Dutch guideline for the management of hypertensive crisis -- 2010 revision

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.     

Accelerated arterial hypertension in a young male

Hypertensive crises are situations when arterial hypertension shows its immediate damaging potential, and in such circumstance, antihypertensive therapy provides its life-saving effectiveness. Among these situations are hypertensive emergencies, hypertensive urgencies, hypertensive encephalopathy, and also accelerated-malignant hypertension characterised by the presence of grade 3 or grade 4 Keith-Wagener retinopathy and numerous complications (acute renal failure, heart failure, haemorrhagic brain stroke or acute coronary events). Despite of antihypertensive therapy, the mortality rate of accelerated-malignant hypertension is about 25% after the 5th year. We present the case of a thirty-three years old male, with a five-year history of non-treated hypertension, who develops accelerated- hypertension with heart failure, microangiopathic haemolytic anaemia and renal failure that requires renal replacement therapy. After a strict control of blood pressure; initially using parenteral agents such as Solinitrin and Urapidil, followed by angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers, calcium channel blockers and Hydralazine, the patient partially recovers his renal function, resulting in the withdrawal of haemodialysis.     

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.     

Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature

BACKGROUND: Hypertensive urgencies and emergencies are common clinical occurrences in hypertensive patients. Treatment practices vary considerably to because of the lack of evidence supporting the use of one therapeutic agent over another. This paper was designed to review the evidence for various pharmacotherapeutic regimens in the management of hypertensive urgencies and emergencies, in terms of the agents' abilities to reach predetermined "safe" goal blood pressures (BPs), and to prevent adverse events. METHODS: medline was searched from 1966 to 2001, and the reference lists of all the articles were retrieved and searched for relevant references, and experts in the field were contacted to identify other relevant studies. The Cochrane Library was also searched. Studies that were eligible for inclusion in this review were systematic reviews of randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research. No language restrictions were used. RESULTS: None of the trials included in this review identified an optimal rate of BP lowering in hypertensive emergencies and urgencies. The definitions of hypertensive emergencies and urgencies were not consistent, but emergencies always involved target end-organ damage, and urgencies were without such damage. Measures of outcome were not uniform between studies. The 4 hypertensive emergency and 15 hypertensive urgency studies represented 236 and 1,074 patients, respectively. The evidence indicated a nonsignificant trend toward increased efficacy with urapidil compared to nitroprusside for hypertensive emergencies (number needed to treat [NNT] for urapidil to achieve target BP, 12; 95% confidence interval [95% CI], number of patients needed to harm [NNH], 5 to NNT, 40 compared to nitroprusside). Several medications were efficacious in treating hypertensive urgencies, including: nicardipine (NNT for nicardipine compared to plabebo, 2 in one study [95% CI, 1 to 5] and 1 in another [95% CI, 1 to 1]); lacidipine (NNT, 2; 95% CI, 1 to 8 for lacidipine vs nifedipine) or urapidil (NNT for urapidil compared to enalaprilat and nifedipine, 4; 95% CI, 3 to 6); and nitroprusside and fenoldopam (all patients reached target BP in 2 studies). The studies reported 2 cases of cerebral ischemia secondary to nifedipine. CONCLUSIONS: Many effective agents exist for the treatment of hypertensive crises. Because of the lack of large randomized controlled trials, many questions remain unanswered, such as follow-up times and whether any of the studied agents have mortality benefit.     

The diagnosis and management of hypertensive crises

Severe hypertension is a common clinical problem in the United States, encountered in various clinical settings. Although various terms have been applied to severe hypertension, such as hypertensive crises, emergencies, or urgencies, they are all characterized by acute elevations in BP that may be associated with end-organ damage (hypertensive crisis). The immediate reduction of BP is only required in patients with acute end-organ damage. Hypertension associated with cerebral infarction or intracerebral hemorrhage only rarely requires treatment. While nitroprusside is commonly used to treat severe hypertension, it is an extremely toxic drug that should only be used in rare circumstances. Furthermore, the short-acting calcium channel blocker nifedipine is associated with significant morbidity and should be avoided. Today, a wide range of pharmacologic alternatives are available to the practitioner to control severe hypertension. This article reviews some of the current concepts and common misconceptions in the management of patients with acutely elevated BP.     

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.     

Hypertensive crises: classification and current management

Data of current literature concerning with hypertensive emergencys and urgencies is presented. Hypertensive emergencys is a heterogeneous group of clinical states, caused or complicated by arterial hypertension, that require prompt blood pressure lowering to reduce morbidity and preserve life. The currently available choices for parenteral therapy of hypertensive emergencies and for oral therapy of hypertensive urgencies in selected groups of patients are extensively reviewed.     

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.     

