Behandlung des hypertensiven Notfalls

DEFINITION, PATHOPHYSIOLOGY, THERAPY: The hypertensive crisis is characterized by a massive, acute rise in blood pressure. Patients with underlying hypertensive disease usually have an increase in systolic blood pressure values > 220 mmHg and diastolic values > 120 mmHg. The severity of the condition, however, is not determined by the absolute blood pressure level but by the magnitude of the acute increase in blood pressure. Thus, in the presence of primarily normotensive baseline values (such as those in eclampsia), even a systolic blood pressure > 170 mmHg may lead to a life-threatening condition. The most important causes are non-compliance (reduction or interruption of therapy), inadequate therapy, endocrine disease, renal (vessel) disease, pregnancy and intoxication (drugs). The management of this condition greatly depends on whether the patient has a hypertensive crisis with organ manifestation (hypertensive emergency) or a crisis without organ manifestation (hypertensive urgency). By documenting the medical history, the medical status and by simple diagnostic procedures, the differential diagnosis can be established at the emergency site within a very short period of time. In the absence of organ manifestations (hypertensive urgency) the patient may have non-specific symptoms such as palpitations, headache, malaise and a general feeling of illness in addition to the increase in blood pressure. In a hypertensive urgency the patient's blood pressure should not be reduced within a few minutes but within a period of 24 to 48 hours. Such adjustment can be achieved on an out-patient basis, however, only if the patient can be followed up adequately for early detection of a renewed attack. In the absence of follow-up facilities, the patient's blood pressure should be reduced over a period of 4 to 6 hours, if necessary in an out-patient emergency service. While intravenous medication is given preference when a rapid effect is desired, oral medication may be used for gradual reduction on an out-patient basis, depending on the patient's medical history and on any underlying chronic disease. Organ manifestations in the course of a hypertensive emergency concern the cardiovascular system and are associated with the symptoms of acute left-ventricular heart failure, the acute coronary syndrome or acute aortic dissection. In the brain the patient may have symptoms of hypertensive encephalopathy, hemorrhage, ischemia; in the kidney he/she may develop acute failure. The patient's blood pressure should be reduced rapidly during the treatment. It should not be reduced to the normal value, but by approximately 20-30% of the baseline value. The reason for a stepwise reduction in blood pressure is the fact that patients with chronic hypertension have an altered autoregulation curve. Acute normotension would lead to hypoperfusion in these patients. Those with aortic dissection or pulmonary edema are excepted from the rule of gradual blood pressure reduction. In the presence of these diseases, blood pressure must be reduced rapidly to normal values. Patients with a hypertensive emergency should always be admitted to the hospital. Parenteral treatment is given preference, since the effect of the treatment is rapid and occurs within a calculable period of time. Thus, parenteral treatment can also be better regulated than medication administered orally or by the sublingual route. Several antihypertensives are available for this purpose. The selection of the substance greatly depends on the existing organ failure as well as the reliable effectiveness and the regulability of the applied antihypertensive.     

Emergency Room Management of Hypertensive Urgencies and Emergencies

Hypertensive crisis affects upward of 500,000 Americans each year. Although the incidence of hypertensive crisis is low, affecting fewer than 1% of hypertensive adults, more than 50 million adult Americans suffer from hypertension. Presentation of a patient with severe hypertension to the emergency room demands immediate evaluation, prompt recognition of a hypertensive emergency or urgency, and the prompt institution of appropriate therapeutic measures to prevent progression of target-organ damage and to avoid a catastrophic event. Hypertensive emergencies are severe elevations in blood pressure that are complicated by evidence of progressive target-organ dysfunction such as coronary ischemia, disordered cerebral function, a cerebrovascular event, pulmonary edema, or renal failure. Although therapy with parenteral antihypertensive agents may be initiated in the emergency department, these patients warrant prompt admission to an intensive care unit where continuous monitoring of blood pressure can be assured during therapy.     

Treatment of hypertensive urgencies and emergencies

Although systemic hypertension is a common clinical condition, hypertensive emergencies are unusual in clinical practice. There are some situations, however, that qualify as hypertensive emergencies or urgencies. It is important, therefore, to diagnose these acute conditions, in which immediate treatment of hypertension is indicated. The diagnosis of hypertensive emergencies depends on consideration of the clinical manifestations as well as the absolute level of blood pressure. Manifestations of hypertensive emergencies can be quite profound, but they vary depending on the target organ that is affected. Thus, an accurate clinical diagnosis is necessary to render appropriate therapy. Fortunately, effective drug therapy is available to lower the blood pressure quickly in hypertensive emergencies. Physicians should be familiar with the pharmacologic and clinical actions of drugs in treating hypertensive emergencies. With proper clinical diagnosis, hypertensive emergencies can be successfully treated, and complications can be largely prevented with timely intervention.     

