Orthostatic Intolerance Patients Research Articles

Cerebral blood flow and end-tidal CO2 predict lightheadedness during head-up tilt in patients with orthostatic intolerance.

Orthostatic intolerance (OI) is a common problem. Reliable markers of OI are missing, as orthostatic blood pressure and heart rate poorly correlate with orthostatic symptoms. The objective of this study was to assess the relationship between orthostatic lightheadedness and cerebral blood flow. In this retrospective study patients with OI were evaluated at the Autonomic Laboratory of the Department of Neurology, Brigham and Women's Faulkner Hospital, Boston. The 10-minute head-up tilt test was performed as a part of autonomic testing. Orthostatic lightheadedness was evaluated at every minute of the head-up tilt. Heart rate, blood pressure, capnography, and cerebral blood flow velocity (CBFv) in the middle cerebral artery using transcranial Doppler were measured. Repeated-measures design with a linear mixed-effects model was used to evaluate the relationship between orthostatic lightheadedness and hemodynamic variables. Correlation analyses were done by calculating Pearson's coefficient. Twenty-two patients with OI were compared to nineteen controls. Orthostatic CBFv and end-tidal CO2 decreased in OI patients compared to controls (p < 0.001) and predicted orthostatic lightheadedness. Orthostatic heart rate and blood pressure failed to predict orthostatic lightheadedness. The lightheadedness threshold, which marked the onset of lightheadedness, was equal to an average systolic CBFv decrease of 18.92% and end-tidal CO2 of 12.82%. The intensity of lightheadedness was proportional to the CBFv and end-tidal CO2 decline. Orthostatic lightheadedness correlated with systolic CBFv (r=-0.6, p < 0.001) and end-tidal CO2 (r=-0.33, p < 0.001) decline. In conclusion, orthostatic CBFv and end-tidal CO2 changes predict orthostatic lightheadedness and can be used as objective markers of OI.

Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, and feeling faint while maintaining an upright posture. Despite intense investigation, the molecular mechanism of this debilitating condition is still unknown. OI is often manifested by cardiovascular alterations, such as reduced cerebral blood flow, reduced blood pressure, and diminished heart rate. The bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of endothelial nitric oxide synthase (eNOS) enzyme, is tightly coupled with cardiovascular health and circulation. To explore the role of BH4 in ME/CFS, serum samples of CFS patients (n = 32), CFS patients with OI only (n = 10; CFS + OI), and CFS patients with both OI and small fiber polyneuropathy (n = 12; CFS + OI + SFN) were subjected to BH4 ELISA. Interestingly, our results revealed that the BH4 expression is significantly high in CFS, CFS + OI, and CFS + OI + SFN patients compared to age-/gender-matched controls. Finally, a ROS production assay in cultured microglial cells followed by Pearson correlation statistics indicated that the elevated BH4 in serum samples of CFS + OI patients might be associated with the oxidative stress response. These findings suggest that the regulation of BH4 metabolism could be a promising target for understanding the molecular mechanism of CFS and CFS with OI.

Orthostatic intolerance after fast-track knee arthroplasty: Incidence and hemodynamic pathophysiology.

Early postoperative mobilization can be hindered by orthostatic intolerance (OI) due to failed orthostatic cardiovascular regulation. The underlying mechanisms are not fully understood and specific data after total knee arthroplasty (TKA) are lacking. Therefore, we evaluated the incidence of OI and the cardiovascular response to mobilization in fast-track TKA. This prospective observational cohort study included 45 patients scheduled for primary TKA in spinal anesthesia with a multimodal opioid-sparing analgesic regime. OI and the cardiovascular response to sitting and standing were evaluated with a standardized mobilization procedure preoperatively, and at 6 and 24 h postoperatively. Hemodynamic variables were measured non-invasively (LiDCO™ Rapid). Perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, opioid use, and pain during mobilization were recorded. Eighteen (44%) and 8 (22%) patients demonstrated OI at 6 and 24 h after surgery, respectively. Four (10%) and 2 (5%) patients experienced severe OI and terminated the mobilization procedure prematurely. Dizziness was the most common OI symptom during mobilization at 6h. OI was associated with decreased orthostatic responses in systolic, diastolic, mean arterial pressures, and heart rate (all p < .05), while severe OI patients demonstrated impaired diastolic, mean arterial pressures, heart rate, and cardiac output responses (all p < .05). No statistically significant differences in perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, pain, or opioid use were observed between orthostatic tolerant and intolerant patients. Early postoperative OI is common following fast-track TKA. Pathophysiologic mechanisms include impaired orthostatic cardiovascular responses. The progression to severe OI symptoms appears to be primarily due to inadequate heart rate response.

