Hypertensive Crises: Diagnosis and Management in the Emergency Room

Home , Hypertensive crisis, Hypertensive emergency

European Review for Medical and Pharmacological Sciences 2004; 8: 143-152 Hypertensive crises: diagnosis and management in the emergency room

A. MIGNECO, V. OJETTI, A. DE LORENZO**, N. GENTILONI SILVERI, L. SAVI*

Dept. of Emergency Medicine, Catholic University - Rome (Italy) *Dept. of Internal Medicine, Catholic University - Rome (Italy) **Human Nutrition Unit, University of Tor Vergata - Rome (Italy)

Abstract. – Hypertensive crises are com- by the absolute BP levels, but also by the monly observed in an emergency room. magnitude and the rate of the pressure in- Regardless blood pressure values, hyperten- crease and by the underlying conditions3,4. sive crises are classified in emergencies, characterized by life-threatening acute organ dam- For instance, blood pressure levels in eclamp- age, and urgencies, with no evidence of acute sia may be only slightly elevated; neverthe- or progressive organ injury. In an hypertensive less, immediate treatment of hypertension in emergency an appropriate and immediate man- this setting is mandatory. agement with parenteral drugs is mandatory, Hypertensive crises are traditionally subdi- while in an hypertensive urgency blood pres- vided in hypertensive emergencies and ur- sure should be decreased within 24-48 h with 5-7 orally active agents. gencies . This article reviews the spectrum of clinical The presence of acute or progressive life syndromes that comprise hypertensive emer- threatening organ damage such as acute coro- gencies, focusing on specific drugs and thera- nary syndrome, acute left ventricular failure peutic strategies available in the emergency with pulmonary oedema, eclampsia, aortic department, based on current literature. dissection, acute renal failure, hypertensive Since no randomized prospective trials are encephalopathy and haemorragic/ischaemic available, an evidence-based approach recom- mending an optimal therapeutical management stroke constitutes an hypertensive emer- 5-7 is not possible. Much of the therapy is there- gency . Many authors consider also accelerat- fore entirely empirical and based on the under- ed-malignant hypertension an emergency, be- lying pathophysiologic and clinical findings. cause sudden occurrence of complications such Further studies are needed to clarify patho- as stroke, acute renal failure or acute coronary physiologic mechanisms in order to optimize syndrome in this setting is possible8-10. therapeutic approach. In most hypertensive emergencies, BP Key Words: should be lowered within minutes using Hypertension, Hypertensive emergency, Hypertensive parental drugs1,5,6. urgency, Hypertensive crises, Hypertensive complication, An hypertensive urgency is an hyperten- Treatment. sive crises without acute or progressive organ damage, and BP should be lowered in 24-48 hours to prevent development of acute organ damage1,5,7. According to the JNC VII, hypertensive urgencies include upper levels of Introduction stage II hypertension with symptoms like headache, dizziness, severe anxiety, epistaxis Definition and shortness of breath. Some authors in- Hypertensive crisis is defined as a critical clude in the definition also hypertensive elevation of blood pressure in which diastolic crises in patients without evidence of acute or blood pressure (BP) generally exceeds 120 progressive organ damage but at high risk for mmHg1,2. This threshold value is, however, developing new injury (patients with known not univocally established, since the severity target organ diseases such as chronic is- of the clinical picture is not only determined chaemic heart disease or previous stroke)11.

