Orthostatic Intolerance In Patients Research Articles

Associations of Orthostatic Hypotension and Orthostatic Intolerance with Domain-Specific Cognitive Decline in Patients with Early Parkinson Disease: An 8-Year Follow-up

ObjectiveAlthough orthostatic hypotension (OH) and orthostatic intolerance (OI) are prevalent in patients with Parkinson disease (PD), it remains unclear how these conditions primarily affect the trajectory of decline in specific cognitive domains. This study aimed to explore the effects of OH and OI on longitudinal domain-specific cognitive changes in patients with PD. DesignAn 8-year follow-up of the Parkinson Progression Markers Initiative cohort study. Setting and ParticipantsA total of 403 patients with early, untreated PD and 195 matched healthy controls were included. They were classified into OH, OI, and normal groups. OH was defined according to the international consensus, and OI was defined as the presence of orthostatic symptoms without meeting the criteria for OH. MethodsThe patients underwent detailed neuropsychological testing annually for up to 8 years of follow-up. Linear mixed effects models were used to investigate the associations between OH, OI, and longitudinal cognitive changes. ResultsThe prevalence of both OH and OI in patients with PD was significantly higher than that in controls (13.4% vs 7.2%, P = .002, for OH, and 29.3% vs 14.4%, P < .001, for OI). The OH group in patients with PD showed a faster decline in Letter-Number Sequencing (LNS) (β = −0.11, 95% CI −0.20 to −0.02, t = −2.44, P = .015) and Semantic Fluency Test (SFT) (β = −0.44, 95% CI –0.81 to −0.08, t = −2.42, P = .016) scores than the normal group. Similarly, the OI group showed a steeper decline in LNS (β = −0.08, 95% CI –0.14 to −0.01, t = −2.20, P = .028) and SFT (β = −0.36, 95% CI –0.63 to −0.08, t = −2.55, P = .011) scores compared to the normal group. There were no significant longitudinal changes in the other neuropsychological test scores between the groups. Conclusions and ImplicationsBoth OH and OI may be associated with a faster decline in executive function among cognitive domains of patients with PD. These findings may highlight the potential importance of orthostatic blood pressure control in PD patients with OH and even those with orthostatic symptoms without OH.

Orthostatic Intolerance and Chiari I Malformation

Individuals with Chiari malformation can present with symptoms of fatigue, lightheadedness, and syncope-the cardinal features of orthostatic intolerance. Similar orthostatic symptoms can complicate the clinical course following Chiari decompression. The presence of orthostatic intolerance in patients with Chiari malformation is not surprising given the location of the major circulatory control centers and their pathways in the brainstem. This article reviews the normal physiologic response to upright posture and the common forms of orthostatic intolerance encountered in clinical practice. The authors describe the relationship between orthostatic intolerance and Chiari malformation and provide suggestions regarding the evaluation and management of these disorders.

Frequency of hemodynamic response to orthostatic stress in heart failure with reduced ejection fraction, associations with clinical blood pressure

Aim. To assess hemodynamic response to active standing test (AST) with beat-to-beat blood pressure (BP) monitoring, their association with office BP and symptoms of orthostatic intolerance in patients with heart failure (HF).Material and methods. Outpatient HF patients with documented left ventricular ejection fraction &lt;40%, followed up in a HF center and receiving optimal medical therapy, underwent AST with beat-to-beat non-invasive BP monitoring.Hemodynamic response was assessed according to the European Federation of Autonomic Societies criteria.Results. The study included 87 patients (mean age, 57±10 years; men, 76%). Normal hemodynamic response to orthostatic stress was observed in 36 (41,4%) patients. Pathological response prevailed during the first minute of orthostatic stress — initial orthostatic hypotension (OH) (n=29, 33,3%) and delayed BP recovery (n=18, 20,7%). Classical OH was detected in 4 (4,6%) patients. There was no orthostatic hypertension, defined as an increase in systolic BP (SBP) ≥20 mm Hg. According to office BP, hypotension was observed in 19 (21,8%) patients (SBP &lt;90 mm Hg in 4 patients and 90-100 mm Hg in 15), hypertension (SBP &gt;140 mm Hg) in 11 (12,6%) patients. Pathological response to orthostatic stress were more often observed in office SBP &gt;140 mm Hg compared to SBP ≤140 mmHg (90,9% and 53,9%, p=0,020).Orthostatic intolerance was noted in 43 (49,4%) patients and were not associated with the level of office SBP (p=0,398) or pathological responses to orthostatic stress (p=0,758 for initial OH and p=0,248 for delayed BP recovery).Conclusion. The pathological hemodynamic response in AST with beat-to-beat BP monitoring in ambulatory patients with HF is most often represented by initial OH and delayed BP recovery associated with office SBP &gt;140 mmHg. The frequency of symptoms of orthostatic intolerance did not differ between groups depending on the presence of an inadequate response to orthostatic stress.