Coefficient of variation of heart rate and blood pressure in rapid identification of children with suspected orthostatic intolerance

Objective: To investigate the clinical value of coefficient of variation of heart rate and blood pressure in rapid identification of children with suspected orthostatic intolerance(OI). Methods: This was a retrospective study. The medical records of 379 children with OI were collected, who were admitted to the Department of Pediatrics of Qilu Hospital of Shandong University from January 2015 to January 2020. Another 20 out-patient children without syncope or syncope aura were selected as control. According to the results of standing test and head-up tilt test (HUTT), all the patients with OI were divided into the following 4 groups: vasovagal syncope (VVS) group, postural tachycardia syndrome (POTS) group, POTS combined with VVS (POTS+VVS) group and HUTT negative group. Then, coefficient of variation of systolic pressure (SBPCV), coefficient of variation of diastolic pressure (DBPCV) and coefficient of variation of heart rate (HRCV) in standing test and HUTT were calculated. Kruskal-Wallis test was used for comparison among the five groups, and Dunnett's T3 method for comparison between two groups. Paired t test was used to compare the coefficient of variation between supine and erect position and tilt position in each group. The predictive values of HRCV,SBPCV and DBPCV for negative HUTT were evaluated by receiver operating characteristic (ROC) curve. Results: Among the 379 children, there were 79 in HUTT negative group, 208 in VVS group, 52 in POTS group, and 40 in POTS+VVS group. The SBPCV of supine-erect position of the control group, HUTT negative group, VVS group, POTS group, POTS+VVS group were (3.8±1.0)%, (5.3±2.2)%, (6.6±3.4)%, (5.9±3.6)%, (6.9±2.8)%, respectively. Similarly, the SBPCV of supine, erect and head-up tilt position were (4.5±0.8)%, (6.0±1.9)%, (7.1±2.6)%, (6.0±2.1)%, (7.3±2.5)%; the DBPCV of supine-erect position were (7.3±1.2)%, (9.1±3.7)%, (9.1±4.9)%, (9.1±4.8)%, (11.6±4.6)%; the DBPCV of supine, erect and tilt position were (7.4±1.1)%, (9.4±2.9)%, (10.1±3.8)%, (9.2±3.3)%, (11.0±4.7)%; the HRCV of supine-erect position were (7.6±2.6)%, (12.9±3.7)%, (16.2±4.3)%, (21.2±5.9)%, (24.9±5.3)%; and the HRCV of supine, erect and tilt position were (8.1±1.6)%, (10.1±2.7)%, (14.1±4.3)%, (15.6±3.7)%, (18.9±4.0)%, respectively. All the indexes showed significant differences among the five groups (χ2=21.91, 25.47, 19.82, 14.65, 104.52, 92.51, all P<0.05). ROC curve analysis showed that when the SBPCV and HRCV of supine-erect position reached 4.4% and 10.5%, the area under the curve of ROC were 0.713 and 0.877, the sensitivity of predicting negative HUTT were 58.2% and 78.5%, and the specificity were 80.0% and 95.0%, respectively. Conclusions: Coefficient of variation of heart rate and blood pressure may serve as potential diagnostic indexes in evaluating autonomic function of OI patients. SBPCV ≥ 4.4% or HRCV ≥ 10.5% of supine-erect position could be an indication of HUTT.

Early Cerebral Hypoperfusion in Patients with Orthostatic Intolerance Without Tachycardia During Head-Up Tilt Test is Independent of Vasovagal Response.

