Idiopathic orthostatic hypotension (IOH) and sympathotonic orthostatic hypotension (SOH)]

IOH occurs as progressive autonomic failure (PAF) without any neurologic symptoms indicating multiple system atrophy or Parkinson's disease. The responsible lesion for IOH is yet obscure but has been suggested to be in the peripheral sympathetic nerves, since postganglionic sympathetic neurons in IOH fail to release norepinephrine and there present extensive supersensitivities to exogenous pressors. SOH is characterized as marked tachycardia induced by hypotensive stress like standing, and is less sensitive to the administered catecholamines. Careful examinations by some pharmacological studies are essential to diagnose IOH and SOH in patients with orthostatic hypotension.     

Droxidopa in neurogenic orthostatic hypotension

Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure (BP) on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy (MSA), pure autonomic failure (PAF), and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise BP by acting at the neurovascular junction to increase vascular tone. This article summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials.     

Hemodynamics in diabetic orthostatic hypotension.

Hemodynamic variables (blood pressure, cardiac output, heart rate, plasma volume, splanchnic blood flow, and peripheral subcutaneous blood flow) and plasma concentrations of norepinephrine, epinephrine, and renin were measured in the supine position and after 30 min of quiet standing. This was done in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously in the standing position in the diabetics with orthostatic hypotension, whereas moderate decreases were found in the other three groups. Upon standing, heart rate rose and cardiac output and plasma volume decreased similarly in the four groups. The increases in total peripheral resistance, splanchnic vascular resistance and subcutaneous vascular resistance were all significantly lower (P less than 0.025) in the patients with orthostatic hypotension compared with the other three groups. The increase in plasma norepinephrine concentrations in the patients with orthostatic hypotension was significantly lower (P less than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy.     

Evaluation and management of orthostatic hypotension

Orthostatic hypotension is defined as a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with blood pressure from the sitting or supine position. It results from an inadequate physiologic response to postural changes in blood pressure. Orthostatic hypotension may be acute or chronic, as well as symptomatic or asymptomatic. Common symptoms include dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache. Less common symptoms include syncope, dyspnea, chest pain, and neck and shoulder pain. Causes include dehydration or blood loss; disorders of the neurologic, cardiovascular, or endocrine systems; and several classes of medications. Evaluation of suspected orthostatic hypotension begins by identifying reversible causes and underlying associated medical conditions. Head-up tilt-table testing can aid in confirming a diagnosis of suspected orthostatic hypotension when standard orthostatic vital signs are nondiagnostic; it also can aid in assessing treatment response in patients with an autonomic disorder. Goals of treatment involve improving hypotension without excessive supine hypertension, relieving orthostatic symptoms, and improving standing time. Treatment includes correcting reversible causes and discontinuing responsible medications, when possible. Nonpharmacologic treatment should be offered to all patients. For patients who do not respond adequately to nonpharmacologic treatment, fludrocortisone, midodrine, and pyridostigmine are pharmacologic therapies proven to be beneficial.     

直立性低血压的年龄和性别差异

目的探讨直立性低血压(OH)的年龄和性别差异。方法 2001年1月至2010年4月在中南大学湘雅二医院晕厥专科门诊就诊或住院的不明原因晕厥或头晕患者1681例进行直立倾斜试验(HUTT)检查中符合OH诊断的患者73例,分为成人组(≥18岁)和儿童组(<18岁),分析其病程、诊断率、HUTT时3min血压变化的年龄和性别差异。结果 (1)病程及发病年龄:OH病程在成人组为0.23～552个月,平均(31.08±22.72)个月,儿童组为0.3～72个月,平均(12.69±18.32)个月,两组均表现为男性与女性比较无统计学差异[分别为(31.08±22.72)个月vs.(116.22±158.24)个月,t=2.049,P>0.05;(10.38±14.59)个月vs.(15.0±21.53)个月,t=0.814,P>0.05]。发病年龄在成人组为20～70岁,平均(45.96±14.81)岁,女性小于男性(t=6.828,P<0.05);儿童组为6～17岁,平均(10.47±2.40)岁,未见性别差异(t=1.411,P>0.05)。(2)诊断率及HUTT时3min内血压变化:OH诊断率在成年组(5.47%,...     