Dynamic cerebral autoregulation during early orthostatic exercise in patients with severe traumatic brain injury: Further exploratory analyses from a randomized clinical feasibility trial

In patients with severe traumatic brain injury, there is limited evidence of the clinical effect of early orthostatic exercise, although such exercise may strengthen systemic or cerebral hemodynamic responses to head-up tilt, thereby minimizing orthostatic intolerance. We measured dynamic cerebral autoregulation (dCA) and the occurrence of orthostatic intolerance after four weeks of regular orthostatic exercise by head-up tilt using a tilt table with integrated stepping using the ERIGO® tilt-table and comparing it to standard care. Thirty-four patients with severe traumatic brain injury admitted to a neurocritical care unit were included in this randomized clinical trial. Middle cerebral artery blood flow velocity (MCAv), non-invasive mean arterial pressure, heart rate and PaCO2 were recorded; dCA was measured by the non-invasive mean flow index (nMxa). Transition from the supine position to head-up tilt triggered a 10–16% decrease in MCAv and increased nMxa in both groups at all time points (P < 0.05), with no differences between groups. There was no difference in the number of episodes with orthostatic intolerance (5 vs 3; 1 vs 2; 1 vs 0) at baseline, two weeks and four weeks, respectively, and no association between changes in PaCO2-adjusted nMxa and the occurrence of orthostatic reactions (P = 0.35). Early orthostatic exercise does not affect dynamic cerebral autoregulation and does not protect against orthostatic intolerance in patients with severe traumatic brain injury. Trial registration: ClinicalTrials.gov identifier: NCT02924649. Registered on 3rd October 2016.

Paradigm shift to disequilibrium in the genesis of orthostatic intolerance in patients with myalgic encephalomyelitis and chronic fatigue syndrome

BackgroundOrthostatic intolerance (OI) markedly impairs activities of daily living in patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome. OI is surmised to be a cardiovascular symptom correlated with cerebral hypo-perfusion and exaggerated sympathetic activation. Postural instability or disequilibrium may be part of the etiology of OI. MethodsThe study comprised 72 patients with ME (18 men, 54 women; mean age, 37 ± 10 years) who underwent neurological examinations and the 10 min standing test. We quantified disequilibrium (instability upon standing with feet together and eyes shut), ability to complete the 10 min standing test, and postural orthostatic tachycardia (POT) during the test. ResultsDisequilibrium was detected in 23/72 (32%) patients and POT in 16 (22%). Nineteen (26%) patients failed to complete the 10 min standing test; disequilibrium was significantly more common in the 19- patient subgroup than in the 53-patient test-completing subgroup (89% vs. 11%, p < 0.01). However, the rate of POT was not different between the groups (21% vs. 23%, p = 1.00). Compared with the 49 (68%) patients without disequilibrium, the 23 (32%) patients with disequilibrium were significantly more likely to have failed to complete the test (74% vs. 4%, p < 0.01). The rate of POT was comparable between the groups (23% vs. 22%, p = 1.00). Among patients with disequilibrium who failed to complete the 10 min standing test and had a previous record, 6/8 had completed the test 6–24 months earlier when all six had reported no disequilibrium. ConclusionDisequilibrium should be recognized as an important cause of OI in patients with ME.