Cerebral hypoperfusion before syncope has been shown in patients with chronic orthostatic intolerance (OI) without tachycardia, but it is unknown if an initial decrease of cerebral blood flow velocity (CBFv) could be related to the vasovagal response (VVR) to head-up tilt test (HUTT). The objective of the study was to compare cardiovascular, cerebrovascular, and autonomic variables during HUTT in OI patients with or without a VVR. We included 74 subjects (58% female, mean age 33 ± 12 years) who underwent a 30-min HUTT and were divided into three groups: OI with VVR positive (VVR+), OI without VVR negative (VVR-), and asymptomatic healthy subjects with negative HUTT (control group). Cardiovascular, cerebrovascular, and autonomic variables were assessed beat-to-beat during HUTT with a Task Force monitor and a trans-cranial Doppler. Mean values were evaluated at baseline and throughout the first 10 min of tilting. Cardiovascular variables were similar in the three groups. Systolic, diastolic, and mean CBFv were similar in VVR+ and VVR-, but both groups had lower CBFv than the control group. Systolic and diastolic CBFv decreased from baseline since min 1 in VVR+ and VVR- and since min 5 in the control group. The mean CBFv had a significant decrease since min 1 compared to baseline in all groups. Spectral indices of heart rate and blood pressure variability showed a similar autonomic response to HUTT in all groups. Patients with chronic OI without tachycardia have early postural cerebral hypoperfusion, regardless of the VVR during HUTT.

Usefulness of Squatting Combined with the Blood Pressure Measurement for Orthostatic Intolerance in Dizziness Clinic

Background Orthostatic intolerance (OI) is a common clinical symptom in dizziness clinic. The head-up tilt table test (HUT) is one of the primary clinical examination for evaluating OI. There is no consensus on the optimum method for diagnosis of orthostatic hypotension (OH). Herein, we performed the additional squat combined with blood pressure (BP) monitoring for OI patients with normal HUT. Methods The study included 32 consecutive patients with orthostatic intolerance for 3 months since April, 2018 (Period I) and 27 patients with orthostatic intolerance for 3 months since April, 2019 (Period II) in dizziness clinic of Chungnam National University Hospital. During Period II, the additional squat combined with BP test was performed for normal HUT results in patients with OI. In squat combined orthostatic BP measurement, the first BP measurement was taken following 3 minutes of rest at the squat position; afterwards the patients were raised upright and the measurement was monitored for 2 minutes, using a continuous beat-to-beat BP monitoring. Results In this study, there was significant difference in OH diagnosis (p<0.001); 40.6% (13/32) by conventional HUT (Period I) vs. 92.5% (25/33) by conventional HUT and additional squat test for normal HUT (Period II). In patients with normal HUT, the positive OH was 86.7% (13/15) by the additional squat combined BP measurement (Period II). Conclusions In addition to HUT, squat test combined with BP measurement might be more informative for understanding and diagnosing the OH, particularly in patients with OI and normal HUT in dizziness clinic. Keywords: Orthostatic intolerance, Tilt table test

Transient Orthostatic Hypertension During Head-Up Tilt Test in Young Adults: A Phenotype of Blood Pressure Variability.

The mechanisms underlying orthostatic hypertension (OHT) remain poorly understood. The authors evaluated the cardiovascular, cerebrovascular dynamics, and autonomic response to head-up tilt test (HUTT) in young adults with symptoms of orthostatic intolerance and transient OHT. Forty-four female subjects were included (34 ± 13 years old) and categorized in three groups after a 30-minute 70° passive HUTT: symptomatic patients with OHT (surge of systolic blood pressure ≥20 mm Hg for at least 5 minutes at any given time during HUTT), orthostatic intolerance (symptomatic patients without orthostatic blood pressure changes), and healthy asymptomatic control subjects. At baseline, OHT patients had lower systolic blood pressure than orthostatic intolerance patients (103 ± 8 vs. 116 ± 10 mm Hg, p < 0.01) and lower baroreflex sensitivity than control subjects (15.8 ± 8.3 vs. 27.1 ± 11.7 ms/mm Hg, p = 0.01). On tilt, cardiac output decreased in OHT patients from 6.1 ± 1.4 L/minute during baseline to 5.2 ± 0.8 L/minute after 10 minutes of HUTT (p = 0.01). In OHT patients at 30 minutes of HUTT, sympathetic efferent heart activity was higher (77.4 ± 14.9 normalized units or nu) than orthostatic intolerant patients (63.5 ± 11.8 nu, p = 0.02) and control subjects (65.8 ± 11.2 nu, p = 0.05). Cerebrovascular resistance in OHT was higher than control subjects after 30 minutes (2.2 ± 0.8 vs. 1.6 ± 0.3 cm/second, respectively, p = 0.02). This study demonstrates that transient OHT can occur at any given time during HUTT. These patients exhibit a decrease in cardiac output and a hyperadrenergic response to tilt.

