Salt supplementation in the management of orthostatic intolerance: Vasovagal syncope and postural orthostatic tachycardia syndrome.

Salt supplementation is a common non-pharmacological approach to the management of recurrent orthostatic syncope or presyncope, particularly for patients with vasovagal syncope (VVS) or postural orthostatic tachycardia syndrome (POTS), although there is limited consensus on the optimal dosage, formulation and duration of treatment. Accordingly, we reviewed the evidence for the use of salt supplementation to reduce susceptibility to syncope or presyncope in patients with VVS and POTS. We found that short-term (~3 months) salt supplementation improves susceptibility to VVS and associated symptoms, with little effect on supine blood pressure. In patients with VVS, salt supplementation is associated with increases in plasma volume, and an increase in the time taken to provoke a syncopal event during orthostatic tolerance testing, with smaller orthostatic heart rate increases, enhanced peripheral vascular responses to orthostatic stress, and improved cerebral autoregulation. Responses were most pronounced in those with a baseline sodium excretion <170 mmol/day. Salt supplementation also improved symptoms, plasma volume, and orthostatic responses in patients with POTS. Salt supplementation should be considered for individuals with recurrent and troublesome episodes of VVS or POTS without cardiovascular comorbidities, particularly if their typical urinary sodium excretion is low, and their supine blood pressure is not elevated. The efficacy of the response, in terms of the improvement in subjective and objective markers of orthostatic intolerance, and any potential deleterious effect on supine blood pressure, should be routinely monitored in individuals on high salt regimes.

Dynamic cerebral autoregulation is preserved in neurally mediated syncope.

To test whether cerebral autoregulation is impaired in patients with neurally mediated syncope (NMS), we evaluated 15 normal subjects and 37 patients with recurrent NMS. Blood pressure (BP), heart rate, and cerebral blood velocity (CBV) (transcranial Doppler) were recorded at rest and during 80 degrees head-up tilt (HUT). Static cerebral autoregulation as assessed from the change in cerebrovascular resistance during HUT was the same in NMS and controls. Properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between BP and CBV estimated from filtered data segments (0.02-0.8 Hz). During the 3 min preceding syncope, dynamic cerebral autoregulation of subjects with NMS did not differ from that of controls nor did it change over the course of HUT in patients with NMS or in control subjects. Dynamic cerebral autoregulation was also unaffected by the degree of orthostatic intolerance as inferred from latency to onset of syncope. We conclude that cerebral autoregulation in patients with recurrent syncope does not differ from that of normal control subjects.

Cerebral autoregulation in orthostatic intolerance.

Many of the primary symptoms of orthostatic intolerance (fatigue, diminished concentration) as well as some of the premonitory symptoms of neurally mediated syncope (NMS) are thought to be due to cerebral hypoperfusion. Transcranial Doppler measurements of middle cerebral artery blood velocity (CBV) is at present the only technique for assessing rapid changes in cerebral blood flow, and hence for evaluating dynamic cerebral autoregulation. However, controversies exist regarding data interpretation. At syncope, during the collapse of blood pressure (BP), diastolic CBV diminishes, whereas systolic CBV is maintained. Some consider this increase in CBV pulsatility to be indicative of a paradoxical increase in cerebrovascular resistance (CVR) prior to syncope. Others note that mean CBV decreases much less than does mean BP, implying that cerebral autoregulatory mechanisms are intact and functioning at syncope. Similarly, there is no evidence of impaired dynamic cerebral autoregulation, as measured by standard linear transfer-function analysis, in patients with NMS. Some patients with exaggerated postural tachycardia (POTS) have been found to have an excessive decrease in CBV during head-up tilt. Controversy exists as to whether this decrease results from an excessive sympathetic outflow to the cerebral vasculature or from hyperventilation. However, many other equally symptomatic patients with a similar hemodynamic profile of exaggerated tachycardia during head-up tilt have normal CBV changes during this maneuver and have normal dynamic cerebral autoregulation as determined by transfer-function analysis. Whether these discrepancies reflect different pathologies in patients with POTS is currently unknown.

Motor conduction alterations in patients with lumbar spinal stenosis following the onset of neurogenic claudication.