ESH-ESC Guidelines for the Management of Hypertension

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension.The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated.The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics.Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present.In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.     

How should we treat a hypertensive emergency?

Hypertensive emergencies are life-threatening situations caused by acute blood pressure elevation. They require immediate treatment with antihypertensive drugs. Such emergencies include hypertensive crisis, acute left ventricular heart failure or intracranial bleeding in patients with hypertension, malignant hypertension resistant to treatment, and serious blood pressure elevations after vascular surgery. A hypertensive crisis may be defined as a sudden increase in systolic and diastolic blood pressure that causes functional disturbances of the central nervous system, the heart or the kidneys. In patients with hypertensive crisis, treatment should be started with an alpha receptor-blocking agent if pheochromocytoma has not been excluded by previous workup. Antihypertensive agents with a rapid onset of action--nifedipine, clonidine, dihydralazine, diazoxide and sodium nitroprusside--are being used.     

Clinical features and management of selected hypertensive emergencies

A hypertensive emergency, defined as an elevated blood pressure with evidence of acute target organ damage, can manifest in many forms, including neurological, cardiac, renal, and obstetric. After diagnosis, effective parenteral antihypertensive therapy (typically, nitroprusside starting at 0.5 microg/kg/min, but some physicians prefer fenoldopam or nicardipine) should be given in the hospital. In general, blood pressure should be reduced about 10% during the first hour and another 15% gradually over 2-3 more hours. The exception is aortic dissection, for which treatment includes a b blocker, and the target is systolic blood pressure <120 mm Hg after 20 minutes. Oral antihypertensive therapy can usually be instituted after 6-12 hours of parenteral therapy. Consideration should be given to secondary causes of hypertension after transfer from the intensive care unit. Because of advances in antihypertensive therapy and management, "malignant hypertension" should be malignant no longer.     

Hypertensive emergencies and urgencies: Pathophysiology and clinical aspects

A hypertensive urgency should be distinguished from a hypertensive emergency. Although the distinction may not always be obvious, certain guidelines may help the clinician determine which therapeutic approaches are most appropriate for each patient. Hypertensive emergencies include those conditions in which new or progressive severe end-organ damage is present and a delay in appropriate therapy might result in permanent damage, progression of complications, and a poor prognosis. Hypertensive urgencies include those conditions with minimal to no obvious end-organ damage in which blood pressure should be lowered expeditiously. The risk of immediate complications or organ damage is less likely to occur, and thus the immediate prognosis is better, although the ultimate prognosis, if untreated, is poor. There is a marked individual, racial, sexual, and age difference in the ability to tolerate high intraarterial pressure, as evidenced by patients' symptoms and signs of end-organ damage.Patients may have no symptoms of elevated blood pressure until significant intraarterial levels are reached. If symptoms are present, they may include headache, dizziness, blurred vision, shortness of breath (especially with exertion), chest pain, rapid pulse, palpitations, malaise and fatigue, nocturia, or pedal edema.^7,11–14 Signs of hypertensive disease vary and depend not only on the level of blood pressure but also include funduscopic changes with arteriolar narrowing, atrioventricular nicking, hemorrhages, exudates or papilledema, central nervous system changes and neurologic abnormalities, cardiac changes with gallop rhythm, cardiomegaly, tachycardia, ectopic ventricular beats, left ventricular hypertrophy or signs of congestive heart failure, pulmonary edema, and signs of renal insufficiency.^7,11–14Although there is a definite correlation between the level of blood pressure and end-organ damage, there is no definite systolic or diastolic level of blood pressure that induces end-organ damage. Some patients may tolerate very high blood pressures with few symptoms or signs, whereas others may manifest end-organ damage at lower blood pressures. Thus, the definition of hypertensive emergency and urgency depends on the clinical assessment of the blood pressure level and clinical and laboratory assessments of end-organ damage. The absolute blood pressure in itself does not determine the seriousness of the clinical situation, the expediency of treatment, or the need for in-hospital monitoring in a critical care unit.It is important not to lower the blood pressure precipitously or to a subnormal level particularly in patients with end-organ damage. Such treatment may critically reduce blood flow and perfusion to vital organs and induce a cerebrovascular accident, myocardial ischemia, or renal failure. A smooth, gradual reduction in blood pressure is crucial to patient management with oral or parenteral antihypertensive drugs. However, in hypertensive emergencies blood pressure control should be accomplished within 1 hour, whereas with hypertensive urgencies control should be within 24 hours.Those patients who have hypertensive emergencies with malignant hypertension and end-organ damage should be admitted to a hospital intensive care unit for evaluation and treatment. These patients have a diffuse arteritis, as of a result of their hypertension, that may take 4 to 6 weeks to heal. Many patients who present with diastolic blood pressure 120 mm Hg or greater will be found to have a secondary cause of hypertension (such as renovascular hypertension) after careful evaluation. On the other hand, those patients with hypertensive urgencies as defined previously can be treated in the emergency room or outpatient department and can avoid hospital admission. Careful, immediate, and routine follow-up is important in these patients.     