Clinical Prognostic Factors in Pediatric Patients With Orthostatic Intolerance.

Midodrine is widely used for orthostatic intolerance (OI); however, little is known about the prognostic factors of OI after midodrine treatment. We retrospectively reviewed electronic medical charts to investigate clinical prognostic factors of OI on 159 OI patients aged 7 to 18 years who were treated with midodrine at a children’s hospital. Logistic regression was conducted to clarify predictors for improving symptoms at the first month of the treatment. Patients with orthostatic uncomfortable feeling or fainting were significantly more likely to improve symptoms at the first month of the treatment (odds ratio [OR], 3.48; 95% confidence interval [95%CI], 1.36-8.89), but patients with underweight were significantly less likely to improve symptoms (OR, 0.19; 95%CI, 0.06-0.56). Our results suggest that predictive factors for OI by midodrine treatments are orthostatic symptoms and underweight in pediatric patients. These findings are useful to develop further studies for OI treatments.

The incidence of orthostatic intolerance after bariatric surgery.

SummaryAimsEvery year, over 200 000 individuals undergo bariatric surgery for the treatment of extreme obesity in the United States. Several retrospective studies describe the occurrence of orthostatic intolerance (OI) syndrome after bariatric surgery. However, the incidence of this syndrome remains unknown.Materials and methodsWe used a prospective, de‐identified registry of 4547 patients who have undergone bariatric surgery at Vanderbilt to identify cases of new‐onset OI. Structured chart reviews were conducted for all subjects who reported new‐onset OI post surgery. Cases of OI were confirmed using an operational case definition developed by the Vanderbilt Autonomic Dysfunction Center, and autonomic function tests results were examined for evidence of impaired autonomic function. The cumulative incidence of post‐bariatric surgery OI syndrome was estimated using a life table.ResultsSeven hundred forty‐one of 4547 (16.3%) patients included in our cohort reported new OI symptoms after surgery. After the chart review, we confirmed the presence of post–bariatric surgery OI syndrome in 85 patients, 14 with severe OI requiring pressor agents. At 5 years post surgery, follow‐up is reduced to 15%; the unadjusted 5‐year prevalence of OI was 1.9%. The cumulative incidence of OI syndrome adjusted for loss of follow‐up was 4.2%. Most OI cases developed during weight‐stable months (±5 kg). At the time of identification, 13% of OI cases showed evidence of impaired sympathetic vasoconstrictor activity.ConclusionOI is frequent in the bariatric population, affecting 4.2% of patients within the first 5 years postoperatively. In 13% of post–bariatric surgery OI patients, there was evidence of impaired sympathetic vasoconstriction activity.

Relationship Between the Fecal Microbiota and Depression and Anxiety in Pediatric Patients With Orthostatic Intolerance.

