Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV.NEW & NOTEWORTHY We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.

Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

Study protocol for the Heads-Up trial: a phase II randomized controlled trial investigating head-up tilt sleeping to alleviate orthostatic intolerance in Parkinson's Disease and parkinsonism.

BACKGROUND: In persons with Parkinson's Disease (PD) or certain forms of atypical parkinsonism, orthostatic hypotension is common and disabling, yet often underrecognized and undertreated. About half of affected individuals also exhibit supine hypertension. This common co-occurrence of both orthostatic hypotension and supine hypertension complicates pharmacological treatments as the treatment of the one can aggravate the other. Whole-body head-up tilt sleeping (HUTS) is the only known intervention that may improve both. Evidence on its effectiveness and tolerability is, however, lacking, and little is known about the implementability. METHODS: In this double-blind multicenter randomized controlled trial (phase II) we will test the efficacy and tolerability of HUTS at different angles in 50 people with PD or parkinsonism who have both symptomatic orthostatic hypotension and supine hypertension. All participants start with one week of horizontal sleeping and subsequently sleep at three different angles, each maintained for two weeks. The exact intervention will vary between the randomly allocated groups. Specifically, the intervention group will consecutively sleep at 6°, 12° and 18°, while the delayed treatment group starts with a placebo angle (1°), followed by 6° and 12°. We will evaluate tolerability using questionnaires and compliance to the study protocol. The primary endpoint is the change in average overnight blood pressure measured by a 24-hour ambulatory blood pressure recording. Secondary outcomes include orthostatic blood pressure, orthostatic tolerance, supine blood pressure, nocturia and various other motor and non-motor tests and questionnaires. DISCUSSION: We hypothesize that HUTS can simultaneously alleviate orthostatic hypotension and supine hypertension, and that higher angles of HUTS are more effective but less tolerable. The Heads-Up trial will help to clarify the effectiveness, tolerability, and feasibility of this intervention at home and can guide at-home implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551377; Date of registration: September 22, 2022.

Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Differences in Heart Rate Variability in the Frequency Domain between Different Groups of Patients.

Background and Objectives: Heart rate variability (HRV) is defined as a physiological variation in duration between sinus beats. The aim of this study was to research and analyze the HRV between various groups of patients. Materials and Methods: A retrospective study was conducted in an outpatient setting. Patients who had undergone a tilt-table test were selected for this study and were divided into three groups based on their self-reported health anamnesis: group 1 (n = 84, mean age 45.8 ± 17.8) consisted of patients with no known orthostatic intolerance or neurodegenerative disease, group 2 consisted of patients with a known or suspected orthostatic intolerance (n = 50, mean age 46.5 ± 18.6), and group 3 consisted of patients with a known or suspected neurodegenerative disorder (n = 29, mean age 55.6 ± 20.4). During the tilt-table test, HRV frequency-domain parameters-normalized low frequency (LFnu) and high frequency (HFnu), absolute powers-absolute low frequency (LF-RRI), absolute high frequency (HF-RRI), and LF/HF ratio-were recorded during 5 min rest in the supine position. Results: Group 1 had a reduced LFnu at 52.93% (SD: 18.00) compared to group 2 at 58.57% (18.06) and group 3 at 61.80% (SD: 17.74), and group 1 had increased HFnu: group 1-47.08% (SD: 17.97), group 2-41.41% (SD: 18.03), and group 3-38.16% (SD: 14.7). LFnu and HFnu differences were statistically significant (p < 0.05). LF-RRI was reported as follows: group 1-531.32 ms2 (SD: 578.57), group 2-346.2 ms2 (SD: 447.96), and group 3-143.21 ms2 (SD: 166.96). HF-RRI was reported as follows: group 1-835.87 ms2 (SD: 1625.42), group 2-297.46 ms2 (SD: 507.15), and group 3-70.83 ms2 (SD: 75.67). LF-RRI and HF-RRI comparisons between groups were statistically significant (p < 0.001). LF/HF ratios were reported as follows: group 1-1.91 (SD: 2.29), group 2-2.43 (SD: 2.33), and group 3-2.54 (SD: 2.17). LF/HF ratio comparisons between groups were statistically significant at p < 0.05. Conclusions: This study shows that patients with known or suspected orthostatic intolerance and neurodegenerative disorders have reduced HRV, possibly caused by reduced parasympathetic modulation. HRV in patients with known or suspected neurodegenerative disorders is reduced more severely than in patients with orthostatic disorders. Other studies in HRV have indicated a possible increase of risk in cardiovascular disorders in patients with reduced HRV, and therefore, HRV analysis could be a potential clinical diagnostic tool. However, the lack of universally agreed upon methodology, reference values, and possible external and internal factor influence hinders the introduction of HRV examinations into wider clinical practice.