Impact of Patisiran, an RNAi Therapeutic, on Orthostatic Intolerance in Patients with Hereditary Transthyretin-Mediated Amyloidosis (766)

Impact of Patisiran, an RNAi Therapeutic, on Orthostatic Intolerance in Patients with Hereditary Transthyretin-Mediated Amyloidosis (766)

P5344Paradigme shift to disequilibrium in the genesis of orthostatic intolerance in patients with chronic fatigue syndrome

Abstract Background Chronic fatigue syndrome (CFS) characterized by severe disabling fatigue and prolonging post-exertional malaise. The dysfunction of the central nervous system associated with myalgic encephalomyelitis (ME) has been postulated as the main cause of CFS. Orthostatic intolerance (OI) causes a marked reduction in the activities of daily living and impairs the quality of life in patients with ME/CFS. OI has been surmised to be a cardiovascular symptom with cerebral hypo-perfusion and exaggerated sympathetic nervous activation. Purpose Postural instability or disequilibrium may be involved in the etiology of OI because postural stability is an essential element for static balance. Methods The study comprised 72 patients with ME/CFS (18 men and 54 women; mean age, 37±10 years), who underwent neurological examinations and the active 10-min standing test. Results Disequilibrium defined as instability on standing with their feet together and eyes shut, was detected in 23 (32%) patients while postural orthostatic tachycardia in 16 (22%). Compared with 49 patients without disequilibrium, patients with disequilibrium more prevalently failed to complete the 10-min standing test (74% vs. 4%, p&lt;0.01) and body sway was significantly more prevalently observed during the test (100% vs. 12%, p&lt;0.01). The performance status score was significantly higher in patients with disequilibrium than those without it (median: 7 vs. 5, p&lt;0.01), suggesting more severely restricted activity of daily living in the former. The prevalence of postural orthostatic tachycardia during the standing test was comparable between the patients with disequilibrium (23%) and those without it (22%, p=1.00). The 19 (26%) patients who failed to complete the 10-min standing test had disequilibrium more prevalently than those who completed it (89% vs. 11%, p&lt;0.01). Performance status score was significantly higher in patients who failed to complete it than those who completed it (median: 6 vs. 5, p&lt;0.01), suggesting more severe restriction of activity of daily living in the former. Significantly higher rates of disequilibrium (89% vs. 11%, p&lt;0.01), unstable standing on one leg (84% vs. 17%, p&lt;0.01) as well as abnormal tandem gait (79% vs. 11%, p&lt;0.01) were noted in patients who failed to complete it than those who completed it. Body sway during the standing test was significantly more prevalently observed in the patients who failed to complete it than those who completed it (89% vs. 23%, p&lt;0.01). The prevalence of postural orthostatic tachycardia during the standing test was comparable between the patients who failed to complete it and those who completed it (21% vs. 23%, p=1.00). Among the patients who failed to complete it 8 had the previous study records which revealed that 6 of them had completed it 6–24 months before when all the 6 patients had had no disequilibrium. Conclusion Disequilibrium should be recognized as an important cause of OI in patients with ME/CFS.

