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.     

Hypertensive emergencies in diabetic patients from predominantly African American urban communities

Aim: The aim of this study was to identify risk factors for hypertensive emergencies in diabetic patients presenting with severely elevated blood pressure.

Methods: Using electronic medical records, this study identified diabetic patients with hypertensive crisis who presented to the emergency department of Newark Beth Israel Medical Center, Newark, NJ from June 2013 to May 2016. Diabetic patients with hypertensive emergencies were compared with non-diabetic patients based on important demographic and clinical characteristics.

Results: Patients with diabetes accounted for 52.27% of all hypertensive emergencies during the study period. There were 264 diabetic patients with hypertensive emergencies and 519 diabetic patients with hypertensive urgencies. The majority of patients were African Americans (88.6%). The odds of hypertensive emergencies were strikingly higher in diabetic patients with hyperlipidemia (OR 1.66, 95% CI 1.23–2.24), coronary artery disease (OR 2.95, 95% CI 2.15–4.05), congestive heart failure (OR 6.28, 95% CI 4.49–8.80), renal insufficiency (OR 2.84, 95% CI 2.10–3.86) and low hemoglobin (OR 0.9, 95% CI 0.84–0.97). Acute or worsening heart failure was the most frequent acute target organ injury (49.6%) followed by non-ST elevation myocardial infarction (41.7%). Diabetic and non-diabetic patients had similar rates of target organ injuries.

Conclusion: The development of hypertensive emergencies in patients with diabetes was not because of diabetes per se but because of coexisting highly elevated blood pressure. Tight blood pressure control may decrease the risk of hypertensive emergencies in this patient population.     

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.     

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 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.     

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.     

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.     

乌拉地尔与卡托普利治疗高血压急症的疗效观察

目的：探讨乌拉地尔与卡托普利治疗高血压急症的临床效果。方法：将2009年1月--2010年1月间在我院治疗的高血压急症患者60例随机分为观察组和对照组,对照组给予舌下含服卡托普利治疗,观察组给予乌拉地尔静脉应用。结果：治疗后两组患者各时间点SBP、DBP及HR与对照组分别比较差异无统计学意义（P〉0．05）。观察纽总有效率为96．67％,对照组为93．33％,两组比较差畀具有统计学意义（P〈0．05）。两组患者均未见明显的药物不良反应。结论：乌拉地尔与卡托普利治疗高血压急症的临床效果肯定,均可选用。     

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.     

Single-dose sublingual nifedipine as the only treatment in hypertensive urgencies and emergencies

One hundred and eighteen patients with hypertensive urgencies and emergencies and diastolic blood pressure (DBP) at least 120 mm Hg by the cuff method were seen at the Emergency Care Department; none had received calcium channel blockers during the previous twelve hours. Patients with DBP of 120 to 139 mm Hg received 10 mg of sublingual nifedipine; patients with left ventricular hypertrophy or failure, renal disease, hypertensive encephalopathy, angina, papilledema, or a DBP over 140 mm Hg received 20 mg of the drug. The criterion for control was the achievement of a DBP of 100 mm Hg or less within sixty minutes of receiving sublingual nifedipine and maintenance of the effect until discharge. Control was achieved in all patients; a sixty-three-year-old man died of a brain hemorrhage after pulmonary edema and a DBP of 210 had been controlled; the other 117 were discharged to their attending physicians, either as outpatients or to a hospital ward. No patient developed hypotension, clinical or electrocardiographic signs of myocardial ischemia, or clinical signs of neurologic dysfunction. Practical, fast, safe, and dependable control of hypertensive urgencies and emergencies has made sublingual nifedipine the treatment of choice of such patients in the Emergency Care Department.     

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.     

乌拉地尔治疗高血压急症的疗效和安全性研究

目的：观察乌拉地尔、硝普钠治疗高血压急症的降压效果及安全性。方法：86例高血压急症患者被随机分成：乌拉地尔组（43例）,持续静脉泵人乌拉地尔;硝普钠组（43例）,持续静脉泵人硝普钠作为对照。监测两组血压,观察治疗效果,同时了解达到治疗高血压急症的最初目标的安全性。结果：乌拉地尔、硝普钠组在用药前血压无显著差异[（219．21±27．92）／（148．79±14．15）mmHg比（226．98±23．00）／（148．03±11．49）mmHg,P〉0．05];两组在用药5min后血压开始明显下降,用药后各时间段血压均较治疗前明显下降,（P〈0．01）,于用药后360min乌拉地尔、硝普钠组血压分别降至[（143．53±11．16）／（89．56±8．01）mmHg]、[（143．88±8．09）mmHg／（90．16±6．44）mmHg],两种药物疗效差异无显著性（P〉0．05）,都能达到治疗的最初目标。乌拉地尔、硝普钠组用药前心率无显著差异[（98．28±11．52）次／min比（98．09±9．23）次／mini,于用药后360min乌拉地尔组心率显著降至（96．95±11．37）次／min,而硝普钠组心率却显著上升至（100．33±10．96）次／min,乌拉地尔组对心率影响显著优于硝普钠组（P〈O．05）。结论：乌拉地尔对高血压急症有显著疗效,安全性高,值得推广。     