Hypertension in the intensive care unit

PURPOSE OF REVIEW: The severity of hypertensive crises is determined by the presence of target organ damage rather than the level of blood pressure. Hypertensive urgencies with no signs of organ dysfunction can therefore be distinguished from hypertensive emergencies in which the presence of severe end-organ damage requires prompt therapy. Hypertensive emergencies include acute aortic dissection, hypertensive encephalopathy, acute myocardial ischaemia, severe pulmonary oedema, eclampsia, and acute renal failure. RECENT DEVELOPMENTS: Malignant hypertension is a severe form of hypertensive emergency demanding special consideration because of the risks of permanent blindness and renal failure. Catecholamine excess and postoperative hypertension may also sometimes require urgent treatment. The management of patients with hypertensive emergencies must be ensured in an intensive care unit, and must include the parenteral administration of antihypertensive drugs and accurate blood pressure monitoring. SUMMARY: Except for acute aortic dissection, the recommended goals of treatment are a reduction of mean arterial pressure by no more than 20% during the first few hours, because an abrupt fall in blood pressure in patients with preexisting hypertension may induce severe ischaemic injury in major organs as a result of the chronic adaptation of autoregulation mechanisms. Hypertension in the context of acute stroke should be treated only rarely and cautiously because of the presence of impaired autoregulation.     

Differentiation and investigation of primary versus secondary hypertension (Cushing reflex)

Hypertensive encephalopathy is a rare complication of severe or malignant hypertension. When treated promptly it is potentially reversible without leaving long-term neurologic damage. It can be difficult to differentiate from cerebrovascular accidents or uremia. Acute elevations of intracranial pressure cause acute elevations of blood pressure--the Cushing reflex. This association is less clear for chronic elevations of intracranial pressure, which could occur with tumors. In patients with hypertensive encephalopathy, there are usually diffuse neurologic signs, evidence of visual upset, variable alterations in conscious level, and often a history of rather gradual onset and more systemic symptoms beforehand. The optic fundi show the characteristic hemorrhages, exudates and papilledema, while the urine usually contains protein red cells and casts. Early treatment is mandatory but need not be by the parenteral route, and any blood pressure reduction should be gradual. Vigorous antihypertensive therapy under such circumstances can lead to problems with relative hypotension and underperfusion of vital organs such as the brain, the heart and the kidneys.     

Clinical features in the management of selected hypertensive emergencies

A hypertensive emergency is a clinical diagnosis that is appropriate when marked hypertension is associated with acute target-organ damage; in this setting, lowering of blood pressure (BP) is typically begun within hours of diagnosis. For hypertensive urgency with no acute target-organ damage, BP lowering may occur over hours to days. A hypertensive emergency may present with cardiac, renal, neurologic, hemorrhagic, or obstetric manifestations, but prompt recognition of the condition and institution of rapidly acting parenteral therapy to lower BP (typically in an intensive care unit) are widely recommended. For aortic dissection, the systolic BP target is lower than 120 mm Hg, to be achieved during the first 20 minutes using a beta-blocker (typically esmolol) and a vasodilator to reduce both shear stress on the aortic tear and the BP, respectively. Otherwise, sodium nitroprusside is the agent with the lowest acquisition cost and longest record of successful use in hypertensive emergencies; however, it is metabolized to toxic thiocyanate and cyanide. Other attractive agents include fenoldopam mesylate, nicardipine, and labetalol; in pregnant women, magnesium and nifedipine are used commonly. Most authors suggest a reduction in mean arterial pressure of approximately 10% during the first hour and a further 10% to 15% during the next 2 to 4 hours; hypoperfusion can result if the BP is lowered too suddenly or too far (eg, into the range of <140/90 mm Hg). Oral antihypertensive therapy can usually be instituted after 6 to 12 hours of parenteral therapy, and the patient moved out of the intensive care unit, when consideration should be given to screening for secondary causes of hypertension. Long-term follow-up to ensure adequate control of hypertension is necessary to prevent further target-organ damage and recurrence of another hypertensive emergency.     