The pathogenesis of neurogenic claudication is thought to lie in relative ischemia of cauda equina roots during exercise. In this study we will evaluate the effect of the transient ischemia brought on by exercise on motor conduction in patients suffering from lumbar spinal stenosis (LSS). We will also evaluate the sensitivity of motor evoked potentials (MEPs) in detecting motor conduction abnormalities before and after the onset of neurogenic claudication. Thirty patients with LSS and 19 healthy volunteers were enrolled in the study. All LSS patients had a history of neurogenic claudication and the diagnosis was confirmed with a CT myelogram. Both groups underwent a complete electrophysiological evaluation of the lower extremities. The motor evoked potential latency time (MEPLT) and the peripheral motor conduction time (PMCT) were measured. The subjects were asked to walk on a flat surface until their symptoms were reproduced. A new set of electrophysiological tests was then performed. Exercise did not produce claudication in any of the control group subjects. Twenty-seven patients did have claudication. The pre-exercise MEPLT and nerve conduction studies in the control group fell within the normal range. In the patient group, 19 patients had increased baseline values for MEPLT to at least one muscle. There was a significant difference between the MEPLT and the PMCT values measured before and after exercise in the patients with signs of neurological deficit. This difference was not found to be significant in patients without neurological deficits (t-test P < 0. 05). It may be concluded that exercise increases the sensitivity of MEPs in detecting the roots under functional compression in LSS.

Orthostatic intolerance in the chronic fatigue syndrome.

This study aims to investigate the prevalence and pathophysiology of orthostatic intolerance (OI) and its potential contribution to symptoms of a group of unselected patients with chronic fatigue syndrome (CFS). Seventy five patients (65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical suspicion as to the likelihood of observing laboratory evidence of OI was assigned. Laboratory investigation consisted of beat-to-beat recordings of heart rate, blood pressure (Finapres), and stroke volume (impedance cardiograph) while supine and during 80 degrees head-up tilt (HUT), during rhythmic deep breathing (6 breaths/min) and during the Valsalva maneuver. The responses of 48 age-matched healthy controls who had no history of OI were used to define the range of normal responses to these three maneuvers. Forty percent of patients with CFS had OI during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven tachycardia (> 35 bpm averaged over the whole of the head-up tilt) and six a mixture of tachycardia and syncope. Eight of 48 controls exhibited neurally-mediated syncope. The responses to the Valsalva maneuver and to deep breathing were similar in controls and patients. On average, the duration of disease and patient age were significantly less and the onset of symptoms was more often subacute in patients with OI than in those without OI. We conclude that there exists a clinically identifiable subgroup of patients with CFS and OI that differs from control subjects and from those with CFS without OI for whom treatment specifically aimed at improving orthostatic tolerance may be indicated.

The importance of orthostatic intolerance in the chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis is a clinically defined syndrome characterized by persistent or relapsing debilitating fatigue for longer than 6 months in the absence of any definable medical diagnosis. The cause of this syndrome is unknown. Symptoms of orthostatic intolerance, such as disabling fatigue, dizziness, diminished concentration, tremulousness, and nausea, are often found in patients with CFS. In this review, we critically evaluate the relationship between orthostatic intolerance and CFS. Particular emphasis is placed on clinical diagnosis, laboratory testing, pathophysiology, and therapeutic management. It is hoped that this review will provide a stimulus for further study of this complex and disabling condition.

Cerebrovascular and cardiovascular measurements during neurally mediated syncope induced by head-up tilt.

BACKGROUND AND PURPOSE: This study examines changes in systemic hemodynamics and in cerebral blood velocity that occur during neurally mediated syncope (NMS) to determine whether cerebral autoregulation is intact or impaired in patients with recurrent NMS. METHODS: Beat-to-beat recordings of heart rate, blood pressure (volume clamp photoplethysmography), stroke volume (impedance cardiography), and right middle cerebral artery blood velocity (transcranial Doppler sonography) were performed at rest and during 80 degrees head-up tilt. Twelve patients with NMS and 10 healthy control subjects were studied. RESULTS: Baseline values and the initial response to head-up tilt of control subjects and patients with NMS were similar. The mean latency to onset of syncope was 11.8 +/- 11.1 minutes. At syncope, heart rate, systolic and diastolic blood pressure, and diastolic cerebral blood velocity decreased significantly, whereas systolic cerebral blood velocity did not change. Calculated cerebrovascular resistance was significantly reduced from 1.85 +/- 0.60 to 1.32 +/- 0.27 mm Hg/cm per second, whereas the pulsatility index increased from 0.92 +/- 0.16 to 1.52 +/- 0.21. We never observed a change in cerebral blood velocity before the rapid decline in blood pressure, nor did we observe any significant change in respiratory pattern. CONCLUSIONS: The decrease in cerebrovascular resistance during NMS indicates that the integrity of cerebrovascular autoregulation is maintained even when syncope is imminent. The selective loss of diastolic flow during syncope and the increase in pulsatility index are likely caused by collapse of downstream vessels as diastolic blood pressure decreases below the critical closing pressure of cerebral vessels.