Double-Blind,randomized comparative study of the antihypertensive effect of nicardipine slow-release and nifedipine slow-release in hypertensive patients with coronary heart disease

The main aim of this study was to investigate whether a new slow-release formation of nicardipine can control hypertension and whether its antihypertensive effect is manifest throughout the dose intervals. In a randomized, double-blind placebo-controlled study, the antihypertensive effect of two calcium antagonists (Type II) was investigated in two independent groups of hypertensive patients with coronary artery disease. One group of patients received 40 mg nicardipine slow-release b.i.d. and the other 20 mg nifedipine slow-release b.i.d. The effect of the active drugs on blood pressure (BP), heart rate, and hemodynamics was compared with placebo within each group. In addition, a group comparison was made to establish whether nicardipine had any advantage over nifedipine. Twenty-eight patients [27 female, 1 male; 55 (41-72) years old], 18 with previous myocardial infarction (MI) entered the study (nicardipine, 15 patients; nifedipine, 13 patients). A placebo period of 3 days was followed by a 13-day drug treatment period. From the first to last trial day, BP and heart rate were measured three times daily. At the end of the placebo and the active drug periods, the following measurements were carried out: ambulatory BP monitoring by half-hourly recording for 12.5 hours with the Remler system, ergometric tests with ECG, and right heart catheterization. Both drugs lowered the BP at rest, during exercise, and during usual daily activities. The antihypertensive effect of nicardipine was significant for the daytime mean arterial BP (MAP) and for systolic BP and diastolic BP at various stages of the exercise tests. The difference between the effect of nicardipine and nifedipine was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

乌拉地尔和尼卡地平对老年高血压急症的疗效及安全性比较

目的探讨乌拉地尔和尼卡地平治疗老年高血压急症的疗效和不良反应。方法老年高血压急症患者39例,随机分为乌拉地尔组22例和尼卡地平组17例,分别给予乌拉地尔和尼卡地平降压,记录2组治疗前及治疗后5、10、15、20、25、30、60min、2h及离院时收缩压、舒张压、平均动脉压(MAP)和心率及不良反应。结果 2组治疗前后收缩压、舒张压、MAP和心率比较,差异无统计学意义(P>0.05);2组治疗前后不同时间点收缩压与治疗前收缩压差值比较,差异无统计学意义(P>0.05);2组治疗后2h舒张压和MAP与治疗前差值比较,差异有统计学意义(P<0.05,P<0.01),乌拉地尔组下降更加明显(P<0.01)。结论乌拉地尔和尼卡地平对老年高血压急症症状的缓解及对收缩压降压效果相当;乌拉地尔起效更快且有进一步使舒张压和MAP降低的趋势;2组均可使心率下降,尼卡地平治疗早期患者心率可一过性上升,但并不显著增加心率;2种药物安全性均较好。     

Antihypertensive therapy with nicardipine for patients with aortic disease is associated with more esmolol usage than urapidil

Background

Acute aortic disease is a common but challenging entity in clinical practice. Titration the blood pressure and heart rate to a target level is of paramount importance in the acute phase regardless of whether the patient will undergo a surgery or not eventually. In addition to the initially intravenous β-blockers, parenteral infusion of nicardipine and urapidil are the most common used antihypertensive therapy currently in mainland China. However, few empirical data was available with respect to the different effect on patients’ outcome of the two antihypertensive strategies. Specifically given the deleterious reflex tachycardia of vasodilators which may increase force of ventricular contraction and potentially worsen aortic disease. Therefore, this study was aimed to evaluate the difference of the abovementioned two antihypertensive strategies on the outcome of patients with aortic disease.

Methods

All patients with new diagnosed aortic diseases presented to our hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed. The antihypertensive strategies and their association with patients’ outcomes were evaluated with logistics regression.

Results

A total of 120 patients with new diagnosed aortic disease were included in the study. Of them, 47 patients received urapidil while 73 patients received nicardipine antihypertensive therapy. Patients with nicardipine were more quickly to reach the target blood pressure level than those treated with urapidil (median, 18 vs. 35 min, P=0.024). After adjustment for patient demographics, co-morbidity, involved extend of aorta, interventional strategies, antihypertensive therapy with nicardipine (with urapidil as reference) for patients with aortic disease was significantly associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval (CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI, 1.5-10.3, P=0.006). However, there was no significant correlation between nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123).

Conclusions

Although nicardipine achieved the target blood pressure level more quickly than urapidil for patients with aortic disease, it was associated with more esmolol use and longer ICU LOS.     

The haemodynamic effects of intravenous nifedipine in normotensive and hypertensive subjects

The antihypertensive effects of intravenous nifedipine, given by bolus and 2 hour infusion, were studied at two dose levels in seven hypertensive (mean BP 178/114 mmHg) and five age-matched normotensive controls (mean BP 128/81 mmHg). Nifedipine significantly reduced systolic and diastolic blood pressure in the hypertensive patients by approximately 20%, but not in the normotensive controls. Similar changes in heart rate and forearm blood flow were seen after bolus injection in both groups, but these were not sustained during infusion. Intravenous nifedipine may be a useful acute treatment for hypertensive emergencies.     