Management of orthostatic hypotension in the elderly

Orthostatic hypotension (OH) is a common health problem that affects 6% to 30% of the community-dwelling elderly. OH prevalence has been found to increase with age, influence the individual's quality of life, and be associated with increased rates of morbidity and mortality. Referencing evidence-based reports, the aim of the present article was to construct an OH management protocol for the elderly with OH. Causes of OH can be generally divided into recoverable and unrecoverable types. Recoverable types refer to OH conditions in which the patient's original health status can be restored following treatment. If such cannot be achieved, medical staffs must consider the possibility of an underlying unrecoverable factor. To treat unrecoverable OH, non-pharmacological intervention should be applied first. If such fails, then pharmacological interventions should be considered. Whether recoverable or unrecoverable, OH treatment should control acute health problems and follow general prevention principles. Nursing staffs play a crucial role in OH treatment. This proposed protocol may assist clinical nursing staffs to provide more appropriate elderly care.     

Adrenergic supersensitivity in Parkinsonians with orthostatic hypotension

The adrenergic status was studied through evaluation of platelet alpha 2-adrenoceptor number [( 3H]yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P less than 0.05) decreased from 144 +/- 9 and 76 +/- 6 mmHg in the lying position to 95 +/- 12 and 60 +/- 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 +/- 11 pg ml-1, (P less than 0.05) when compared with controls (219 +/- 13 pg ml-1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 +/- 14 pg ml-1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P less than 0.01) lower in Parkinsonians with orthostatic hypotension (0.19 +/- 0.03 microgram kg-1) when compared with Parkinsonians without orthostatic hypotension (0.86 +/- 0.11 microgram kg-1) or with controls (0.68 +/- 0.1 microgram kg-1). Platelet alpha 2-adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 +/- 52 fmol mg-1 protein) than in Parkinsonians without orthostatic hypotension (168 +/- 9 fmol mg-1 protein) or in controls (175 +/- 4 fmol mg-1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet alpha 2-adrenoceptor number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosing and treating neurogenic orthostatic hypotension in primary care

In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient’s risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension – for which the long-term prognosis in patients with NOH is yet to be established – must sometimes be balanced by the need to address a patient’s immediate risks.     

老年住院病人餐后低血压及体位性低血压的临床观察与护理

目的探讨住院老年病人餐后低血压（PPH）及体位性低血压（OH）的发生率及护理对策。方法应用无创心电监护仪测量78例老年病房住院治疗,病情相对平稳的老年病人进餐前后及早晨起床站立3min后血压。结果78例病人中57例出现PPH,餐后血压平均下降（37±6）mmHg,47例出现OH,站立后血压平均下降（41±5）mmHg,36例同时出现PPH及OH;74％的PPH病人出现症状,最常见为思睡及晕厥。有症状的OH占64％,头晕及跌倒危险最常见。结论PPH及OH在住院老年病人中常见,二者临床症状存在显著不同,危害较大,故对于老年住院病人进行健康教育,及时采取合理护理对策防止餐后血压下降及体位性低血压所致意外具有非常重要的意义。     

Aging and susceptibility to drug-induced orthostatic hypotension.