Orthostatic intolerance (OI) is an important health problem for children and adolescents. The onset and exacerbation of OI are strongly affected by psychosocial factors. Intestinal microbial deviations, which are affected by food and lifestyle factors, are an important risk factor for adult psychiatry patients, but their roles in pediatric patients are unclear. The objective of this study was to investigate the intestinal microbiota and its involvement in the mental health of children with OI. Fifty-six fecal samples from pediatric OI patients and 9 samples from healthy children were examined with terminal-restriction fragment length polymorphism analysis from July 2016 to January 2018 at Nihon University Itabashi Hospital, Tokyo, Japan. Bacterial diversity was analyzed using the Shannon-Wiener index and the Simpson index. All OI patients were assessed using 2 different psychological scales: the Children's Depression Inventory and the Children's Manifest Anxiety Scale. The patients were then divided into the following subgroups: depression or nondepression and anxiety or nonanxiety. The mean proportion of Clostridium subcluster XIVa and/or Enterobacteriaceae (operational taxonomic unit [OTU] 940) in the OI patients was significantly higher than that in the healthy controls (P = .02). Among OI patients, Bifidobacterium (OTU 124) was less frequent in the depression group than in the nondepression group. However, depression and anxiety showed no correlation with bacterial diversity. Pediatric OI patients showed deviations in the intestinal bacterial flora. The intestinal flora can serve as a novel therapeutic target for the mental health management of intractable pediatric OI patients.

Cerebral Perfusion Monitoring Using Near-Infrared Spectroscopy During Head-Up Tilt Table Test in Patients With Orthostatic Intolerance.

The head-up tilt table test (HUT) is one of the primary clinical examinations for evaluating orthostatic intolerance (OI). HUT can be divided into three phases: dynamic tilt phase (supine to tilt up), static tilt phase (remain tilted at 70°), and post tilt phase (tilt down back to supine position). Commonly, blood pressure (BP) and heart rate (HR) are monitored to observe for OI symptoms, but are indirect measurements of cerebral perfusion and can lead to inaccurate HUT evaluation. In this study, we implemented a 108-channel near-infrared spectroscopy (NIRS) probe to characterize HUT performance by monitoring cerebral hemodynamic changes for healthy controls (HCs), OI patients with normal HUT results, and OI patients with positive HUT results: vasovagal syncope (VS), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), and orthostatic hypertension (OHT). By the end of the static tilt phase, OI patients typically did not show a complete recovery back to baseline cerebral oxygenation and total blood volume compared to HCs. We characterized the return to cerebral homeostasis by polynomial fitting total blood volume changes and determining the inflection point. The OI patients with normal HUT results, VS, OH, or OHT showed a delay in the return to cerebral homeostasis compared to the HC group during HUT.

Hypocapnic cerebral hypoperfusion: A biomarker of orthostatic intolerance.

The objective of the study was to identify markers of hypocapnic cerebral hypoperfusion (HYCH) in patients with orthostatic intolerance (OI) without tachycardia and without orthostatic hypotension. This single center, retrospective study included OI patients referred for autonomic evaluation with the 10 min tilt test. Heart rate, end-tidal CO2 (ET-CO2), blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery were monitored. HYCH was defined by: (1) Symptoms of OI; (2) Orthostatic hypocapnia (low ET-CO2); (3) Abnormal decline in orthostatic CBFv due to hypocapnia; 4) Absence of tachycardia, orthostatic hypotension, or other causes of low CBFv or hypocapnia. Sixteen subjects met HYCH criteria (15/1 women/men, age 38.5±8.0 years) and were matched by age and gender to postural tachycardia patients (POTS, n = 16) and healthy controls (n = 16). During the tilt, CBFv decreased more in HYCH (-22.4±7.7%, p<0.0001) and POTS (-19.0±10.3%, p<0.0001) compared to controls (-3.0±5.0%). Orthostatic ET-CO2 was lower in HYCH (26.4±4.2 (mmHg), p<0.0001) and POTS (28.6±4.3, p<0.0001) compared to controls (36.9 ± 2.1 mmHg). Orthostatic heart rate was normal in HYCH (89.0±10.9 (BPM), p<0.08) and controls (80.8 ±11.2), but was higher in POTS (123.7±11.2, p<0.0001). Blood pressure was normal and similar in all groups. It is concluded that both HYCH and POTS patients have comparable decrease in CBFv which is due to vasoconstrictive effect of hypocapnia. Blood flow velocity monitoring can provide an objective biomarker for HYCH in OI patients without tachycardia.

Cardiovascular variability in young male and female subjects in health and orthostatic intolerance.