Comprehensive management of hypertensive emergencies and urgencies

Despite advances in chronic hypertension management, hypertensive emergencies and urgencies remain as serious complications. Much of this relates to poor compliance with effective antihypertensive management. Hypertensive emergencies and urgencies can also be seen as the initial manifestations of hypertension in pregnancy and in the perioperative period. Multiple classes of intravenous antihypertensive drugs are available to treat hypertensive emergencies, and specific agents may have an advantage in a given clinical situation. Orally active agents are used to treat hypertensive urgencies, and include clonidine, angiotensin-converting enzyme inhibitors, and labetalol. Most patients respond to drug therapy, but problems may arise related to a rapid normalization of blood pressure.     

Intravenous nicardipine in severe systemic hypertension

Sixty-six patients with severe hypertension were treated with intravenous nicardipine in 3 separate protocols. Each protocol had a common end point: Diastolic blood pressure would either reduce 25 mm Hg or measure below 95 mm Hg. Each of the 66 patients studied attained the desired clinical response end point. Intravenous nicardipine produced a gradual reduction in blood pressure, was effective in maintaining blood pressure control during constant infusion and had few undesirable effects. These observations suggest that intravenous nicardipine maybe a useful addition to a limited number of therapeutic agents currently available to the physician for treatment of hypertensive urgencies.     

Chronotherapy of Hypertension with Angiotensin Receptor Blockers–A Meta-Analysis of Blood Pressure Measured by Ambulatory Blood Pressure Monitoring in Randomized Trials

BackgroundWe performed this meta-analysis evaluating the efficacy of chronotherapy of hypertension with angiotensin receptor blockers (ARBs).MethodsWe searched Pubmed, Web of Science, and Cochrane for all published randomized trials that compare antihypertensive effects of ARBs between bedtime dosing and awakening dosing. Blood pressure (BP) was measured by ambulatory BP monitoring in patients with mild or moderate essential hypertension.ResultsThe effects of ARBs on BP were assessed in 805 essential hypertensive patients included in 8 trials with a follow-up of 12 ± 3 weeks. The sleep-time systolic and diastolic BP (SBP, DBP) with bedtime dosing greatly decreased as compared with awakening dosing (weighted mean differences [WMD] for SBP WMD ?5.23 [95% confidence intervals (CI), ?7.27, ?3.20] mm Hg, p < 0.001; WMD for DBP ?2.94 [95% CI, ?4.52, ?1.36] mm Hg, p < 0.001). The reduction of daytime SBP (WMD 0.98 [95% CI, ?0.20, 2.17] mm Hg, p = 0.10), DBP (WMD 0.11 [95% CI, ?0.68, 0.89] mm Hg, p = 0.79), 24 hour SBP (WMD ?0.75 [95% CI, ?1.93, 0.42] mm Hg, p = 0.21) and DBP (WMD ?0. 77 [95% CI, ?1.55 0.01] mm Hg, p = 0.05) with bedtime dosing was similar with awakening dosing.ConclusionsBedtime dosing with ARBs is more effective in lowering sleep-time BP than awakening dosing in patients with essential hypertension, suggesting a utilization of chronotherapy of hypertension with ARBs to reduce sleep-time high BP. Larger multi-ethnic studies are needed to investigate the efficacy of chronotherapy of hypertension.     

Different Definitions of Prevalent Hypertension Impact: The Clinical Epidemiology of Hypertension and Attainment of Healthy People Goals

Prevalent hypertension in National Health and Nutrition Examination Surveys (NHANES) is traditionally defined as blood pressure (BP) ≥140 mm Hg systolic and/or ≥90 diastolic and/or currently taking antihypertensive medications. When estimating prevalent hypertension, American Heart Association (AHA) statistical updates include the traditional definition of hypertension (tHTN) and untreated individuals with nonhypertensive BP told twice that they were hypertensive (nontraditional [ntHTN]). The characteristics of ntHTN and their impact on the clinical epidemiology of hypertension and Healthy People prevention and control goals are undefined. NHANES 1999–2002, 2003–2006, and 2007–2010 were analyzed. The ntHTN group was younger and had less diabetes and lower BP than the tHTN group but higher BP than the normotensive group. When classifying ntHTN as hypertensive, prevalent hypertension increased approximately 3% and control 5% to 6% across NHANES periods. In 2007–2010, the Healthy People 2010 goal of controlling BP in 50% of all hypertensive patientss was attained when ntHTN was classified as hypertension (56.5% [95% confidence interval (CI), 54.2–58.7]) and nonhypertension (51.8% [95% CI, 49.6–53.9]). When including ntHTN in prevalent hypertension estimates, the Healthy People 2020 goal of controlling BP in 60% of hypertensive patients becomes more attainable, whereas reducing prevalent hypertension to 26.9% (31.8% [95% CI, 30.5–33.1]) vs 28.7% [95% CI, 27.5–30.0]) becomes more challenging.