Geriatric hypertension: antihypertensive therapy in coronary artery disease

Systemic hypertension is a common clinical problem in the elderly. There is emerging evidence to suggest that with careful utilization of antihypertensive drugs, blood pressure can be lowered in the elderly population. Whether isolated systolic hypertension should be treated aggressively remains an unanswered question despite the evidence that systolic hypertension can cause certain cardiovascular complications. An elderly patient with hypertension and concomitant coronary artery disease merits proper blood pressure control with appropriate drugs to prevent progression of coronary disease. The therapeutic objective is not only to lower the blood pressure but to accomplish this goal with drugs which are likely to have a favorable effect on coronary artery disease. Changing trends in the drug therapy of hypertension indicate that calcium antagonists and beta-blocking drugs offer a therapeutic advantage in elderly hypertensive patients with coronary artery diseases.     

Hypertensive crisis: hypertensive emergencies and urgencies

Hypertensive crisis is a serious condition that is associated with end-organ damage or may result in end-organ damage if left untreated. Causes of acute rises in blood pressure include medications,noncompliance, and poorly controlled chronic hypertension. Treatment of a hypertensive crisis should be tailored to each individual based on the extent of end-organ injury and comorbid conditions. Prompt and rapid reduction of blood pressure under continuous surveillance is essential in patients who have acute end-organ damage.     

Leitliniengerechte Differenzialtherapie der Hypertonie

The goal of antihypertensive therapy is to lower blood pressure and, by doing so, to decrease cardiovascular risk. Life style changes and drugs are available for the treatment of hypertensive patients. In order to reach the target blood pressure, most patients with hypertension need drug treatment in addition to life style changes. In all hypertensive patients, the target blood pressure is <140/90 mmHg. In patients with diabetes mellitus, with chronic renal failure as well as in patients with complications of hypertension and, thereby a very high cardiovascular risk, the target blood pressure is <130/80 mmHg. Diuretics, beta-blockers, calcium antagonists, ACE-inhibitors and angiotensin receptor blockers are the drugs of first choice in the treatment of hypertension. The selection among these drug classes has to consider probable side effects as well as accompanying diseases and complications of hypertension. One should also take into account that most of the beneficial effects of antihypertensive therapy is due to the decrease of blood pressure per se and that the majority of hypertensive patients require the combination of two or more antihypertensive drugs in order to reach the target blood pressure.     

Management of hypertensive crises: the scientific basis for treatment decisions

The spectrum of disorders associated with an elevated blood pressure (BP) encompasses chronic uncomplicated hypertension and the hypertensive crises, including hypertensive urgencies and emergencies. Although these syndromes vary widely in their presentations, clinical courses, and outcomes they share pathophysiologic mechanisms and, consequently, therapeutic responses to specifically targeted antihypertensive drug types. Nevertheless, hypertensive crises are often treated with drugs which, in that setting are either unsafe or are of unsubstantiated efficacy. The purpose of this review is to examine the pathophysiology of commonly encountered hypertensive crises, including stroke, hypertensive encephalopathy, aortic dissection, acute pulmonary edema, and preeclampsia-eclampsia and to provide a rational approach to their treatment based upon relevant pathophysiologic and pharmacologic principles. Measurement of plasma renin activity (PRA) level often provides insight regarding pathophysiology and predicts efficacy of antihypertensive treatments in the individual patient. However, in hypertensive crises, drug therapy is initiated before the PRA level is known. Nevertheless, the renin-angiotensin dependence (R-type) or volume dependence (V-type) of hypertension can often be deduced by the BP response to drugs that interrupt the renin system (R-drugs) or that decrease body volume (V-drugs). Based upon these considerations, a treatment algorithm is provided to guide drug selection in patients presenting with a hypertensive crisis.     