The aim of this study was to investigate the effect of head-up tilt (HUT) test on male and female young patients, diagnosed with orthostatic intolerance (OI), in comparison to male and female healthy subjects. Twenty seven OI patients (21 women, 6 men) and 26 age-matched healthy subjects (13 women, 13 men) were enrolled in a 70° HUT test. In addition to hemodynamic variables, cardiovascular and respiratory parameters were determined using linear and nonlinear methods to analyze heart rate (HRV) and blood pressure variability (BPV). During the complete test, HRV was lower in healthy men than in female controls. Decreased HRV and increased BPV were observed in female patients compared to healthy women. Furthermore, systolic BPV was increased in male and female patients. However, linear (rmssd) and nonlinear (plvar2) parameters indicated that diastolic BPV decreased in male patients during orthostatic phase, but remained unchanged in female patients. Findings indicated gender dependent mechanisms for the regulation of diastolic blood pressure during orthostatic stress in patients.

Investigating the relationship between cardiac interoception and autonomic cardiac control using a predictive coding framework.

Predictive coding models, such as the 'free-energy principle' (FEP), have recently been discussed in relation to how interoceptive (afferent visceral feedback) signals update predictions about the state of the body, thereby driving autonomic mediation of homeostasis. This study appealed to 'interoceptive inference', under the FEP, to seek new insights into autonomic (dys)function and brain-body integration by examining the relationship between cardiac interoception and autonomic cardiac control in healthy controls and patients with forms of orthostatic intolerance (OI); to (i) seek empirical support for interoceptive inference and (ii) delineate if this relationship was sensitive to increased interoceptive prediction error in OI patients during head-up tilt (HUT)/symptom provocation. Measures of interoception and heart rate variability (HRV) were recorded whilst supine and during HUT in healthy controls (N = 20), postural tachycardia syndrome (PoTS, N = 20) and vasovagal syncope (VVS, N = 20) patients. Compared to controls, interoceptive accuracy was reduced in both OI groups. Healthy controls' interoceptive sensibility positively correlated with HRV whilst supine. Conversely, both OI groups' interoceptive awareness negatively correlated with HRV during HUT. Our pilot study offers initial support for interoceptive inference and suggests OI cohorts share a central pathophysiology underlying interoceptive deficits expressed across distinct cardiovascular autonomic pathophysiology. From a predictive coding perspective, OI patients' data indicates a failure to attenuate/modulate ascending interoceptive prediction errors, reinforced by the concomitant failure to engage autonomic reflexes during HUT. Our findings offer a potential framework for conceptualising how the human nervous system maintains homeostasis and how both central and autonomic processes are ultimately implicated in dysautonomia.

Reduced Systolic Volume: Main Pathophysiological Mechanism in Patients with Orthostatic Intolerance?

BackgroundOrthostatic intolerance patients' pathophysiological mechanism is still obscure, contributing to the difficulty in their clinical management.ObjectiveTo investigate hemodynamic changes during tilt test in individuals with orthostatic intolerance symptoms, including syncope or near syncope.MethodsSixty-one patients who underwent tilt test at - 70° in the phase without vasodilators were divided into two groups. For data analysis, only the first 20 minutes of tilting were considered. Group I was made up of 33 patients who had an increase of total peripheral vascular resistance (TPVR) during orthostatic position; and Group II was made up of 28 patients with a decrease in TPVR (characterizing insufficient peripheral vascular resistance). The control group consisted of 24 healthy asymptomatic individuals. Hemodynamic parameters were obtained by a non-invasive hemodynamic monitor in three different moments (supine position, tilt 10' and tilt 20') adjusted for age.ResultsIn the supine position, systolic volume (SV) was significantly reduced in both Group II and I in comparison to the control group, respectively (66.4 ±14.9 ml vs. 81.8±14.8 ml vs. 101.5±24.2 ml; p<0.05). TPVR, however, was higher in Group II in comparison to Group I and controls, respectively (1750.5± 442 dyne.s/cm5 vs.1424±404 dyne.s/cm5 vs. 974.4±230 dyne.s/cm5; p<0.05). In the orthostatic position, at 10', there was repetition of findings, with lower absolute values of SV compared to controls (64.1±14.0 ml vs 65.5±11.3 ml vs 82.8±15.6 ml; p<0.05). TPVR, on the other hand, showed a relative drop in Group II, in comparison to Group I.ConclusionReduced SV was consistently observed in the groups of patients with orthostatic intolerance in comparison to the control group. Two different responses to tilt test were observed: one group with elevated TPVR and another with a relative drop in TPVR, possibly suggesting a more severe failure of compensation mechanisms.