Impact of Patisiran, an RNAi Therapeutic, on Orthostatic Intolerance in Patients with Hereditary Transthyretin-Mediated Amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease which can impact numerous organs, including peripheral and autonomic nerves and heart. Orthostatic intolerance (OI), caused by amyloid deposition in the autonomic nervous system, is commonly reported in patients with hATTR amyloidosis. OI increases the risk that patients will experience clinically significant events, such as presyncope, syncope, and falls. In the Phase 3 APOLLO study, patisiran demonstrated improvement in OI. This analysis further describes the impact of patisiran on OI symptomatology. APOLLO was an international, randomized (2:1), double-blinded, placebo-controlled study of patisiran 0.3mg/kg or placebo IV q3W in patients with hATTR amyloidosis with polyneuropathy (NCT01960348). COMPASS-31 is a patient-reported autonomic symptoms questionnaire containing 31-items evaluating 6 autonomic domains. In the OI domain, patients were asked, “In the past year, have you ever felt faint, dizzy, ‘goofy’, or had difficulty thinking soon after standing up from a sitting or lying position.” Change in presence and severity of these OI symptoms collected from the OI domain of COMPASS-31 were evaluated descriptively. APOLLO enrolled 225 patients: median age 62 years, 74% male, 43% V30M, FAP Stage 1 (46%) and 2 (53%), 56% in the pre-defined cardiac subpopulation. At baseline, about two-thirds of patients reported mild to severe symptoms of OI in the past year. After 18 months, patisiran-treated patients were 3-fold more likely to report improvement in OI symptoms compared to placebo (30% vs 10%, respectively). Patisiran-treated patients were also less likely to worsen on these symptoms compared to placebo-treated patients after 18 months (14% vs 23%, respectively). Following 18 months of treatment, patients treated with patisiran were three times more likely to improve in their OI symptoms versus their own baseline compared to placebo. These data reinforce the clinical benefit of patisiran in addressing the debilitating autonomic symptoms of hATTR amyloidosis.

The etiologic relation between disequilibrium and orthostatic intolerance in patients with myalgic encephalomyelitis (chronic fatigue syndrome)

BackgroundOrthostatic intolerance (OI) causes a marked reduction in the activities of daily living in patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome. Most symptoms of OI are thought to be related to cerebral hypo-perfusion and sympathetic activation. Because postural stability is an essential element of orthostatic tolerance, disequilibrium may be involved in the etiology of OI. Methods and resultsThe study comprised 44 patients with ME (men, 11 and women, 33; mean age, 37±9 years), who underwent neurological examinations and 10-min standing and sitting tests. Symptoms of OI were detected in 40 (91%) patients and those of sitting intolerance were detected in 30 (68%). Among the 40 patients with OI, disequilibrium with instability on standing with their feet together and eyes shut, was detected in 13 (32.5%) patients and hemodynamic dysfunction during the standing test was detected in 19 (47.5%); both of these were detected in 7 (17.5%) patients. Compared with 31 patients without disequilibrium, 13 (30%) patients with disequilibrium more prevalently reported symptoms during both standing (100% vs. 87%, p=0.43) and sitting (92% vs. 58%, p=0.06) tests. Several (46% vs. 3%, p<0.01) patients failed to complete the 10-min standing test, and some (15% vs. 0%, p=0.15) failed to complete the 10-min sitting test. Among the seven patients with both hemodynamic dysfunction during the standing test and disequilibrium, three (43%) failed to complete the standing test. Among the 6 patients with disequilibrium only, 3 (50%) failed while among the 12 patients with hemodynamic dysfunction only, including 8 patients with postural orthostatic tachycardia, none (0%, p=0.02) failed. ConclusionsPatients with ME and disequilibrium reported not only OI but also sitting intolerance. Disequilibrium should be recognized as an important cause of OI and appears to be a more influential cause for OI than postural orthostatic tachycardia in patients with ME.

Cardiovascular characteristics of chronic fatigue syndrome.

Patients with chronic fatigue syndrome (CFS) commonly exhibit orthostatic intolerance. Abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli was previously described in numerous studies. The aim of the current study was to describe cardiological and clinical characteristics of Italian patients with CFS. All of the patients were of Caucasian ethnicity and had been referred to our center, the Cardiology Department of the University Hospital of Pavia (Pavia, Italy) with suspected CFS. A total of 44 patients with suspected CFS were included in the present study and the diagnosis was confirmed in 19 patients according to recent clinical guidelines. The characteristics at baseline of the population confirm findings from various previous reports regarding the prevalence in females with a female to male ratio of 4:1, the age of onset of the pathology and the presence of previous infection by the Epstein-Barr virus, cytomegalovirus and other human herpesviruses. Despite the current data indicating that the majority of the cardiological parameters investigated are not significantly different in patients with and without CFS, a significant association between the disease and low levels of blood pressure was identified. Other pilot studies revealed a higher prevalence of hypotension and orthostatic intolerance in patients with CFS. Furthermore, many of the CFS symptoms, including fatigue, vertigo, decreased concentration, tremors and nausea, may be explained by hypotension.