Strategies for managing perioperative hypertension

Acute perioperative hypertension is associated with a higher risk of perioperative myocardial ischemia, bleeding, stroke, and renal failure. The immediate concern of short-term antihypertensive therapy is to prevent excessive surgical bleeding from arterial anastomoses, myocardial ischemia, and neurologic complications while causing minimal adverse effects until oral therapy can be resumed. This article reviews perioperative hypertension emergencies/urgencies and various approaches for management.     

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.     

Treatment of hypertensive urgencies and emergencies with nifedipine

The calcium channel blocker, nifedipine, is an effective antihypertensive agent for the treatment of hypertensive urgencies and emergencies. It produces a prompt, safe, predictable, and consistent reduction in systemic arterial pressure with minimal adverse effects. The reduction in blood pressure is inversely correlated with the pretreatment blood pressure level. Various nonparenteral administration forms (oral, sublingual, buccal, and rectal) permit a versatile, noninvasive, cost-effective alternative to parenteral antihypertensive therapy and continuous hemodynamic monitoring. The overall efficacy in reaching goal blood pressure approaches 98% with a 10 to 20 mg dose of nifedipine. Hemodynamic changes are favorable, and there is rarely any associated morbidity (severe hypotension) or mortality. The role of nifedipine in the treatment of hypertensive emergencies is promising, but further studies are needed to compare it to other approved emergency antihypertensive regimens.     

Choice of drug treatment for obesity-related hypertension: where is the evidence?

Hypertension and obesity are common medical conditions independently associated with increased cardiovascular risk. Many large epidemiological studies have demonstrated associations between body mass index and blood pressure, and there is evidence to suggest that obesity is a causal factor in the development of hypertension in obese individuals. Consequently, all hypertension management guidelines consider weight reduction as a first step in the management of increased blood pressure in obese individuals. Weight reduction may be achieved by behaviour modification, diet and exercise, or by the use of anti-obesity medications. However, the long-term outcomes of weight management programmes for obesity are generally poor, and most hypertensive patients will require antihypertensive drug treatment. Some classes of antihypertensive agents may have potentially unwanted effects on some of the metabolic and haemodynamic abnormalities that link obesity and hypertension, yet most hypertension guidelines fail to provide specific advice on the pharmacological management of obese patients. This may be because there are currently no studies examining the efficacy of specific antihypertensive agents in reducing mortality in obese hypertensive patients. This paper reviews the theoretical reasons for the differential use of the major classes of antihypertensive agents in the pharmacological management of obesity-related hypertension and also considers the potential role of anti-obesity agents.     

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.     

Blood pressure management and guideline adherence in hypertensive emergencies and urgencies: A comparison between telemedically supported and conventional out‐of‐hospital care

Prehospital hypertensive emergencies and urgencies are common, but evidence is lacking. Telemedically supported hypertensive emergencies and urgencies were prospectively collected (April 2014–March 2015) and compared retrospectively with a historical control group of on‐scene physician care in the emergency medical service of Aachen, Germany. Blood pressure management and guideline adherence were evaluated. Telemedical (n=159) vs conventional (n=172) cases: blood pressure reductions of 35±24 mm Hg vs 44±23 mm Hg revealed a group effect adjusted for baseline differences (P=.0006). Blood pressure management in categories: no reduction 6 vs 0 (P=.0121); reduction ≤25% (recommended range) 113 vs 110 patients (P=.2356); reduction >25% to 30% 13 vs 29 (0.020); reduction >30% 12 vs 16 patients (P=.5608). The telemedical approach led to less pronounced blood pressure reductions and a tendency to improved guideline adherence. Telemedically guided antihypertensive care may be an alternative to conventional care especially for potentially underserved areas.     

Hospital and out‐of‐hospital mortality in 670 hypertensive emergencies and urgencies

Long‐term mortality in patients with acute severe hypertension is unclear. The authors aimed to compare short‐term (hospital) and long‐term (12 months) mortality in these patients. A total of 670 adults presenting for acute severe hypertension between January 1, 2015, and December 31, 2015, were included. A total of 57.5% were hypertensive emergencies and 66.1% were hospitalized: 98% and 23.2% of those with hypertensive emergencies and urgencies, respectively (P = .001). Hospital mortality was 7.9% and was significantly higher for hypertensive emergencies (12.5% vs 1.8%, P = .001). At 12 months, 106 patients died (29.4%), mainly from hypertensive emergencies (38.9% vs 8.9%, P = .001). Median survival was 14 days for neurovascular emergencies and 50 days for cardiovascular emergencies. Patients with hypertensive emergencies or urgencies had bad long‐term prognosis. Short‐term mortality is mainly caused by neurovascular emergencies, but cardiovascular emergencies are severe, with high mortality at 12 months. These results justify better follow‐up and treatment for these patients.     