Analysis of orthostatic intolerance symptoms in patients with premature ejaculation.

OBJECTIVE: The autonomic nervous system (ANS) plays an important role in maintaining physiological regulation. It regulates the body's response to many variable situations. Orthostatic intolerance (OI) is one of the most important signs of autonomic dysfunction. Autonomic dysfunction is known to cause premature ejaculation (PE) by disturbing the balance in erection and ejaculation cycles. Considering that OI may develop due to autonomic dysfunction in patients with PE, we hypothesized that OI symptoms would increase in these patients. The aim of our study was to investigate the relationship between orthostatic intolerance and PE. PATIENTS AND METHODS: This case-control study included a total of 39 patients with PE and 47 volunteers without PE. All subjects were assessed using the self-reported Orthostatic Grading Scale (OGS). In addition, the validated five-item Turkish version of the Premature Ejaculation Diagnostic Tool (PEDT) was used to evaluate PE. The PE group included patients with a PEDT score ≥ 11. RESULTS: The mean ages of the PE and control groups were 38.2 ± 7.8 and 40.5 ± 9.1 years, respectively (p = 0.137). The mean PEDT scores of the PE and control groups were 13.9 ± 3.6 and 6.6 ± 2.9, respectively (p < 0.0001), and their mean OGS scores were 5.6 ± 2.4 and 1.6 ± 1.3, respectively (p < 0.0001). A statistically significant correlation was found between the PEDT and OGS scores (r: 0.686, p < 0.0001). CONCLUSIONS: The orthostatic intolerance symptoms of patients with PE were higher than those of the control group. There was a correlation between the severity of PE and the severity of orthostatic intolerance. This is the first study in the literature to reveal a relationship between orthostatic intolerance and PE.

Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.

Postoperative orthostatic intolerance following fast-track unicompartmental knee arthroplasty: incidence and hemodynamics-a prospective observational cohort study.

BACKGROUND: Early postoperative mobilization is essential for early functional recovery but can be inhibited by postoperative orthostatic intolerance (OI). Postoperative OI is common after major surgery, such as total knee arthroplasty (TKA). However, limited data are available after less extensive surgery, such as unicompartmental knee arthroplasty (UKA). We, therefore, investigated the incidence of OI as well as cardiovascular and tissue oxygenation responses during early mobilization after UKA. METHODS: This prospective single-centre observational study included 32 patients undergoing primary UKA. Incidence of OI and cardiovascular and tissue oxygenation responses during mobilization were evaluated preoperatively, at 6 and 24 h after surgery. Perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain during mobilization and opioid usage were recorded. RESULTS: During mobilization at 6 h after surgery, 4 (14%, 95%CI 4-33%) patients experienced OI; however, no patients terminated the mobilization procedure prematurely. Dizziness and feeling of heat were the most common symptoms. OI was associated with attenuated systolic and mean arterial blood pressure responses in the sitting position (all p < 0.05). At 24 h after surgery, 24 (75%) patients had already been discharged, including three of the four patients with early OI. Only five patients were available for measurements, two of whom experienced OI; one terminated the mobilization procedure due to intolerable symptoms. We observed no statistically significant differences in perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain, or opioid usage between orthostatic intolerant and tolerant patients. CONCLUSIONS: The incidence of orthostatic intolerance after fast-track unicompartmental knee arthroplasty is low (~ 15%) and is associated with decreased orthostatic pressure responses. Compared to the previously described orthostatic intolerance incidence of ~ 40% following total knee arthroplasty, early orthostatic intolerance is uncommon after unicompartmental knee arthroplasty, suggesting a procedure-specific component. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov; registration number: NCT04195360, registration date: 13.12.2019.