Orthostatic Intolerance in Older Persons: Etiology and Countermeasures.

Orthostatic challenge produced by upright posture may lead to syncope if the cardiovascular system is unable to maintain adequate brain perfusion. This review outlines orthostatic intolerance related to the aging process, long-term bedrest confinement, drugs, and disease. Aging-associated illness or injury due to falls often leads to hospitalization. Older patients spend up to 83% of hospital admission lying in bed and thus the consequences of bedrest confinement such as physiological deconditioning, functional decline, and orthostatic intolerance represent a central challenge in the care of the vulnerable older population. This review examines current scientific knowledge regarding orthostatic intolerance and how it comes about and provides a framework for understanding of (patho-) physiological concepts of cardiovascular (in-) stability in ambulatory and bedrest confined senior citizens as well as in individuals with disease conditions [e.g., orthostatic intolerance in patients with diabetes mellitus, multiple sclerosis, Parkinson's, spinal cord injury (SCI)] or those on multiple medications (polypharmacy). Understanding these aspects, along with cardio-postural interactions, is particularly important as blood pressure destabilization leading to orthostatic intolerance affects 3–4% of the general population, and in 4 out of 10 cases the exact cause remains elusive. Reviewed also are countermeasures to orthostatic intolerance such as exercise, water drinking, mental arithmetic, cognitive training, and respiration training in SCI patients. We speculate that optimally applied countermeasures such as mental challenge maintain sympathetic activity, and improve venous return, stroke volume, and consequently, blood pressure during upright standing. Finally, this paper emphasizes the importance of an active life style in old age and why early re-mobilization following bedrest confinement or bedrest is crucial in preventing orthostatic intolerance, falls and falls-related injuries in older persons.

A Shape Memory Alloy-Based Compression Therapy Prototype Tested With Individuals in Seated Position

Orthostatic intolerance in patients can occur secondary to concomitant venous pooling and enhanced capillary filtration when standing upright, and is one of the principle causes of syncope or fainting. Compression therapy is commonly recommended for the management of syncope based on the assumption that it increases venous return. Technologies currently used include compression stockings, whose efficacy has, however, been challenged, and intermittent pneumatic pressure devices, which highly restrict the patients' mobility. This paper therefore investigates a novel active compression brace (ACB), which could potentially provide intermittent pressure while not restricting movements. The ACB, actuated by shape memory alloy (SMA) wires, in this work was tested with twelve healthy individuals in a seated position. The experimental observation showed that the ACB can apply a constant initial pressure to the leg similar to commercial compression stockings and also produce intermittent pressure exceeding 30 mmHg. A comparison between analytical and experimental results showed a maximum of 2.08 mmHg absolute averaged difference among all the participants. A correlation analysis showed that the normalized root-mean-square deviation (NRMSD) between the experimental and analytical results had a significant negative correlation with the estimated total calf circumference minus the calf fat cross-sectional area (CSA). A calibration formula, accounting for fat and circumference of the leg, was introduced to account for these two parameters. The comfort of the ACB was also compared to two other available compression devices using questionnaires. No participants reported discomfort in terms of pressure, skin irritation, or heat generated by the ACB.

Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a constellation of signs and symptoms that occur when a patient is upright and relieved by recumbence. Currently, no drugs are labeled for the treatment for POTS. Droxidopa is an orally administered amino acid that is converted to norepinephrine and thought to improve both blood pressure and symptoms in patients with orthostatic intolerance. To appraise the effect of Droxidopa in a clinical setting in patients with POTS refractory to other forms of treatment. A retrospective study of patients with POTS at our Syncope and Autonomic Disorders Center. Three hundred fifty-two patients were screened, 54 of them were prescribed Droxidopa and found to be eligible to include in our study. Symptoms of orthostatic intolerance, side effects of therapy and response to treatment. Statistical analyses were done using SPSS software. Thirty-seven patients were included in data analysis. Patients who failed to follow up, didn't obtain Droxidopa due to insurance and cost concerns, had hypertensive response to therapy or had allergic reaction were excluded from data analysis. The most frequently reported symptom was dizziness in 91.9% of patients, followed by syncope and fatigue in 70.3% and 67.6% of patients, respectively. Symptoms of dizziness, syncope and fatigue were reported less after treatment; 75.7%, 51.4% and 40.5%, respectively. There was no statistically significant difference in standing or sitting blood pressure before and after treatment. Despite the improvement in some symptoms. Only 27% of patients reported improved quality of life after treatment. Of total, 40.5% of patients stopped the treatment either due to side effects or ineffectiveness. Droxidopa appears to improve some symptoms of orthostatic intolerance in patients with POTS but has diminutive impact on quality of life and blood pressure. Further assessment in large clinical trials is needed to evaluate its efficacy.

Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle.

The etiology of chronic fatigue syndrome (CFS) is unknown. Myalgic encephalomyelitis (ME) has been recently postulated to be the cause of CFS. Orthostatic intolerance (OI) has been known as an important symptom in predicting quality of life in CFS patients. Cardiac function may be impaired in patients with ME. The presence or absence of OI was determined both symptomatically and by using a 10-min stand-up test in 40 ME patients. Left ventricular (LV) dimensions and function were determined echocardiographically in the ME patients compared to 40 control subjects. OI was noted in 35 (97%) of the 36 ME patients who could stand up quickly. The mean values for the cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic diameter (EDD), LV end-systolic diameter, stroke volume index, cardiac index and LV mass index were all significantly smaller in the ME group than in the controls. Both a small LVEDD (<40 mm, 45 vs. 3%) and a low cardiac index (<2 l/ min/mm2, 53 vs. 8%) were significantly more common in the ME group than in the controls. Both heart rate and LV ejection fraction were similar between the groups. In conclusion, a small LV size with a low cardiac output was common in ME patients, in whom OI was extremely common. Cardiac dysfunction with a small heart appears to be related to the symptoms of ME.

Impaired cardiac function due to small heart and orthostatic intolerance in patients with myalgic encephalomyelitis

Purpose: The etiology of chronic fatigue syndrome (CFS) remains unclarified. Recently, dysfunction of central nervous system by myalgic encephalomyelitis (ME) has been postulated as the cause of CFS. International Consensus Criteria identify patients with ME who are more physically debilitated and have greater physical and cognitive impairments. Orthostatic intolerance (OI) with symptoms of disabling fatigue, dizziness, diminished concentration, tremulousness and nausea while standing, appears to be a core symptom of ME, impairing the most basic activities of daily living. Cardiovascular dysfunction in association with a small heart or a small left ventricle (LV) and low cardiac output may be related to the pathophysiology of ME. Methods: Consecutive 40 patients who fullfilled the International Consensus Criteria for ME (14 males and 26 females, 31±10 years of age) and 40 age- and sex- matched sedentary control subjects (Controls) were studied. OI was determined either by subjective symptoms or by 10-min standing test. LV dimensions and function were determined echocardiographically. Results: OI was prevalent (95%) in ME. The mean heart rate was not significantly different between ME and Controls (68±11 vs. 70±11 beats/min, NS). The mean values of cardiothoracic ratio (39±5 vs. 43±4%, p<0.01), systolic (109±9 vs. 120±10 mmHg, p<0.05) and diastolic pressures (68±9 vs. 78±8 mmHg, p<0.05), LV end-diastolic (41±6 vs. 44±3 mm, p<0.01) and end-systolic (25±5 vs. 27±3 mm, p<0.05) dimensions, stroke volume index (32±8 vs. 38±6 ml/m2, p<0.01), cardiac index (2.1±0.4 vs. 2.7±0.5 ml/min/m2, p<0.01) and LV mass index (57±16 vs. 70±17 g/m2, p<0.01) were all significantly smaller in ME than in Controls. A smaller LV end-diastolic dimension (<40 mm) was significantly more prevalently noted in ME than in Controls (45% vs. 3%, p<0.01). A lower cardiac index (< 2 l/min/m2) was more prevalent in ME than in Controls (53% vs. 8%, p<0.01). The mean values of both LV fractional shortening (39±6 vs. 39±4%, NS) and LV ejection fraction (69±7 vs. 69±4%, NS) were quite comparable between the groups. Conclusions: OI was prevalent in ME. Both systolic and diastolic blood pressures were low in ME. A small size of LV associated with low cardiac output due to diminished stroke volume was frequently observed in ME. A small heart appears to be related to the genesis of ME via both cerebral and systemic hypoperfusion, which could make it difficult for patients to meet the demands of everyday activity. A small heart with impaired cardiac performance due to decreased preload appears to be an important target for the treatment of ME.