143 A. Migneco, V. Ojetti, A. De Lorenzo, N. Gentiloni Silveri, L. Savi

Casual detection of asymptomatic high BP initiated. Proinflammatory and adhesion mol- levels without any sign of acute or progres- ecules are released from the impaired en- sive organ involvement may be defined as dothelial cell layer, promoting local perme- simple blood pressure rise11. Simple blood ability, inflammation and vasoconstriction15. pressure rise may further be classified as The clinical picture of an hypertensive transient hypertension (generally a cardiovas- crises may range from an asymptomatic pre- cular response to pain or anxiety) or stable sentation to specific symptoms characterizing uncomplicated hypertension12. an acute organ damage (dyspnea, chest pain, neurological disorders). In the absence of or- Ethiology, Pathogenesis, Clinical Picture gan manifestations the patient may complain and Diagnosis about non-specific symptoms such as palpita- Any disorder that causes hypertension can tions, headache, dizziness. give rise to a hypertensive emergency (Table By documenting the medical history, the I). The rate of change in blood pressure de- medical status and by simple diagnostic proce- termines the likelihood that an acute hyper- dures (ECG, fundoscopy, laboratory exams, tensive syndrome will develop4. Pre-existing and when indicated, chest ray, cerebral or chest hypertension may lower the probability of an CT scan) the differential diagnosis between hypertensive emergency through adaptive emergency and urgency can generally be estab- vascular changes that protect end organs lished at the emergency site within a very short from acute changes in BP13. period of time. This approach may also give The pathophysiology of the hypertensive some clues to define the cause of the hyperten- crises is complex and incompletely under- sive crises (e.g., cocaine abuse, pheochromocy- stood: an initial abrupt rise in vascular resis- toma, poorly controlled or previously un- tance seems to be a necessary first step. This known stage II hypertension), guiding to a increased vasoreactivity may be precipitated more appropriate therapy. When an hyperten- by the release of vasodynamic substances such sive emergency is suspected, treatment should as norepinephrine and angiotensin II and can be started as soon as possible, even before the occur as a result of relative hypovolemia13,14. results of these exams are available. The compensatory endothelial vasodilatory responses are overwhelmed, leading to endothelial decompensation, which promotes further rises in BP13. Thus, a vicious circle, Management of with progressive increases on vascular resis- Hypertensive Emergencies tance and further endothelial dysfunction is Several parenteral agents are available for the treatment of hypertensive emergencies Table I. Causes of hypertensive emergencies. (Table II). Intravenous agents are generally preferred in this setting, since the effect of • Essential hypertension: poorly controlled blood the treatment is rapid and occurs within a cal- pressure, antihypertensive drugs withdrawal culable period of time13. Moreover, intra- • Renal parenchymal diseases: acute glomeru- venous treatment can be better regulated lonephritis, vasculitis, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura than medication administered orally or by the • Renovascular diseases sublingual route . • Endocrine diseases: pheocromocytoma, Cushing’s Before administering the treatment, the syndrome, renin secreting tumors, mineralcorti- risk of worsening of the end-organ damage coid hypertension (rare) must be weighed against the risk of rapid • Drugs: cocaine, sympathomimetics, erythropoi- blood pressure lowering. Gradually decrease etin, cyclosporine, interactions with monoamine- of mean BP level while minimizing the risk of oxidase inhibitors (tyramine), amphetamines hypoperfusion is the most important thera- • Autonomic hyperactivity: Guillame-Barrè syn- peutic principle in this setting16. For instance, drome, acute intermittent porphyria patients with chronic hypertension have an • Central nervous system disorders: head injury, altered cerebral autoregulation curve17, and cerebral infarction/haemorrhage, brain tumors • Eclampsia acute normotension would lead to cerebral hypoperfusion.

144 Hypertensive crises: diagnosis and management in the emergency room

Table II. Parenteral drugs for treatment of hypertensive emergencies: pharmacological properties.

Drug Dose Onset of Duration Mechanism action of action of action

Labetalol 20-80 mg iv boluses or 10 min 3-6 h α/β-adrenergic 0.5-2 mg/min by infusion blocker

Esmolol 250-500 mg/kg/min 1-2 min 10-30 min β-adrenergic blocker iv bolus, then 50-100 µg /kg/min by infusion

Phentolamine 5-15 mg iv boluses 1-2 min 10-30 min α-adrenergic antagonist

Urapidil 25 mg iv boluses or 3-5 min 4-6 h α-adrenergic 5-40 mg/h by infusion antagonist

Fenoldopam 0.1-0.3 mg/kg/min 5 min 30 min Dopamine 1 by infusion receptor agonist

Nicardipine 5-15 mg/h by infusion 5-10 min 15-30 min Calcium-channel blocker

Enalaprilat 1.25-5 mg boluses 15-30 min 6-12 h ACE inhibitor every 6h

Sodium 0.25-10 mg/kg/min Immediate 1-2 min Nitric oxid Nitroprussiate by infusion compound direct venous and arterial vasodilator

Nitroglicerine 5-100 mg/min 2-5 min 5–10 min Nitric oxid by infusion compound direct venous and arterial vasodilator (mainly venous)

Hydralazine 10-20 mg iv 10–20 min 1-4 h Direct vasodilator boluses

To avoid cerebral, coronary and renal is- the reliable effectiveness and on the con- chemia, mean BP levels should be reduced traindications of the drugs (Table 3). Other approximately by 25% within few minutes, selection criteria are duration of pressure reaching the goal of 160/100 mmHg within 2- elevation and underlying conditions (e.g., 6 hours5,18. BP should then be normalized in prior cardiovascular, cerebrovascular or re- the following 24-48 h. Patients with aortic dis- nal disorders). section5 or pulmonary oedema19 are excepted Diuretics should generally be avoided un- from the rule of gradual BP reduction: in less there is evidence of left ventricular fail- these cases BP must be reduced as soon as ure and pulmonary oedema, because many possible to normal values or even lower. On patients have or develop hypovolemia during the other hand, reduction of BP in stroke has such emergencies, possibly as a result of pres- been matter of debate for years, since a de- sure induced natriuresis1,20. crease of BP values in this setting may wors- Patients with an hypertensive emergency en the cerebral ischemic damage13. should be admitted to an Intensive Care Unit The choice of the drug greatly depends for continuous BP monitoring and parenteral on the existing organ failure as well as on drug administration5.