Impact of COVID-19 infection on baseline autonomic symptoms in patients with preexisting postural tachycardia syndrome and orthostatic intolerance: A retrospective study.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) and dysautonomia following a SARS-CoV-2 infection have been recently reported. The underlying mechanism of dysautonomia is not well understood. The impact of this viral illness on the underlying autonomic symptoms has not been studied in patients with a pre-existing POTS diagnosis. Our study aims to report the impact of a COVID-19 infection on patients with preexisting POTS, both during the acute phase of the disease and post-recovery. METHODS: Institutional Review Board (IRB) approval was obtained to access charts of the study subjects. All patients with known POTS disease who acquired COVID-19 infection between April 2020 and May 2021 were included. The end point of the study was worsening POTS related symptoms including orthostatic dizziness, palpitation, fatigue and syncope/ presyncope post COVID-19 infection that required escalation of therapy. Basic demographics, details of POTS diagnosis, medications, Additional information regarding COVID 19 infection, duration of illness, need for hospitalization, worsening of POTS symptoms, need for ED visits, the type of persisting symptoms and vaccination status were obtained from the retrospective chart review. RESULTS: A total of 41 patients were studied. The alpha-variant was the most common causing SARS-CoV-2 infection. 27% (11 patients) of them had tested positive for COVID- 19 infection more than once. About 38 (92.7%) of them reported having worsening of their baseline POTS symptoms during the active infection phase. About 28 patients (68%) experienced worsening of their dysautonomia symptoms for at least 1-6 months post infection. Nearly 30 patients (73.2%) required additional therapy for their symptom control and improvement. CONCLUSIONS: Patients with pre-existing POTS, most experienced a worsening of their baseline autonomic symptoms after suffering the COVID-19 infection which required additional pharmacotherapy for their symptom improvement.

Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study.

PURPOSE: To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state. METHODS: A cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests. RESULTS: In CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process. CONCLUSION: Our data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.

Plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.

BACKGROUND: Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine. METHODS: Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis. RESULTS: A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05). CONCLUSIONS: The levels of choline-related metabolites and glutamate-related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.

Cardiovascular adaptations in microgravity conditions.

Gravity has had a significant impact on the evolution of life on Earth with organisms developing necessary biological adaptations over billions of years to counter this ever-existing force. There has been an exponential increase in experiments using real and simulated gravity environments in the recent years. Although an understanding followed by discovery of counter measures to negate diminished gravity in space had been the driving force of research initially, there has since been a phenomenal leap wherein a force unearthly as microgravity is beginning to show promising potential. The current review summarizes pathophysiological changes that occur in multiple aspects of the cardiovascular system when exposed to an altered gravity environment leading to cardiovascular deconditioning and orthostatic intolerance. Gravity influences not just the complex multicellular systems but even the survival of organisms at the molecular level by intervening fundamental cellular processes, directly affecting those linked to actin and microtubule organization via mechano-transduction pathways. The reach of gravity ranges from cytoskeletal rearrangement that regulates cell adhesion and migration to intracellular dynamics that dictate cell fate commitment and differentiation. An understanding that microgravity itself is not present on Earth propels the scope of simulated gravity conditions to be a unique and useful environment that could be explored for enhancing the potential of stem cells for a wide range of applications as has been highlighted here.

Clinical and endocrine features of orthostatic intolerance detected in patients with long COVID.

Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.

Impact of vertical positioning on lung aeration among mechanically ventilated intensive care unit patients: a randomized crossover clinical trial.