Is the heart "empty' at syncope?

Neurally-mediated syncope (NMS) is thought to be reflexly triggered by vagal cardiac ventricular afferents that are activated by impaired cardiac filling. If this hypothesis is true then maneuvers that increase venous pooling should progressively diminish cardiac volume triggering syncope once a threshold decrease in cardiac filling is reached. Beat-to-beat recordings of heart rate, blood pressure (Finapres) and stroke volume (impedance cardiograph) were made at rest and during head-up tilt (80 degrees) in twenty controls and in fourteen patients with recurrent NMS (group 1). Hemodynamic profiles of controls and group 1 were compared. In eleven additional patients with NMS (group 2) we measured cardiac chamber volume from apical two or four-chamber views or stroke volume from Doppler measurements of the left ventricular outflow tract at rest and during tilt. Baseline values and initial response to head-up tilt of controls and group 1 patients were similar. A small negative trend in blood pressure and total peripheral resistance was present for at least 250 s before the onset of syncope. Stroke volume remained stable during this presyncopal period and increased at syncope. The profile of stroke volume changes using impedance cardiography mirrored those obtained using Doppler (5 subjects). Reliable echocardiographic measurements of cardiac chamber size were obtained in five subjects and did not change during tilt, presyncope or syncope. These data show that there is no significant decrease in cardiac volume before syncope that could serve as a trigger of syncope.

Postural tachycardia syndrome (POTS).

In orthostatic intolerance, the patient develops symptoms while standing that are relieved when the patient assumes a supine position. Different degrees of orthostatic intolerance exist, but not a system of grading severity. We have developed a system that grades the severity of orthostatic intolerance by the three-pronged criteria of the rapidity of development and the severity of orthostatic symptoms, the ability of the subject to withstand orthostatic stresses, and the degree of interference with daily living. In this article, this system is presented, and one disorder, postural tachycardia syndrome (POTS), is examined in some detail.

The effect of severe brainstem injury on heart rate and blood pressure oscillations.

To determine whether an intact brainstem is essential for the generation of neurogenically mediated fluctuations of R-R intervals and blood pressure, three patients with cerebellar lesions causing severe brainstem compression or death, one patient with a large pontine infarct and one patient with a pontine haemorrhage, were studied. Time-frequency maps (based on a modified Wigner distribution) were constructed from blood pressure and R-R interval signals in these patients with brainstem injury and were compared with maps of normal control subjects. Low frequency sympathetically mediated rhythms (0.01-0.12 Hz) in systolic and diastolic pressure remained detectable but attenuated in patients with brainstem injury whereas there was an almost complete loss of normal R-R intervals rhythmicity over 0.01 to 0.5 Hz range. These data suggest that fluctuations in R-R intervals require an intact brainstem, whereas low frequency approximately 0.06 +/- 0.02 Hz blood pressure rhythms may be preserved by spinal sympathetic circuitry.

Comparison of the postural tachycardia syndrome (POTS) with orthostatic hypotension due to autonomic failure.

Postural tachycardia syndrome (POTS) is characterized by orthostatic dizziness, tremulousness, tachycardia and variable blood pressure changes. Since some POTS patients have a marked reduction in pulse pressure on standing, a major mechanism of their symptoms might be venous pooling. We therefore studied the cardiovascular response to head-up tilt, Valsalva maneuver and deep breathing in: control subjects (n = 11; F = 8; M = 3; 39.2 +/- 14.4 years); patients with orthostatic hypotension secondary to autonomic failure (n = 11; F = 9; M = 2; 61.7 +/- 13.0 years), and patients with POTS (n = 15); F = 13; M = 2; 32.3 +/- 10.6 years). Blood pressure was measured with a Finapres, and cardiac output, stroke volume, end-diastolic volume and thoracic impedance (TFI) were measured by thoracic electrical bioimpedance. During tilt (in contrast to patients with orthostatic hypotensiom), patients with POTS had excessive tachycardia (P < 0.001), a normal to excessive total peripheral resistance increase, and an exaggerated decrease in stroke volume (P < 0.001) and end-diastolic volume (P < 0.001). These findings suggest that sympathetic arteriolar function remains relatively intact but that sympathetic venomotor function is selectively impaired. These findings may have significant implications for the treatment of patients with POTS.