Orthostatic Intolerance Ambulation in Patients Using Patient Controlled Analgesia

BackgroundOpioid analgesics are widely used to reduce postoperative pain and to enhance post-operative recovery. However, orthostatic intolerance (OI) induced by opioid containing intravenous patient controlled analgesia (IPCA) may hinder postoperative recovery. This study investigated factors that affect OI in patients receiving IPCA for postoperative pain control.MethodsOI was instantly evaluated at the time of first ambulation in 175 patients taking opioid containing IPCA after open and laparoscopic subtotal gastrectomies. Patients were classified as having OI if they experienced dizziness, nausea/vomiting, blurred vision, headache, somnolence and syncope. Factors contributing to OI were assessed with logistic regression analysis.ResultsOut of 175 patients, 61 (52.6%) male and 44 (74.6%) female patients experienced OI at the time of first ambulation. The frequency of OI related symptoms were dizziness (97, 55.4%), nausea (46, 26.3%), headache (9, 5.1%), blurred vision (3, 1.7%) and vomiting (2, 1.1%). Significant risk factors for OI were gender (P=0.002) and total amount of opioids administered (P=0.033).ConclusionsThe incidence of OI is significantly higher in male than in female patients and is influenced by the opioid dose.

Orthostatic intolerance during early mobilization following video-assisted thoracic surgery

Early postoperative mobilization is crucial for early ambulation to reduce postoperative pulmonary complications after lung resection. However, orthostatic intolerance (OI) may delay patient recovery, leading to complications. It is therefore important to understand the prevalence of and predisposing factors for OI following video-assisted thoracic surgery (VATS), which have not been established. This study evaluated the incidence of OI, impact of OI on delayed ambulation, and predisposing factors associated with OI in patients after VATS. This retrospective cohort study consecutively analyzed data from 236 patients who underwent VATS. The primary outcome was defined as OI with symptoms associated with ambulatory challenge on postoperative day 1 (POD1), including dizziness, nausea and vomiting, feeling hot, blurred vision, or transient syncope. Multivariate logistic regression was performed to identify independent factors associated with OI. Of the 236 patients, 35.2 % (83) experienced OI; 45.8 % of these could not ambulate at POD1, compared with 15.7 % of patients without OI (P < 0.001). Factors independently associated with OI included advanced age [odds ratio 2.83 (1.46-5.58); P = 0.002], female gender [odds ratio 2.40 (1.31-4.46); P = 0.004], and postoperative opioid use [odds ratio 2.61 (1.23-5.77); P = 0.012]. Use of thoracic epidural anesthesia was not independently associated with OI [odds ratio 0.72 (0.38-1.37); P = 0.318]. Postoperative OI was common in patients after VATS and significantly associated with delayed ambulation. Advanced age, female gender, and postoperative opioid use were identified as independent predisposing factors for OI.