Circulating atrial natriuretic polypeptide in essential hypertension

To investigate the significance of atrial natriuretic polypeptide (ANP) in essential hypertension, we measured plasma ANP concentrations in 43 subjects with essential hypertension uncomplicated by cardiac or renal failure, in 16 subjects with borderline hypertension, and in 17 normotensive control subjects. Plasma ANP levels were significantly higher in hypertensive subjects compared to borderline hypertensive subjects (p less than 0.05) and normotensive control subjects (p less than 0.05). Hypertensive subjects with left ventricular hypertrophy (LVH) had higher plasma ANP levels than the hypertensive group as a whole (p less than 0.05). A significant positive correlation was observed between mean blood pressure and plasma ANP level in the hypertensive group (n = 43, gamma = 0.77, p less than 0.01). Furthermore, plasma ANP level was decreased significantly after 4 weeks of effective antihypertensive therapy compared with the initial value (p less than 0.05). These results suggest that plasma ANP is frequently elevated in hypertensive subjects with markedly high blood pressure or LVH, and it can be reduced by effective therapy with antihypertensive drugs.     

Hypertension in the Elderly

Hypertension as a risk factor for cardiac and cerebrovascular morbidity and mortality poses a major health problem for our increasingly elderly population. Recent trials have shown large reductions in stroke, heart failure, and coronary artery disease when elderly hypertensive patients are treated. These benefits are also seen in elderly patients with isolated systolic hypertension. The elderly patient with hypertension should be investigated and managed in a similar manner to their younger counterpart. Nonpharmacological measures, such as dietary salt and calorie restriction, regular exercise, cessation of smoking, and reduction of excess alcohol intake, should be recommended. If these are insufficient, pharmacological treatment should be tailored to the individual patient. Diuretics have been shown to improve outcome measures in the elderly. Other antihypertensive drugs may be added or substituted depending on the patient's blood pressure response to therapy and their comorbid conditions. If all elderly hypertensive patients were treated, a major reduction in cardiovascular and cerebrovascular mortality and morbidity would result. Consideration also needs to be given to nonpharmacological treatment, particularly salt restriction in older subjects where blood pressure is at the upper limit of normal, as this would also result in a major reduction in cardiovascular morbidity and mortality.     

A new cause of resistant arterial hypertension: coprescription with anticonvulsant treatments]

This article provides two case reports about pharmacokinetic interactions with hypertensive drug therapy and anticonvulsive treatment. First, a 49-year-old patient presenting severe hypertension had a non-traumatic cerebral hemorrhage with convulsions. Extensive etiologic investigations did not find any cause of secondary hypertension. Under an association of four antihypertensive drugs regimen, associated with carbamazepine blood pressure was not controlled. Finally, blood pressure was well controlled after replacement of carbamazepine with vigabatrin. The second case reports a 64-year-old treatment-resistant essential hypertensive patient, carbamazepine was associated with antihypertensive treatment because of aggressivity attributed to Alzheimer's disease. After withdrawal of carbamazepine treatment, blood pressure reached normal values with the same antihypertensive regimen. Those case reports suggest drug-drug interactions between antihypertensive and anticonvulsive drug therapies. Following explanation can be hypothesis: several antihypertensive drugs are liver-metabolised by microsomal cytochrome P450 3A4 isoform that could explain a significantly decreased half-life in association with enzymatic inducers, such as rifampicine or antiepileptic drugs (phenobarbital, phenytoin or carbamazepine). CONCLUSION: When blood pressure is not controlled without cause of secondary hypertension, physicians must be careful with drug-drug interactions.     

Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evaluation and treatment

Hypertension is a very common modifiable risk factor for cardiovascular morbidity and mortality. Patients with hypertension represent a diverse group. In addition to those with primary hypertension, there are patients whose hypertension is attributable to secondary causes, those with resistant hypertension, and patients who present with a hypertensive crisis. Secondary causes of hypertension account for less than 10% of cases of elevated blood pressure (BP), and screening for these causes is warranted if clinically indicated. Patients with resistant hypertension, whose BP remains uncontrolled in spite of use of 3 or more antihypertensive agents, are at increased cardiovascular risk compared with the general hypertensive population. After potentially correctible causes of uncontrolled BP (pseudoresistance, secondary causes, and intake of interfering substances) are eliminated, patients with true resistant hypertension are managed by encouraging therapeutic lifestyle changes and optimizing the antihypertensive regimen, whereby the clinician ensures that the medications are prescribed at optimal doses using drugs with complementary mechanisms of action, while adding an appropriate diuretic if there are no contraindications. Mineralocorticoid receptor antagonists are formidable add-on agents to the antihypertensive regimen, usually as a fourth drug, and are effective in reducing BP even in patients without biochemical evidence of aldosterone excess. In the setting of a hypertensive crisis, the BP has to be reduced within hours in the case of a hypertensive emergency (elevated BP with evidence of target organ damage) using parenteral agents, and within a few days if there is hypertensive urgency, using oral antihypertensive agents.