Accuracy of beat-to-beat noninvasive measurement of finger arterial pressure using the Finapres: a spectral analysis approach.

OBJECTIVE: Our objective was to test the accuracy of noninvasive recordings of finger arterial pressure (FAP) using the Ohmeda Finapres (Ohmeda Monitoring Systems, Englewood, CO). METHODS: Twenty patients, aged 20 to 78 years, requiring admission to the intensive care unit and placement of intraarterial catheters participated in the study. Systolic and diastolic pressures were derived from 1-hr recordings of beat-to-beat FAP and from ipsilaterally recorded intraarterial pressure (IAP) signals. In all 20 cases, we analyzed beat-to-beat discrepancies between the actual magnitude of FAP and IAP, as well as the distribution of the consecutive differences within each of the two signals. In 10 cases, spectral analysis of the frequency content of both signals was performed. RESULTS: The average systolic FAP (128.1 +/- 22.4 mm Hg) did not differ from IAP (127.1 +/- 19.7 mm Hg), whereas diastolic FAP (78.1 +/- 11.9 mm Hg) was greater (71.5 +/- 10.3 mm Hg) (p < 0.001). No differences in the linear trends of FAP and IAP were observed. Overall, systolic FAP and IAP were discrepant by 0.84 +/- 13.3 mm Hg (-21.82 to 25.8 mm Hg); diastolic FAP and IAP were discrepant by 6.67 +/- 5.23 mm Hg (2.68 to 13.05 mm Hg). Despite discrepancies in the magnitude of the two signals, the contour of IAP approximated that of FAP. Spectral analysis demonstrated good reproducibility and coherence between diastolic IAP and FAP fluctuations in both low-frequency (0.01 to 0.15 Hz) and high-frequency (0.15 to 0.33 Hz) bands. The low-frequency fluctuations in FAP systolic pressure were significantly amplified (p < 0.001) (gain 1.75), whereas the high-frequency fluctuations were not. CONCLUSIONS: Over the course of 1 hr, FAP followed the contour and frequency content of IAP.

New investigations of autonomic nervous system function.

Sensitive noninvasive techniques are available for beat-to-beat measurement of heart rate, blood pressure, and stroke volume. These allow for the assessment of the dynamic response capacity of the autonomic nervous system to stimuli that perturb baseline activity. In this review, the accuracy of volume clamp photoplethysmography for the measurement of finger arterial pressure and impedance cardiography for the measurement of cardiac output is critically evaluated. The utility of spectral analysis of blood pressure and heart rate for the routine assessment of autonomic function is discussed. It is suggested that these techniques will afford valuable information concerning central autonomic regulatory mechanisms and their dysfunction.

Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?

To characterize the idiopathic postural orthostatic tachycardia syndrome (POTS), we reviewed the records of all patients aged 20 to 51 who presented to the Mayo Autonomic Reflex Laboratory and who exhibited tachycardia at rest or during head-up tilt. These patients were usually women who experienced an acute onset of persistent lightheadedness and fatigue or gastrointestinal dysmotility. In seven patients, a viral illness may have preceded the onset of symptoms. In two instances, signs and symptoms of a small-fiber sensory neuropathy were present. Laboratory evaluation of autonomic function revealed increased diastolic blood pressure to tilt (5/16), increased Valsalva ratio, marked decrease in phase II of the Valsalva maneuver with normal phase IV overshoot, and normal forced respiratory sinus arrhythmia. Abnormal quantitative sudomotor axon reflex test and thermoregulatory sweat test and an excessive orthostatic increase of catecholamines were found in some patients. We conclude that in many instances POTS may be a manifestation of a mild form of acute autonomic neuropathy.

Gender related differences in the cardiovascular responses to upright tilt in normal subjects.

The heart rate and blood pressure responses to head-up tilt of 80 degrees was studied in 20 normal men and 21 normal women aged 20-50 years (mean age 31.1 +/- 7.1 years). The heart rate increase in females during tilt was 73% that of males, whereas the increase in diastolic pressure during tilt was 29% of males. Expressed in relation to values obtained supine, heart rate increases on average 30.3% in men as compared to 21.5% in women whereas diastolic pressure increases by 15.2% in men as compared to an increase of only 4.3% in women. The data indicates that the cardiovascular response of normal females to upright tilt differs significantly from that of normal males. This attenuated responsiveness to orthostasis in women relative to men may predispose women to postural insufficiency and may account for the predominance of symptomatic women with clinically mild dysautonomia.