Erythropoietin in the Treatment of Postural Orthostatic Tachycardia Syndrome

Erythropoietin has been reported to improve symptoms of orthostatic intolerance in patients suffering from orthostatic hypotension. Previous reports on the use of erythropoietin in patients with postural orthostatic tachycardia (POTS) have included only a very small number of patients. In the current study, we report on the use of erythropoietin in patients with refractory POTS. The study was approved by the institutional review board. A retrospective nonrandomized analysis was performed on 39 patients evaluated at our autonomic center for POTS from 2003 to 2010. The diagnosis of POTS was based on patient history, physical examination, and response to head-up tilt-table testing. The mean follow-up period was 6 months. The patients were included in the current study if they had a diagnosis of POTS with severe symptoms of orthostatic intolerance and were refractory to the commonly used medications. All these patients were started on erythropoietin, and the response to therapy was considered successful if it provided symptomatic relief. We screened 200 patients with POTS and found 39 patients (age 33 ± 12, 37 females) to be eligible for inclusion in the current study. The response to the treatment was assessed subjectively in each patient and was obtained in a retrospective fashion from patient charts and physician communications. Eight (21%) patients demonstrated no improvement in symptoms after administration of erythropoietin. Three (8%) patients showed an improvement in symptoms of orthostatic intolerance of <3 months. Twenty-seven (71%) patients demonstrated sustained improvement in their symptoms of orthostatic intolerance at the mean follow-up of 6 months. Erythropoietin significantly improved sitting diastolic blood pressure but had no effect on other hemodynamic parameters. In a select group of POTS patients who are refractory to commonly used medications, erythropoietin may help improve symptoms of orthostatic intolerance.

Small Heart With Low Cardiac Output for Orthostatic Intolerance in Patients With Chronic Fatigue Syndrome

The etiology of chronic fatigue syndrome (CFS) is unknown. Orthostatic intolerance (OI) is common in CFS patients. Recently, small heart with low cardiac output has been postulated to be related to the genesis of both CFS and OI. Small heart is associated with OI in patients with CFS. Study CFS patients were divided into groups of 26 (57%) CFSOI(+) and 20 (43%) CFSOI(-) according to the presence or absence of OI. In addition, 11 OI patients and 27 age- and sex-matched control subjects were studied. Left ventricular (LV) dimensions and function were determined echocardiographically. The mean values of cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic dimension, LV end-systolic dimension, stroke volume index, cardiac index, and LV mass index were all significantly smaller in CFSOI(+) patients than in CFSOI(-) patients and healthy controls, and also in OI patients than in controls. A smaller LV end-diastolic dimension (<40 mm) was significantly (P<0.05) more prevalently noted in CFSOI(+) (54%) and OI (45%) than in CFSOI(-) (5%) and controls (4%). A lower cardiac index (<2 L/min/mm(2)) was more prevalent in CFSOI(+) (65%) than in CFSOI(-) (5%, P<0.01), OI (27%), and controls (11%, P<0.01). A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well-defined and predominant subgroup of CFS.

Autonomic Dysfunction Presenting as Orthostatic Intolerance in Patients Suffering From Mitochondrial Cytopathy

Disturbances in autonomic nervous system function have been reported to occur in patients suffering from mitochondrial cytopathies. However, there is paucity of literature on the occurrence of orthostatic intolerance (OI) in these patients. We report on a series of patients diagnosed with mitochondrial cytopathy who developed features of autonomic dysfunction in the form of OI. This was a single-center report on a series of 6 patients who were followed in our clinic for orthostatic intolerance. All of these patients had a diagnosis of mitochondrial cytopathy on the basis of muscle biopsy and were being followed at a center specializing in the treatment of mitochondrial disorders. This study was approved by our local institutional review board. Each of the patients had suffered from symptoms of fatigue, palpitations, near syncope, and syncope. The diagnosis of OI was confirmed by head-up tilt test. Collected data included demographic information, presenting symptoms, laboratory data, tilt-table response, and treatment outcomes. Six patients (3 females) were identified for inclusion in this report. The mean age of the group was 48 ± 8 years (range, 40-60 years). All of these patients underwent head-up tilt table testing and all had a positive response that reproduced their clinical symptoms. Among those having an abnormal tilt-table pattern, 1 had a neurocardiogenic response, 1 had a dysautonomic response, and 4 had a postural orthostatic tachycardia response. All but 1 patient reported marked symptom relief with pharmacotherapy. The patient who failed pharmacotherapy received a dual-chamber closed-loop pacemaker and subsequently reported marked improvement in her symptoms with elimination of her syncope. Orthostatic intolerance might be a significant feature of autonomic nervous system dysfunction in patients suffering from mitochondrial cytopathy.