145 A. Migneco, V. Ojetti, A. De Lorenzo, N. Gentiloni Silveri, L. Savi

Table III. Parenteral drugs for the treatment of hypertensive emergencies: indications, contraindications and side- effects.

Drug Adverse effects Special Indications Contraindications

Labetalol Vomiting, Most hypertensive Heart failure asthma bronchocostriction emergencies: in particular II degree heart block dizziness, heart block acute coronary syndrome aortic dissection,eclampsia

Esmolol Nausea bronchocostriction Acute coronary syndrome Heart failure asthma heart block aortic dissection bradycardia II degree heart block

Phentolamine Tachycardia, flushing Catecholamine excess Acute coronary syndrome headache aortic dissection

Urapidil Hypotension headache Most hypertensive dizziness emergencies

Fenoldopam Headache, dizziness flushing, Renal failure Glaucoma tachycardia hypokalemia

Nicardipine Tachycardia, headache, flushing Renal failure stroke Heart failure acute h. encephalopathy coronary syndrome aortic dissection

Enalaprilat Variable response with Left ventricular failure Acute coronary possible BP precipitous fall syndrome

Nitroprussiate Vomiting, sweating, thiocynate Most hypertensive Caution with high and cyanide intoxication emergencies intracranial pressure

Nitroglycerine Headache, vomiting, tolerance Acute coronary syndrome left ventricular failure

Hydralazine Tachycardia, flushing headache, Eclampsia Acute coronary sindrome, vomiting aortic dissection

Stroke antihypertensive treatment should be with- Management of the hypertensive crises dur- held unless the diastolic BP is > 120 mmHg ing ischaemic stroke is a therapeutic dilemma, or the systolic BP is > 220 mmHg24,25. Aim of because a rapid fall of BP levels may compro- the therapy should be a cautious reduction of mise cerebral blood flow, leading to hypoper- BP by about 10% to 15%25. If the patient is fusion of the peri-infarction area with conse- eligible for thrombolytic therapy, careful quent worsening of the ischaemic damage21,22. management of BP is critical, because exces- Furthermore, in many patients with acute sive high pressure levels are associated with stroke, hypertension resolves spontaneously high risk of parenchymal haemorrhage after within 48 h23. On the other hand severe hyper- thrombolysis26. In these cases BP values tension may lead to direct vascular damage, should be kept < 185/110 mmHg at the time extension of the perifocal oedema and hemor- of the treatment and in the following 24 h24. rhagic transformation of the infarction24. Haemorrhagic stroke requires more aggres- Optimal management of hypertensive sive blood pressure control: the American crises during ischaemic stroke has not been Heart Association guidelines recommend to established. The general agreement is that keep mean arterial pressure < 130 mmHg27.