Hypertensive emergencies

Critical cases of high blood pressure are common clinical occurrences that may account for as many as 25% of all medical emergencies. About 75% of these increases in blood pressure can be judged as hypertensive urgencies, 25% are even hypertensive emergency situations. Nevertheless, only less than 1% of the hypertensive population experiences hypertensive urgency or emergency situations. Hypertensive emergencies are defined as acute cardiac, vascular or cerebral target organ damages. In these cases an acute lowering of blood pressure is inevitable. The rate and intensity of blood pressure depression is dependent on the localization of organ damages. For cardiac and vascular damages it is absolutely necessary to lower the blood pressure rapidly to near normal values. On the contrary, cerebral organ damages are better treated by a moderate lowering of blood pressure peaks to slightly increased blood pressure levels. In hypertensive urgencies no target organ damages occur. For these patients a slow lowering of blood pressure values to normal levels is adequate.     

Patients With Hypertensive Crises Who Are Admitted to a Coronary Care Unit: Clinical Characteristics and Outcomes

Patients with hypertensive crises, especially hypertensive emergencies, require immediate admittance to an intensive care unit for rapid blood pressure (BP) control. The authors analyzed the prevalence of hypertensive crisis, the clinical characteristics, and the evolution of patients with hypertensive emergencies and urgencies. Patients were divided into 3 groups according to their BP values: group I, predominant systolic hypertension (≥180/≤119 mm Hg); group II, severe systolic and diastolic hypertension (≥180/≥120 mm Hg); and group III, predominant diastolic hypertension (≤179/≥120 mm Hg). Of all of the patients admitted to a coronary care unit, 538 experienced a hypertensive crisis, which represented 5.08% of all admissions. Hypertensive emergency was predominant in 76.6% of the cases, which corresponded to acute coronary syndrome and acute decompensated heart failure in 59.5% and 25.2% of the cases, respectively. A pattern of predominant systolic hypertension (≥180/≤119 mm Hg) was most commonly observed in the hypertensive crisis group (71.4%) and the hypertensive emergency group (72.1%). The medications that were most commonly used at onset included intravenous vasodilators (nitroglycerin in 63.4% and sodium nitroprusside in 16.4% of the patients). The overall mortality rate was 3.7%. The mortality rate was 4.6% for hypertensive emergency cases and 0.8% for hypertensive urgencies cases.     

Reversal of clonidine toxicity by naloxone

Clonidine is a centrally acting antihypertensive agent used in the management of essential hypertension. Oral clonidine loading is now used frequently in the management of hypertensive urgencies (ie, increases in arterial pressure not associated with acute, life-threatening end-organ injury). We report the case of a patient with an acute inferior myocardial infarction associated with blunt chest trauma who developed an abrupt and unexplained increase in arterial pressure 24 hours after admission and who was treated with oral clonidine (0.5 mg in divided doses over two hours). Drug therapy was followed by prolonged (four hours) systemic arterial hypotension (mean arterial pressure less than 70 mm Hg). Four milligrams of naloxone in two divided doses was given. Each naloxone bolus was followed by a 15-mm-Hg increase in mean arterial pressure and a return to values that were normal for this patient. Naloxone may be of value in reversing clonidine toxicity when clonidine is given to treat an acute rise in arterial pressure.     

Diagnosis and treatment of hypertensive crises in the elderly patients

Hypertension is a common clinical problem in the elderly worldwide and physicians of all types are likely to encounter patients with hypertensive urgencies and emergencies in these patients. Although various terms have been applied to these conditions, they are all characterized by acute elevations in blood pressure and evidence of end-organ injury. Prompt, but carefully considered therapy is necessary to limit morbidity and mortality. A wide range of pharmacologic alternatives are available to the practitioner to control blood pressure and treat complications in these patients. The management of the elderly patient with hypertensive crises needs to include close monitoring and a gentle decline in blood pressure to avoid catastrophic complications, exacerbation of ischemic myopathy, and vascular insufficiency.     

Treatment of hypertensive urgencies with oral nifedipine, nicardipine, and captopril

Sixty-five patients with uncomplicated hypertensive urgencies were treated in the emergency and cardiology departments with 20 mg nifedipine, 20 mg nicardipine, or 25 mg captopril in a randomized study. The study population consisted of 65 patients ranging in age from forty-one to seventy-one. Blood pressure and heart rate were assessed for six hours after intake of the antihypertensive agents. Within sixty minutes nifedipine reduced blood pressure by an average of 74.7 mmHg for the systolic and 35.4 mmHg for the diastolic. Average heart rate increased significantly by 11.6 beats/min at within thirty minutes. Nicardipine and captopril produced equivalent falls in systolic (-81.6 and -79.4 mmHg) and diastolic (-37.3 and -33 mmHg) blood pressure respectively, but did not increase heart rate significantly. The antihypertensive effect of each drug was maintained until six hours after medication. In conclusion, nifedipine, nicardipine, and captopril show similar efficacy in the treatment of hypertensive urgencies. The authors believe that these drugs can be used as first-line therapy in the treatment of hypertensive urgencies safely and effectively.