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Reducing Orthostatic Intolerance with Oral Rehydration in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

通过口服补液减少肌痛性脑脊髓炎/慢性疲劳综合征患者的体位不耐受

基本信息

批准号：
9207020
负责人：
MARVIN S MEDOW
金额：
$ 20.5万
依托单位：
NEW YORK MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9207020
关键词：
Acute Albumins Blood Blood Pressure Blood Volume Cardiac Output Cerebrovascular Circulation Cholera Chronic Chronic Fatigue Syndrome Cross-Over Studies Data Doppler Ultrasound Effectiveness Electrolytes Etiology Fluid Shifts Gravitation Heart Rate Hematocrit procedure Hour Hydration status Hypotension IV Fluid Infusion procedures Ingestion Intercellular Fluid Intravenous Isotonic Exercise Liquid substance Lower Body Negative Pressure Measurement Measures Mediating Methods Noble Gases Normal saline ORALIT Oral Oscillometry Osmolar Concentration Patient Recruitments Patients Peripheral Peripheral Resistance Physiology Plasma Plethysmography Postural Orthostatic Tachycardia Syndrome Posture Presyncopes Property Randomized Regional Blood Flow Rehydration Solutions Rehydrations Resistance Respiration Rest Route Saline Salts Sodium Sodium Chloride Stress Tests Supination Symptoms Syncope Techniques Testing Tilt-Table Test Time Venous aged electric impedance falls glucose transport healthy volunteer improved intravenous administration neurovascular orthostatic intolerance orthostatic stress pressure programs public health relevance reduce symptoms relating to nervous system response restoration

项目摘要

DESCRIPTION (provided by applicant): We and others have shown that a majority of younger patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have orthostatic intolerance (OI), the inability to tolerate orthostatic stress such as prolonged standing. OI in ME/CFS comprises postural tachycardia syndrome (POTS) in which symptoms occur along with excessive upright heart rate, and neurally mediated hypotension (NMH) in which symptoms occur along with an upright fall in blood pressure. The causes of OI are diverse but are clearly initiated by postural contraction of central blood volume (BV) by gravitational translocation of 500-800 mL of blood from the upper to the lower body. Intravenous central BV expansion with isotonic saline is commonly and effectively used to reduce OI regardless of etiology, but has complications if used long term. Usual forms of oral hydration fail to provide similar benefit. Interestingly, a specific isotonic oral rehydration solution (ORS W.H.O. formula), making use of co-transport of glucose and sodium, has been shown to efficiently rehydrate cholera patients suggesting an ability to increase central BV rivaling intravenous fluids. Since the circulatory effects of saline or ORS BV expansion are incompletely understood, we propose to study the neurovascular physiology of fluid loading during orthostatic stress in ME/CFS patients with POTS or NMH, comparing results with healthy control subjects. We hypothesize that equal volumes of ORS is not inferior and may be superior to intravenous saline infusion in increasing intravascular and interstitial fluid volume and improving orthostatic tolerance. Using noninvasive measurements of heart rate and blood pressure by Finapres and oscillometry, cardiac output and peripheral arterial resistance by inert gas rebreathing, cerebral blood flow velocity by transcranial Doppler ultrasound, and regional fluid shifts by impedance and venous occlusion plethysmography, we have acquired preliminary data in ME/CFS patients with OI demonstrating superior restoration of orthostatic tolerance with ORS. We will recruit patients aged 15-29 years who have confirmed ME/CFS with OI, including 15 with NMH and 15 with POTS, and compare them to 15 healthy volunteer subjects. In Specific Aim 1 we will measure BV by Daxor iodinated albumin technique before orthostatic stress imposed by step-wise lower body negative pressure (LBNP) to measure the threshold for OI. Relative changes in BV using serial hematocrits in OI patients will be compared to data from control subjects similarly tested. In Specific Aim 2, all subjects will be randomized to receive saline or ORS in a cross over study. On one day, total BV and neurovascular properties will be measured in patients and control subjects before and 1 hour after completing one liter administration of intravenous normal saline infusion or ORS. On another day (separated by 1 week), we will repeat measurements using the other hydration route. We will perform LBNP on each day following saline or ORS to determine whether orthostatic intolerance and circulatory physiology are improved similarly with equivolumic IV saline or ORS hydration.

描述(由申请人提供)：我们和其他人已经证明，大多数患有肌肉痛脑脊髓炎/慢性疲劳综合征(ME/CFS)的年轻患者患有立位不耐受(OI)，即无法耐受立位压力，如长时间站立。ME/CFS中的OI包括体位性心动过速综合征(POTS)和神经介导性低血压(NMH)，POTS的症状伴随着心率过快而出现，NMH的症状伴随着血压的垂直下降而出现。OI的原因是多方面的，但显然是由500-800毫升血液从上半身向下半身的重力输送引起的体位中央血容量(BV)收缩。静脉中心静脉扩张加等渗盐水是一种常用且有效的减少OI的方法，但长期使用会出现并发症。通常形式的口服补水不能提供类似的益处。有趣的是，一种特殊的等渗口服补液液(ORS W.H.O.公式)，利用葡萄糖和钠的共同转运，已被证明能够有效地重新水化霍乱患者，这表明有能力增加中枢BV与静脉输液相媲美。由于生理盐水或ORS BV扩张对循环的影响还不完全清楚，我们建议研究患有POTS或NMH的ME/CFS患者在立位应激期间液体负荷的神经血管生理学，并与健康对照组的结果进行比较。我们假设等容量的ORS在增加血管内和间质液体容量和改善立位耐力方面并不比静脉注射生理盐水更好。使用Finapres和ORS无创测量心率和血压，惰性气体再呼吸法测量心输出量和外周动脉阻力，经颅多普勒超声测量脑血流速度，阻抗和静脉阻塞体积图测量局部液体移位，我们获得了ORS治疗OI的ME/CFS患者的初步数据，表明ORS具有良好的立位耐力恢复。我们将招募15-29岁确诊为ME/CFS合并OI的患者，包括15名NMH患者和15名POTS患者，并将他们与15名健康志愿者进行比较。具体目的1采用Daxor碘化白蛋白技术测定立位应激前下体负压(LBNP)时的BV，测定OI阈值。OI患者使用系列血细胞的BV的相对变化将与类似测试的对照受试者的数据进行比较。在具体目标2中，在交叉研究中，所有受试者将被随机接受生理盐水或口服补液。在第一天，患者和对照组将在完成一升静脉生理盐水输注或ORS前和一小时后测量总BV和神经血管特性。在另一天(间隔一周)，我们将使用另一种水化途径重复测量。我们将在生理盐水或ORS后的每一天进行下体负压试验，以确定立位耐力和循环生理是否与等容静脉盐水或ORS水化相似。