et al. Management of Inpatient Elevated Blood Pressures: A Systematic Review of Clinical Practice Guidelines. Ann Intern Med 2024. PMID: 38560900
- van den Born BH et al. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur Heart J Cardiovasc Pharmacother 2019. PMID: 30165588
- Kulkarni S et al. Management of hypertensive crisis: British and Irish Hypertension Society Position document. J Hum Hypertens 2023. PMID: 36418425
- Perez MI, Musini VM. Pharmacological interventions for hypertensive emergencies. Cochrane Database Syst Rev 2008. PMID: 18254026
- Balahura AM et al. The Management of Hypertensive Emergencies, Is There a Magical Prescription for All? J Clin Med 2022. PMID: 35683521
- Jeong HS et al. Update of the Korean Clinical Practice Guidelines for Stroke: Blood Pressure Management. J Clin Neurol 2025. PMID: 40878301
- Bath PM, Krishnan K. Interventions for deliberately altering blood pressure in acute stroke. Cochrane Database Syst Rev 2014. PMID: 25353321
- Maagaard M et al. Interventions for altering blood pressure in people with acute subarachnoid haemorrhage. Cochrane Database Syst Rev 2021. PMID: 34787310
- Awad AS, Goldberg ME. Role of clevidipine butyrate in the treatment of acute hypertension in the critical care setting: a review. Vasc Health Risk Manag 2010. PMID: 20730061
- Peacock WF et al. Clevidipine for severe hypertension in patients with renal dysfunction: a VELOCITY trial analysis. Blood Press Suppl 2011. PMID: 21091269
- Aronson S et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg 2008. PMID: 18806012
- Cannon CM et al. Intravenous nicardipine and labetalol use in hypertensive patients with signs or symptoms suggestive of end organ damage in the emergency department: a subgroup analysis of the CLUE trial. BMJ Open 2013. PMID: 23535700
- Rhoney D, Peacock WF. Intravenous therapy for hypertensive emergencies, part 2. Am J Health Syst Pharm 2009. PMID: 19667001
- Wiest D. Esmolol. A review of its therapeutic efficacy and pharmacokinetic characteristics. Clin Pharmacokinet 1995. PMID: 7758250
- Calissendorff J et al. Pheochromocytomas and Abdominal Paragangliomas: A Practical Guidance. Cancers 2022. PMID: 35205664
- Mladěnka P et al. Comprehensive review of cardiovascular toxicity of drugs and related agents. Med Res Rev 2018. PMID: 29315692
- Brogden RN, Markham A. Fenoldopam: a review of its pharmacodynamic and pharmacokinetic properties and intravenous clinical potential in the management of hypertensive urgencies and emergencies. Drugs 1997. PMID: 9339965
- Twiner MJ et al. Nitroglycerin Use in the Emergency Department: Current Perspectives. Open Access Emerg Med 2022. PMID: 35847764
- Hodroge SS et al. Adult Patients with Respiratory Distress: Current Evidence based Recommendations for Prehospital Care. West J Emerg Med 2020. PMID: 32726255
- Hottinger DG et al. Sodium nitroprusside in 2014: A clinical concepts review. J Anaesthesiol Clin Pharmacol 2014. PMID: 25425768
- Khan NN et al. Management Strategies for Hypertensive Crisis: A Systematic Review. Cureus 2024. PMID: 39262522
- Scott G et al. Guidelines, similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension. Am J Obstet Gynecol 2022. PMID: 32828743
- Cífková R et al. Peripartum management of hypertension: a position paper of the ESC Council on Hypertension and the European Society of Hypertension. Eur Heart J Cardiovasc Pharmacother 2020. PMID: 31841131
- Conti Ramsden F et al. Pharmacotherapeutic options for the treatment of hypertension in pregnancy. Expert Opin Pharmacother 2024. PMID: 39225514
- Katsi V et al. Diagnosis and Treatment of Eclampsia. J Cardiovasc Dev Dis 2024. PMID: 39330315
- Tsige AW, Ayele SG. Malignant hypertension: current challenges, prevention strategies, and future perspectives. Front Cardiovasc Med 2024. PMID: 39776865