OBJECTIVE: To test the hypothesis that the short-term effect of transbuccal nitroglycerin (glyceryl trinitrate, 0.0625 to 1.5 mg) on orthostatic cardiovascular responses would predict the effect of a diuretic (5 mg bendroflumethiazide daily for 1 week), particularly in elderly subjects who may be at higher risk for orthostatic hypotension. METHODS: This was a randomized crossover study. Participants were 17 elderly (age range, 63 to 84 years) and 15 younger (age range, 19 to 35 years) healthy ambulant volunteers. Interventions and measures of outcome included blood pressure (BP; in millimeters of mercury) and heart rate (HR; in beats per minute) changes with standing, which were measured before administration of medication and after each drug treatment. RESULTS: Subjects in the elderly and younger groups had different BP and HR changes (mean percentage change) at 1 minute after standing in all three study phases (unmedicated, elderly: BP, -4%/+1%; HR, +12%; young: BP, +2%/+12%; HR, +27%; p = 0.06 for BP, p less than 0.01 for HR; bendroflumethiazide, elderly: BP, -9%/-3%; HR, +17%; young: BP, +1%/+11%; HR, +33%; p less than 0.05 for all; nitroglycerin (0.25 mg), elderly: BP, -15%/-12%; HR, +21%; young: BP, -6%/+7%; HR, +38%; p less than 0.05 for all). The incremental orthostatic effects of the two drugs were similar in the two age groups and were positively correlated (r = 0.65, p less than 0.001) in individual subjects. CONCLUSIONS: Individual susceptibility to drug-induced orthostatic hypotension depends on a combination of the age-related unmedicated orthostatic response and the additional drug effect, which is independent of age. The BP response to standing after administration of nitroglycerin may be useful in predicting the effect of other drugs known to influence orthostatic BP control.     

Afferent baroreflex dysfunction and age-related orthostatic hypotension.

1. To test the hypothesis that in apparently healthy elderly subjects with orthostatic hypotension there is afferent baroreflex dysfunction, cardiovascular and neurohumoral responses were measured after separate stimuli which activated baroreceptor (head-up tilt) and non-baroreceptor (cold stress, isometric exercise) afferent pathways. 2. In 15 healthy elderly control subjects blood pressure did not change with 60 degrees head-up tilting and there was a moderate increase in heart rate, whereas in 13 subjects with age-related orthostatic hypotension head-up tilting was associated with a marked fall in blood pressure but a similar heart rate response to that in the elderly control group. In contrast, both groups of subjects had similar blood pressure and heart rate responses to cold stress and sustained isometric exercise. 3. Nine subjects with autonomic neuropathy also showed a marked hypotensive response to head-up tilt, but produced no pressor response to cold stress or isometric exercise. 4. The plasma concentrations of noradrenaline, adrenaline and neuropeptide-Y-like immunoreactivity rose and that of atrial natriuretic peptide fell after head-up tilt in the study population as a whole. There were no significant differences between groups despite the much greater blood pressure drops in the subjects with autonomic neuropathy and in those with age-associated orthostatic hypotension. 5. The aorto-iliac pulse wave velocity index was significantly higher in subjects with age-associated orthostatic hypotension compared with that in control subjects. 6. The pattern of responses to the separate stresses observed in the group with age-associated orthostatic hypotension is characteristic and different from that in the elderly control subjects and the subjects with autonomic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

老年人直立性低血压变异性的调查

目的探讨老年人直立性低血压(OH)单日内、连续周间和相隔1年的变异性。方法对广东省佛山市某街道3所老人院居住者进行调查。直立性血压变化测量方法为患者平卧5 min后测量卧位血压,站立后测量1 min,3 min血压。以站立后1 min和(或)3 min测量的收缩压下降≥20 mm Hg和(或)舒张压下降≥10 mm Hg判断为OH。分别测量第1天早餐前、午餐前、午餐后、晚餐前以及第8天午餐前、第15天午餐前直立性血压变化,分析不同时间段OH的检出率以及符合OH标准不同次数患者的百分比。1年后随访复测午餐前直立性血压变化。结果共纳入162例老人院居民,站立后1 min收缩压变化值算术均数为-1.2 mm Hg,极差为120 mm Hg,四分位数间距为19 mm Hg,标准差为15.1 mm Hg,变异系数为-1 258.3%。第1天早餐前、午餐前、午餐后、晚餐前OH的检出率依次为16.7%、19.8%、11.7%、9.9%,差异有统计学意义(P=0.046)。第1天、第8天、第15天午餐前OH的检出率分别为19.8%、17.9%、16.7%(P=0.662)。同日4次测量符合1次、2次、3次、4次OH标准的患者依次有22.2%、9.3%、4.9%、0.6%。相隔1周3次午餐前测量符合1次、2次、3次OH标准的患者依次有19.1%、9.3%、5.6%。在第1天午餐前32例OH患者中,在第1天早餐前、午餐后、晚餐前以及第8天午餐前、第15天午餐前依次有37.5%、18.8%、18.8%、34.4%、46.9%再出现OH。持续性OH(6次测量有≥3次符合OH标准)患者站立后不适发生率较高。OH发生在站立后1 min的比例较3 min的高(14.1%vs.4.3%,P<0.01),站立后收缩压下降值达OH标准的比例较舒张压下降值达OH标准的比例高(10.8%vs.7.8%,P=0.01)。1年后复测午餐前OH检出率无差别,7.1%居民2次测量直立性血压变化均达到OH标准。结论单日内和连续周间、相隔1年个体OH存在显著的变异性,可重复性差。     