146 Hypertensive crises: diagnosis and management in the emergency room

Management of hypertension in subarach- The pathogenesis of hypertensive en- noid haemorrhage should be targeted toward cephalopathy seems to be related to cere- averting re-haemorrhage on one hand, and brovascular endothelial dysfunction with dis- reduced cerebral perfusion, due to arteriolar ruption of the blood-brain barrier resulting in vasospasm, with secondary brain ischemia, on cerebral oedema and microhaemorrhage for- the other hand. There are no data or consen- mation13. sus about optimal BP values in this setting. Symptoms are acute or subacute onset of Some authors advise to maintain mean and lethargy, confusion, headache, visual distur- systolic arterial pressure 15% above base- bance and seizures. If not adequately treated line28, while other authors29 suggest a more hypertensive encephalopathy can progress to aggressive treatment maintaining the peak massive cerebral haemorrhage, coma and systolic pressure 20 % below baseline. death13. Centrally acting drugs such as clonidine Suitable drugs in the management of hy- should be avoided because of their capacity pertensive encephalopathy include labetalol, to interfere with mental status1. Parental enalaprilat, nicardipine, urapidil, hydra- agents, such as labetalol, easily titrated and lazine13,16. Although sodium nitroprussiate with minimal dilatory effect on cerebral ves- may increase intracranial pressure, many ex- sel are the first choice therapy24. Other possi- perts continue to advocate it’s use13,21. ble agents are Esmolol, Enalaprilat30, Clonidine should be avoided because it is a Urapidil31 or Nicardipine16. In some cases central nervous system depressant1,13. In el- combination of these drugs may be necessary derly patients and in those with pre-existing for adequate arterial pressure control. Some hypertension, altered cerebral autoregulation authors suggest addition of nitroprussiate if limits demand cautious treatment: overzeal- hypertension is resistant to β-blockers or ous BP pressure lowering may determine ACE inhibitors24. This drug should be ad- cerebral hypoperfusion, with worsening of ministered very cautiously, if at all, since its the neurological status and stroke13. vasodilatory properties may lead to increase intracranial pressure exacerbating cerebral Acute Coronary Syndrome ischemia28. Acute coronary syndromes include acute Nimodipine is currently administered in myocardial infarction with ST segment eleva- subarachnoid haemorrhage to prevent cere- tion, acute myocardial infarction without ST bral arteriolar vasospasm29. Since nimodipine segment elevation and unstable angina. β- may lower BP, antihypertensive agents blockers, nitrates, oxygen and aspirin are tra- should be given only if nimodipine has been ditionally emergency department first line ineffective on systemic arterial pressure. therapy in acute coronary syndrome34-37. In particular, the positive effects on survival and Hypertensive Encephalopathy on reduction of the infarction area of beta Hypertensive encephalopathy is defined blockade during acute myocardial infarction as an acute organic brain syndrome occur- are well known38,39. Since β-blockers and ni- ring as a result of failure of the upper limit trates effectively lower BP, they are the first of cerebral vascular autoregulation13. choice therapy in hypertensive crises during Cerebral blood flow is autoregulated within acute coronary syndrome. Nitrates, and in specific limits: as mean arterial pressure in- particular nitroglycerine, decrease the cardiac creases, compensatory cerebral vasocon- preload, the left ventricular filling pressure striction limits cerebral hyperperfusion. In a and, to a lesser extent, also the cardiac after- normotensive individual cerebral blood flow load inducing arterial dilation: the result is a remains unchanged between mean arterial decrease of myocardial oxygen consumption pressures of 70 and 150 mmHg; in hyperten- and a reduction of arterial pressure lev- sive individuals these limits are shifted to els13,21,37. These drugs also dilate the coronary higher levels (110 and 180 mmHg)10,32,33. arteries, facilitating coronary blood flow. When mean arterial pressure exceeds the It is well known that β-blockers have nega- upper limit of autoregulation, cerebral va- tive chronotropic and inotropic effects, de- sodilation ensues with overperfusion and creasing cardiac output and dramatically re- cerebral oedema11,14. ducing myocardial oxygen demand. The

147 A. Migneco, V. Ojetti, A. De Lorenzo, N. Gentiloni Silveri, L. Savi longer diastolic filling time promotes coro- pooling and decreased ventricular preload. nary blood flow, increasing myocardial perfu- The subsequent diuretic effect further de- sion40. Nevertheless, the magnitude of the BP creases ventricular preload and reduces BP decrease in the first 24 hours after β-blocker levels, thereby positively affecting also the af- administration is not predictable, since the terload mismatch41. ACE-inhibitors may be reduction of the cardiac output determines a useful in this setting14,16. transient reflex rise of the peripheral vascular Drugs decreasing myocardial contractility, resistance. In cases of hypertensive crises such as labetalol, should be avoided. during acute coronary syndrome a more defi- Concomitant therapy with opioids and oxy- nite antihypertensive effect is suitable, and gen supply may enhance the efficacy of anti- labetalol is a reasonable choice. Owing to its hypertensive agents16. competitive β- and α-inhibition properties, labetalol reduces vascular resistance and ar- Acute Aortic Dissection terial BP without induction of reflex tachy- Regardless the type of aortic dissection cardia1,21. and the further management (surgical thera- Dihydropyridines, such as nicardipine, and py, endovascular stent placement, pharmaco- hydralazine should be avoided, since these logical treatment), aim of the first line thera- drugs enhance sympathetic outflow increas- py is to prevent propagation of the dissection. ing the cardiac work. Advancement of the dissection critically depends on the hydrodynamic forces in the Left Ventricular Failure and bloodstream: these are mainly related to the Pulmonary Oedema mean BP levels and to the steepness of the The pathogenesis of acute left ventricular pulsewave (dP/dt)42. Aim of the treatment is failure is related to a critical interaction be- to reduce the force of the left ventricular con- tween progressive decrease in cardiac systolic tractions, in order to decrease the steepness performance and an acute increase in sys- of the aortic pulsewave on one hand, and to temic vascular resistance. This leads to a de- reduce cardiac output with a fall of mean BP crease in cardiac index and increase in left levels on the other hand. Thus β-blockers, ventricular diastolic filling pressure with a owing to their negative inotropic properties, steep increase in pulmonary venous, and are standard therapy for aortic dissection. hence pulmonary capillary pressure inducing Moreover, the negative chronotropic effect of exudation of fluid from the intravascular β-blockers decrease the number of left ven- compartment into the lung interstitium and tricular contractions per minute, with a fur- alveoli. The consequent decrease of O2 satu- ther reduction of the total pulsatile load on ration leads to myocardial ischemia, further the aortic wall11,42. impairing the cardiac performance19. High BP In cases of hypertensive crises associated levels in this setting worsen the left ventricu- to aortic dissection, a β-blocker (propanolol, lar afterload mismatch decreasing further the esmolol) should be started in addition to ni- cardiac output. troprussiate43. The latter agent should never Immediate goals of the treatment is im- be administered without previous beta block- proving systemic oxygen saturation and in- ade, since the reflex catecholamine release ducing a rapid vasodilation of both arteries secondary to the nitroprussiate induced va- and veins, thus decreasing vascular resis- sodilation may result in an increase in left tance, alleviating afterload mismatch and ventricular contraction force42. Labetalol, a reducing preload of both left and right ven- potent antihypertensive agent with β-blocker tricles19. properties, is an alternative to the combina- Sodium nitroprussiate achieves both ven- tion β-blocker and nitroprussiate42,43. If β- odilation and arterial vasodilation, decreasing blockers are contraindicated, urapidil is a pre- and afterload16,21. Nytroglicerine is a rea- reasonable choice21,31. sonable alternative that has less afterload re- Treatment should be started as soon as the ducing capability, but it may increase myocar- diagnosis of aortic dissection is suspected, and dial blood flow to ischemic areas16,21. the systemic arterial pressure should reach the Intravenous furosemide has immediate ven- lowest levels allowing organ perfusion (sys- odilatory properties, leading to venous blood tolic BP between 100 and 110 mmHg)5,42.