Intravenous Hydration for Management of Medication-Resistant Orthostatic Intolerance in the Adolescent and Young Adult.

Orthostatic intolerance (OI) is common in teenagers (T) and young adults (A). Despite treatment with oral fluids, medication, and exercise, a significant number have symptoms from multiple organ systems and suffer low quality of life (QOL). Previous studies showed that acute intravenous (IV) hydration (IH) could help restore orthostatic tolerance; however, no data are available about the intermediate-term effects of IH. We therefore studied the efficacy of IH to improve QOL and manage medication-refractory OI patients. Our study population consisted of 39 patients (mean age = 16.1 ± 3.3) years; thirty-two were female. Average number of medications failed = 3.1. Average QOL score on self-reported OI questionnaire was 4.2 (normal QOL = 10). IV hydration consisted of normal saline (1-2 l/day, 3-7 days/week). 1) Orthostatic testing revealed Postural Orthostatic Tachycardia (24), Neurally Mediated Hypotension (14) or OI (1). 2) Average orthostatic change in heart rate was 48 ± 18 bpm. 3) IH was performed via intermittent IV access (10), PICC line (22), and Port (7). 4) Duration of IH varied from 1 week to 3.8 years (mean = 29 ± 47 weeks). 5) Overall, 79 % (n = 31) demonstrated clinically improved self-reported QOL. 6) Six patients who discontinued IH requested to restart treatment. (7) Complications consisted of upper extremity deep vein thrombosis (n = 3) and infection (n = 4). IH is an effective therapy to improve QOL in T&A with medication-resistant OI. Most patients continued to report improved QOL once IH was discontinued. IH should be considered a therapeutic option in medication-resistant OI patients with low QOL.

Cerebral hemodynamics in orthostatic intolerance with normal head-up tilt test.

Orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS) are well-known causes of orthostatic intolerance (OI). In addition, there are OI patients who are characterized by the symptoms of OI and lack of abnormal findings in head-up tilt (HUT) test. The aim of this study was to determine the cerebral hemodynamic changes in HUT test of OI patients with normal HUT (OINH). Two hundred and sixty-one OI patients and 50 healthy controls were enrolled in this study. All subjects underwent transcranial Doppler test while performing the HUT test. Forty-five patients had OH, 33 patients had POTS, and 183 patients had OINH. Blood pressures, heart rate, cerebral blood flow velocities (CBFVs), end-tidal carbon dioxide (ET-PCO2 ), cerebral critical closing pressure (CCP), cerebral perfusion pressure (CPP), and cerebral vascular resistance (CVR) were measured during HUT test. We compared the hemodynamic parameters of OINH with those of OH, POTS, and healthy controls. Reduced CBFVs, CPP, and ET-PCO2 and elevated CCP were observed in the HUT test of all four groups. CVR was reduced in three OI patients. The drops in systolic CBFV, CPP, and CVR of OINH patients were greater than those of healthy controls. The changes in parameters in the HUT test of OINH group were not different from those of OH and POTS groups except prominent decrements of CPP and CVR in OH group. Our findings suggest that OINH is true OI sharing the common pathomechanism of OH and POTS.

Does Goal-directed Fluid Therapy Affect Postoperative Orthostatic Intolerance?