老年疗养员直立性低血压的预防

<正>高血压已引起广泛关注,但低血压往往不被了解而促使脑卒中的发生,成为间接危险。直立性低血压[1]的诊断主要依据为直立位较卧位时收缩压下降     

Plasma catecholamines and dopamine-beta-hydroxylase activity in chronic renal failure

Plasma and urinary catecholamines (CA) and plasma dopamine β-hydroxylase (DBH) activity were studied serially in 17 hypertensive patients with chronic renal failure (CRF) and in 15 age-matched patients with benign essential hypertension (EH). Resting levels of plasma epinephrine (E) plus norepinephrine (NE) in CRF patients were significantly greater than those in EH patients (P < 0.05), whereas plasma DBH activities in CRF patients tended to be lower than those in EH patients (P < 0.1). However, DBH activities were found to be similar for the two groups, when they were expressed in units per litre of blood instead of per litre of plasma. Urinary free E + NE and dopamine were significantly less in CRF than in EH, whereas no significant difference was noted in urinary excretion of conjugated E + NE and vanillylmandelic acid between the two groups. The ratio of conjugated E + NE/free E + NE and of vanillylmandelic acid/free E + NE were significantly greater in CRF than in EH patients (P < 0.05). Glomerular filtration rate correlated significantly with free E + NE, free and conjugated dopamine, and inversely with the ratio of conjugated E + NE/ free E + NE in the whole subjects. These findings suggest that raised plasma CA concentration associated with the relative enhancement of extraneuronal inactivations may be relevant to the retarded clearance of circulating CA rather than increased CA release in CRF patients. It is likely that many factors unrelated to sympathetic nerve discharge have a considerable influence on both plasma CA concentration and plasma DBH activity in CRF patients, making them unreliable for studying the role of sympathetic nerve activity in these patients.     

Prevalence and etiology of delayed orthostatic hypotension in adult women

Madhavan G, Goddard AA, McLeod KJ. Prevalence and etiology of delayed orthostatic hypotension in adult women.

Objective

To evaluate the contributing roles of venous status, microvascular filtration, and calf muscle pump activity in the etiology of delayed orthostatic hypotension (OH).

Design

Unblinded within-subjects trial.

Setting

Academic clinical research center.

Participants

Convenience sample of healthy adult women (N=30) with an age range of 30 to 65 years.

Intervention

Plantar micromechanical stimulation applied at a 45-Hz frequency and a 50-μm amplitude for a duration of 30 minutes during upright sitting.

Main Outcome Measure

Diastolic blood pressure (DBP).

Results

White women (mean age, 51.8±1.3y) were recruited and screened for delayed OH. About one quarter (9/33) of the screened subjects showed delayed OH as determined by a significant decrease in blood pressure after at least 15 minutes of quiet sitting. Air plethysmographic assessment provided no evidence of venous insufficiency (venous filling index, >2.5mL/s; venous volume, >80mL) or excessive microvascular filtration in the affected subjects, whereas activation of the calf muscle pump (CMP) through plantar-based micromechanical stimulation consistently resulted in a significant increase in systolic blood pressure (SBP) (ΔSBP=22.8±3.9mmHg, P=.003) and DBP (ΔDBP=20.9±3.3mmHg, P=.002).

Conclusions

About 25% of the adult women studied showed delayed OH during quiet sitting and the proximate cause appears to be neuromuscular in origin, specifically inadequate calf muscle tone, because venous and microvascular filtration status is normative in the delayed OH subpopulation and CMP stimulation reverses the hypotension.