148 Hypertensive crises: diagnosis and management in the emergency room

Eclampsia lent choice13,16. Diuretic use in renal failure Preeclampsia is characterized by hyperten- and severe hypertension may be beneficial or sion diagnosed after 20 weeks gestation (BP deleterious, depending on the patient’s vol- values > 140/90 mmHg) and proteinuria45. ume status13. Other features consistent with severe If hypertension remains severe or refrac- preeclampsia are neurological symptoms such tory, other vasodilators, such as sodium nitro- as headache, visual disturbances, oliguria, prussiate or fenoldopam13,16 can be used. thrombocytopenia, increased liver enzymes and pulmonary oedema. Eclampsia is the new Accelerated-Malignant Hypertension onset of seizures before, during or after labor, Accelerated-malignant hypertension is a not attributable to other causes, in a woman rare form of hypertension characterized by with preeclamsia45. Seizures generally occur as fibrinoid necrosis of arterioles in many vascu- a result of hypertensive encephalopathy. The lar beds47. Accelerated-malignant hyperten- best treatment of preeclampsia or eclampsia is sion may complicate any form of chronic hy- delivery44. If delivery is not possible or war- pertension, but it occurs most commonly in ranted then management should include hos- young black men with underlying renal or pitalization, close observation, antihyperten- renovascular diseases11. The diagnosis is sive treatment and prophylaxis against con- made by the presence of severe hypertension vulsions. Prevention and treatment of eclamp- in association with bilateral retinal haemor- tic seizures is best achieved by administration rhages, cotton wool spots or exudates with or of magnesium sulphate46. Treatment with spe- without papilledema48. Other features of ac- cific antihypertensive agents should be initiat- celerated-malignant hypertension are hemol- ed when diastolic pressure exceeds 105 ysis and thrombocytopenia due to red cell mmHg, or when it increases rapidly from a and platelet fragmentation8. The main com- near normal range to > 100 mmHg14. plications of malignant hypertension are Hydralazine, administered in repeated intra- stroke, myocardial infarction, hypertensive venous boluses is the most commonly used encephalopathy and renal failure. Direct drug in eclampsia14,44. Labetalol is also effec- pressure effects, volume depletion, activation tive in this setting, either as an intravenous of the renin-angiotensin system, imbalanced bolus or by continuous infusion13,14. production of nitric oxid and natriuretic pe- tides and oxidative stress have all been impli- Acute or Progressive Renal Failure cated in the pathogenesis of accelerated-ma- Acute renal failure may be a cause or a lignant hypertension49. consequence of hypertensive emergency11,13. Most of the complications are related to in- Hypertensive emergencies are common in travascular thrombosis due to endothelial patients with renal transplant, especially damage. These abnormalities probably im- those receiving cyclosporine and corticos- prove with good BP control47. teroids13. Severe hypertension in young pa- Treatment of accelerated-malignant hyper- tients should raise the possibility of intrinsic tension should start immediately, and any of acute renal disease, such as acute glomeru- the parenteral antihypertensive agents is ap- lonephritis. Intrarenal vasculitis, sometimes propriate in this setting11: drug selection crite- occurring in scleroderma, is a rare cause of ria are ongoing complications (stroke, acute acute renal failure and consequent blood renal failure, myocardial ischemia) and pre- pressure increase11. On the other hand, accel- existing conditions (previous chronic renal in- erated-malignant hypertension causes fre- sufficiency, heart failure). quently acute renal failure11. The primary goal in the management of new-onset renal insufficiency accompanying severe hypertension is to limit further renal Management of damage through BP control. Antihypertensive Hypertensive Urgencies drugs that preserve renal blood flow, such a calcium antagonists and alfa-adrenergic block- In a hypertensive urgency the patient’s BP ing agents are appropriate13,16. Labetalol, ow- should be reduced within a period of 24 to 48 ing to its alfa-inhibiting properties is an excel- hours. Such adjustment can be achieved on