Early mobilization is important for postoperative recovery but is limited by orthostatic intolerance (OI) with a prevalence of 50% 6 h after major surgery. The pathophysiology of postoperative OI is assumed to include hypovolemia besides dysregulation of vasomotor tone. Stroke volume-guided fluid therapy, so-called goal-directed therapy (GDT), corrects functional hypovolemia, and the authors hypothesized that GDT reduces the prevalence of OI after major surgery and assessed this in a prospective, double-blinded trial. Forty-two patients scheduled for open radical prostatectomy were randomized into standard fluid therapy (control group) or GDT groups. Both groups received a fixed-volume crystalloid regimen supplemented with 1:1 replacement of blood loss with colloid, and in addition, the GDT group received colloid to obtain a maximal stroke volume (esophageal Doppler). The primary outcome was the prevalence of OI assessed with a standardized mobilization protocol before and 6 h after surgery. Hemodynamic and hormonal orthostatic responses were evaluated. Twelve (57%) versus 15 (71%) patients in the control and GDT groups (P = 0.33), respectively, demonstrated OI after surgery, group difference 14% (CI, -18 to 45%). Patients in the GDT group received more colloid during surgery (1,758 vs. 1,057 ml; P = 0.001) and reached a higher stroke volume (102 vs. 89 ml; P = 0.04). OI patients had an increased length of hospital stay (3 vs. 2 days; P = 0.02) and impaired hemodynamic and norepinephrine responses on mobilization. GDT did not reduce the prevalence of OI, and patients with OI demonstrated impaired cardiovascular and hormonal responses to mobilization.

Benign Paroxysmal Positional Vertigo Is More Commonly Associated with Orthostatic Dizziness than Orthostatic Hypotension

Objectives: Orthostatic dizziness (OD) and positional dizziness (PD) are very common conditions in dizziness clinics, but those two conditions are not clearly separated. We aimed to evaluate the clinical significance of simple OD and OD combined with PD for the diagnosis of benign paroxysmal positional vertigo (BPPV) and orthostatic intolerance (OI). Methods: Patients presenting with OD (n = 102) were divided into two groups according to their symptoms: group PO, presenting with PD as well as OD; group O, presenting with OD. A thorough medical history, physical examination, and vestibular function tests were performed to identify the etiology of the dizziness. Orthostatic vital sign measurement (OVSM) was used to diagnose OI. Results: The majority of patients were in group PO (87.3%). BPPV was the most common cause of OD for all patients (36.3%) and group PO (37.1%), while OI was most common etiology for group O (38.5%). A total of 17 (16.7%) OI patients were identified by OVSM test. Orthostatic hypotension (n = 10) was most frequently found, followed by orthostatic hypertension (n=5), and orthostatic tachycardia (n = 2). Group O showed significantly higher percentage (38.5%) of OI than group PO (13.5%) ( P = 0.039). Conclusions: It is suggested that orthostatic testing such as OVSM or HUTT should be performed as an initial work-up for patients with simple OD. Positional tests for BPPV should be considered as an essential diagnostic test for patients with OD, even though their dizziness is not associated with PD.

Clinical significance of orthostatic dizziness in the diagnosis of benign paroxysmal positional vertigo and orthostatic intolerance

PurposeOrthostatic dizziness (OD) and positional dizziness (PD) are considerably common conditions in dizziness clinic, whereas those two conditions are not clearly separated. We aimed to evaluate the clinical significance of simple OD and OD combined with PD for the diagnosis of benign paroxysmal positional vertigo (BPPV) and orthostatic intolerance (OI). Patients and MethodsPatients presenting with OD (n=102) were divided into two groups according to their symptoms: group PO, presenting with PD as well as OD; group O, presenting with OD. A thorough medical history, physical examination, and vestibular function tests were performed to identify the etiology of the dizziness. Orthostatic vital sign measurement (OVSM) was used to diagnose OI. ResultsThe majority of patients were in group PO (87.3%). BPPV was the most common cause of OD for entire patients (36.3%) and group PO (37.1%), while OI was most common etiology for group O (38.5%). Total of 17 (16.7%) OI patients were identified by OVSM test. Orthostatic hypotension (n=10) was most frequently found, followed by orthostatic hypertension (n=5), and orthostatic tachycardia (n=2). Group O showed significantly higher percentage (38.5%) of OI than group PO (13.5%) (P=0.039). ConclusionIt is suggested that orthostatic testing such as OVSM or head-up tilt table test should be performed as an initial work up for the patients with simple OD. Positional tests for BPPV should be considered as an essential diagnostic test for patients with OD, even though their dizziness is not associated with PD.