149 A. Migneco, V. Ojetti, A. De Lorenzo, N. Gentiloni Silveri, L. Savi an out-patient basis, however, only if the pa- tor blocking properties16,21. Treatment of ur- tient can be followed up adequately for early gencies, with less severe hypertension, should detection of a renewed crises5,16,21. Generally include alfa-adrenoceptor blocking agents that oral medications are used for gradual reduc- can be given orally, such as doxazosine. tion of blood pressure5,16. Selection of the an- Cocaine use can result in a typical sympa- tihypertensive agent depends on the patient’s thomimetic syndrome with tachycardia, ar- medical history and on any underlying chron- rhythmias, hypertension, hyperthermia and ic disease. agitation51. Complications include myocar- Stable uncomplicated hypertension should dial ischemia, cerebral infarction, intra- be treated with new oral antihypertensive parenchymal or subarachnoid haemorrhage agents or reinstitution of previous medication and rarely aortic dissection. Severe hyper- if non compliance is a problem. tension is best treated with phentoalamine, Transient hypertension due to pain or anxi- labetalol or nitroprussiate plus β-block- ety is best treated with analgesic or anxiolytic ers16,21. As in pheochromocytoma, β-blockers medications16. alone should be avoided because of para- doxical BP rise, due to unopposed peripheral alfa-adrenergic mediated vasoconstriction. Chest pain usually responds to Management of Catecholamine nytroglicerine. If myocardial infarction de- Induced Hypertensive Crises velops, the combination of nytroglycerine plus labetalol seems the best choice. Catecholamine-induced hypertensive crises Phentolamine is considered second line are characterized by a sudden increase in pre- agent for cocaine-induced hypertensive dominantly α-adrenergic tone21. Catechola- crises with chest pain51. mine-induced crises may present as an hypertensive urgency, or may cause acute end organ damages. The most common causes are ingestion of sympathomimetics, clonidine Conclusions withdrawal, interaction of monoamine oxidase inhibitors with tyramine rich foods (cer- Severely elevated BP subtend different tain beers, wine, chicken liver) and pheochro- clinical entities with markedly different time- mocytoma. lines varying in the immediacy with which Generally, first choice drugs are alfa- they should be treated. adrenoceptor blockers such as phentolamine21. Patients with hypertensive crises are not Pheochromocytoma is a rare chromaffin cell good candidates for prospective randomized tumor producing catecholamines50. Typically trials, and data attesting benefits of acutely patients show sustained or paroxysmal hyper- lowering BP in this condition are not avail- tension with headache, palpitations and sweat- able. Since an evidence-based approach rec- ing. During such crises patients may develop ommending an optimal therapeutical man- end organ damages such as myocardial infarc- agement is not possible, much of the therapy tion, hypertensive encephalopathy, stroke and is entirely empirical and based on the attempt congestive heart failure50. In this setting, im- to best match pathophysiological findings mediate treatment is crucial, and phento- with pharmacologic properties of antihyper- lamine in repeated boluses or in continuous tensive agents. infusion is the best choice. Commonly used al- Choice of the appropriate agent should ternatives are nitroprussiate with β-blockers21 therefore be based on clinical findings, mech- or nicardipine50. β-blockers as exclusive agents anism of action and potential adverse effect. are contraindicated, since unopposed alfa-mediated peripheral vasoconstrinction may lead to further BP rise16,21. If tachycardia, arrhyth- mia or angina are present, beta adrenoceptor References blockers are indicated after an appropriate al- 1) BALES A. Hypertensive crisis. How to tell if it’s an fa adrenoceptor blockade. Possible alternative emergency or an urgency. Postgrad Med 1999; is labetalol, owing to its alfa-beta adrenocep- 105: 119-126, 130.

150 Hypertensive crises: diagnosis and management in the emergency room

2) ZAMPAGLIONE B, PASCALE C, MARCHISIO M, SANTORO A. 19) COTTER G, MOSHKOVITZ YARON, MILOVANOV OLGA,et The use of lacidipine in the management of hy- al. Acute heart failure: a novel approach to its pertensive crises: a comparative study with pathogenesis and treatment. Eur J Heart Failure nifedipine. J Cardiovasc Pharmacol 1994; 23 2002; 4: 227-234. (Suppl 5): S116-118. 20) ORTH H, RITZ E. Sodium depletion in accelerated 3) GIFFORD R. Management of hypertensive crises. hypertension. N Engl J Med 1975; 292: 1133. JAMA 1991; 226: 829-835. 21) HIRSCHL MM. Guidelines for the drug treatment 4) FINNERTY FA. Hypertensive encephalopathy. Am J of hypertensive crises. Drugs 1995; 50: 991- Med 1972; 52: 672-78. 1000.

5) CHOBANIAN AV, BAKRIS GL, BLACK HR, et al. Seventh 22) POWERS WJ. Acute hypertension after stroke: the report of the Joint National Committee on preven- scientific basis for treatment decisions. Neurology tion, detection, evaluation, and treatment of high 1993; 43: 461-467. blood pressure. Hypertension 2003; 42: 1206-1252. 23) PHILIPS SJ. Pathophysiology and management of hy- 6) VIDT DG. Emergency room management of hyper- pertension in acute ischemic stroke. Hypertension tensive urgencies and emergencies. J Clin 1994; 23: 131-136. Hypertens (Greenwich) 2001; 3: 158-64. 24) ADAMS HP, ADAMS RJ, BROTT T, et al. Guidelines for 7) ZAMPAGLIONE B, PASCALE C, MARCHISIO M, CAVALLO- the early management of patients with ischemic PERIN P. Hypertensive urgencies and emergencies. stroke. A scientific statement from the Stroke Prevalence and clinical presentation. Hypertension Council of the American Stroke Association. 1996; 27: 144-147. Stroke 2003; 34: 1056-1083.

8) KHANNA A, MCCULLOUGH PA. Malignant hypertension 25) BATH P. High blood pressure as risk factor and presenting as hemolysis, thrombocytopenia and re- prognostic predictor in acute ischaemic stroke: nal failure. Rev Cardiovasc Med 2003; 4: 255-259. when and how to treat it? Cerebrovascular Dis 2004; 17 (Suppl 1): 51-57. 9) TUNCEL M, RAM VC. Hypertensive emergencies: etiology and management. Am J Cardiovasc 26) NO AUTHORS LISTED. The NINDS t-PA Stroke Study Drugs 2003; 3: 21-31. Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 10) EPSTEIN M. Diagnosis and management of hyperten- 1997; 28: 2109-2118. sive emergencies. Clin Cornestone 1999; 2: 41-54. 27) BRODERICK JP, ADAMS HP, BARSAN W, et al. Guidelines 11) SHAYNE PH, PITTS SR. Severely increased blood for the management of spontaneous intracerebral pressure in the emergency department. Ann hemorrhage: a statement for healthcare profes- Emerg Med 2003; 41: 513-529. sionals from a special writing group of the Stroke 12) SOLDINI M, CARMENINI E, LIGUORI A, BARATTA P, C URCIO Council, American Heart Association. Stroke D, GIANCASPRO G. Guidelines for the management 1999; 30: 905-915. of hypertensive crises and simple blood pressure rise. Literature review and clinical experience. 28) KRAUS JJ, METZLER MD, COPLIN WM. Critical care is- Clin Ter 2002; 153: 329-333. sues in stroke and subarachnoid hemorrhage. Neurol Res 2002; 24 (Suppl 1): S47-S57. 13) VAUGHAN CJ, DELANTY N. Hypertensive emergencies. Lancet 2000; 356: 411-417. 29) SEN J, BELLI A, ALBON H, MORGAN LALEH, PETZOLD A, KITCHEN N. Triple-H therapy in the management of 14) BLUMENFELD JD, LARAGH JH. Management of hyper- aneurismal subarachnoid haemorrhage. Lancet tensive crises: the scientific basis for treatment Neurol 2003; 2: 614-621. decisions. Am J Hypertens 2001; 14 (11 Pt 1): 1154-1167. 30) POWERS WJ, ZAZULIA AR, VIDEEN TO, et al. Autoregulation of cerebral blood flow surrounding 15) OKADA M, MATSUMORI A, ONO K, et al. Cyclic acute (6 to 22 hours) intracerebral hemorrhage. stretch up-regulates production of interleukin-8 Neurology 2001; 57: 18-24. and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human 31) ALIJOTAS-REIG J, BOVE-FARRE I, DE CABO-FRANCES F, endothelial cells. Arterioscler Thromb Vasc Biol ANGLES-COLL R. Effectiveness and safety of pre- 1998; 18: 894-901. hospital urapidil for hypertensive emergencies. Am J Em Med 2001; 19: 130-133. 16) GROSSMAN E, HIRONI AN, MESSERLI FH. Comparative tolerability profile of hypertensive crisis treat- 32) PAVY-LETRAHON A, COSTES-SALON MC, GALINER M, ments. Drug Saf 1998; 19: 99-122. FOURCADE J, LARRUE V. Dynamics of cerebral blood flow autoregulation in hypertensive patients. J 17) STAANGAARD S, PAULSON OB. Cerebral blood flow in Neurol Sci 2002; 195: 139-144. untreated and treated hypertension. Neth J Med 1995; 47: 180-184. 33) EAMES PJ, BLAKE MJ, PANERAI RB, POTTER JF. Cerebral autoregulation indices are unimpaired by hyper- 18) CALHOUN DA, OPARIL S. Treatment of hypertensive tension in middle aged and older people. Am J crises. N Engl J Med 1990; 323: 1177-1183. Hyperten 2003; 16: 746-753.

151 A. Migneco, V. Ojetti, A. De Lorenzo, N. Gentiloni Silveri, L. Savi

34) SHANNON AW, HARRIGAN RA. General pharmacolog- 42) KHAN IA, CHANDRA KN. Clinical, diagnostic, and ic treatment of acute myocardial infarction. Emerg management perspectives of aortic dissection. Med Clin North Am 2001; 19: 417-431. Chest 2002; 122: 311-328.

35) KLONER RA, REZKALLA SH. Cardiac protection during 43) CHEN K, VARON J, WENKER OC, JUDGE DK, FROMM acute myocardial infarction: where do we stand RE, STERNBACH GL. Acute thoracic aortic dissection: 2004? J Am Coll Cardiol 2004; 44: 276-286. the basics. J Emerg Med 1997; 15: 859-867.

36) POLLACK CV, GIBLER WB. 2000 ACC/AHA guidelines 44) LIPSTEIN H, LEE CC, CRUPI RS. A current concept of for the management of patients with unstable eclampsia. Am J Emerg Med 2003; 21: 223- angina and non-ST-segment elevation myocardial 226. infarction: a practical summary for emergency 45) OPEZ LERA Main clinical subtypes of eclamp- physicians. Ann Emerg Med 2001; 38: 229-240. L -L M. sia. Am J Obstet Gynecol 1992; 166: 4-9. 37) BERTRAND ME, SIMOONS ML, FOX KAA, et al. 46) ITLIN IBAI Magnesium sulphate therapy Management of acute coronary syndromes in pa- W AG, S BM. in preeclampsia and eclampsia. Obstet Gynecol tients presenting without persistent ST-segment 1998; 92: 883-889. elevation. The Task Force on the Management of Acute Coronary Syndromes of the European 47) LIP GYH, EDMUNDS E, LEONG LI SAW HEE F, B LANN AD, Society of Cardiology. Eur Heart J 2002; 23: BEEVERS DG. A cross-sectional, diurnal, and follow- 1809-1840. up study of platelet activation and endothelial dysfunction in malignant phase hypertension. Am 38) NO AUTHORS LISTED. Metoprolol in acute myocardial J Hypertens 2001; 14: 823-828. infarction. Patient population. The MIAMI Trial Research Group. Am J Cardiol 1985; 56: 10G-14G. 48) LIP GYH, BEEVERS M, BEEVERS DG. Complications and survival of 315 patients with malignant-phase 39) NO AUTHORS LISTED. Mechanisms for the early mor- hypertension. J Hypertens 1995; 13: 915-924. tality reduction produced by beta-blockade started early in acute myocardial infarction: ISIS-1. 49) COLLIDGE TA, LAMMIE GA, FLEMING S, MULLINS JJ. The ISIS-1 (First International Study of Infarct role of the renin-angiotensin system in malignant Survival) Collaborative Group. Lancet 1988; vascular injury affecting the systemic and cere- 1(8591): 921-923. bral circulations. Progr Biophys Mol Biol 2004; 84: 301-319. 40) GARG J, MESSERLI AW, BAKRIS GL. Evaluation and treatment of patients with systemic hypertension. 50) BROUWERS FM, LENDERS JWM, EISENHOFER G, PACAK K. Circulation 2002; 105: 2458-2461. Pheochromocytoma as an endocrine emergency. Rev Endoc Metabol Disord 2003; 4: 121-128. 41) JHUND PS, DAVIE AP, MCMURRAY JJV. Aspirin inhibits the acute venodilator response to furosemide in 51) ZIMMERMAN JL. Poisonings and overdose in the in- patients with chronic heart failure. J Am Coll tensive care unit: general and specific manage- Cardiol 2001; 37: 1234-1238. ment issues. Crit Care Med 2003; 31: 2794-2801.

152