OBJECTIVE: To assess the impact of different vertical positions on lung aeration in patients receiving invasive mechanical ventilation. METHODS: An open-label randomized crossover clinical trial was conducted between January and July 2020. Adults receiving invasive mechanical ventilation for > 24 hours and < 7 days with hemodynamic, respiratory and neurological stability were randomly assigned at a 1:1 ratio to the sitting position followed by passive orthostasis condition or the passive orthostasis followed by the sitting position condition. The primary outcome was lung aeration assessed using the lung ultrasound score (score ranges from 0 [better] to 36 [worse]). RESULTS: A total of 186 subjects were screened; of these subjects, 19 were enrolled (57.8% male; mean age, 73.2 years). All participants were assigned to receive at least one verticalization protocol. Passive orthostasis resulted in mean lung ultrasound scores that did not differ significantly from the sitting position (11.0 versus 13.7; mean difference, -2.7; [95%CI -6.1 to 0.71; p = 0.11). Adverse events occurred in three subjects in the passive orthostasis group and in one in the sitting position group (p = 0.99). CONCLUSION: This analysis did not find significant differences in lung aeration between the sitting and passive orthostasis groups. A randomized crossover clinical trial assessing the impact of vertical positioning on lung aeration in patients receiving invasive mechanical ventilation is feasible. Unfortunately, the study was interrupted due to the need to treat COVID-19 patients.ClinicalTrials.gov registry: NCT04176445.

Acrocianosis como primera manifestación de síndrome de taquicardia postural ortostática en dos adolescentes / Acrocyanosis as the first manifestation of orthostatic postural tachycardia syndrome in two adolescents

La acrocianosis desencadenada por la bipedestación como signo principal de la taquicardia postural ortostática (POTS, por su sigla en inglés) es poco conocida, aunque bien descrita en la bibliografía especializada. Se describen dos casos clínicos de adolescentes que consultaron en el Servicio de Urgencias por acrocianosis e intolerancia al ortostatismo. El primer paciente, de 13 años, presentó un aumento de la frecuencia cardíaca de 40 latidos por minuto (lpm) al pasar del decúbito a la bipedestación. El segundo, de 14 años, presentó un aumento de la frecuencia cardíaca hasta 125 lpm al incorporarse. En ambos, la tensión arterial y los estudios complementarios fueron normales. El POTS se define en la edad pediátrica como una intolerancia al ortostatismo que se acompaña de aumento de la frecuencia cardíaca excesiva sin hipotensión arterial. Conocer la acrocianosis como primer signo de presentación es de utilidad para el diagnóstico de esta enfermedad y para evitar estudios complementarios innecesarios.

Acrocyanosis triggered by standing position as the main sign of postural orthostatic tachycardia (POTS) is little known but well described in scientific literature. In pediatric age, POTS is defined as orthostatic intolerance that is accompanied by an excessive increase in heart rate without arterial hypotension. We present two clinical reports of teenagers who were admitted in the Emergency Department with acrocyanosis and orthostatic intolerance. The first patient was 13-year-old and had an increase in heart rate of 40 bpm when moving from a reclining to a standing position. The second patient was 14-year-old and showed an increasing in heart rate up to 125 bpm after upright position. In both patients' blood pressure was normal and all investigations were negative. They were finally diagnosed with postural orthostatic tachycardia. Recognizing acrocyanosis as first sign of this disease is useful for diagnosis and can help to avoid unnecessary testing.

Temblor ortostático: una causa de mareo / Orthostatic tremor: a cause of dizziness

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Reduced Systolic Volume: Main Pathophysiological Mechanism in Patients with Orthostatic Intolerance? / Volume Sistólico Reduzido: Mecanismo Fisiopatológico Principal em Pacientes com Intolerância Ortostática?

Abstract Background: Orthostatic intolerance patients' pathophysiological mechanism is still obscure, contributing to the difficulty in their clinical management. Objective: To investigate hemodynamic changes during tilt test in individuals with orthostatic intolerance symptoms, including syncope or near syncope. Methods: Sixty-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. Results: In 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. Conclusion: Reduced 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.

Resumo Fundamento: O mecanismo fisiopatológico de pacientes com intolerância ortostática ainda é obscuro, contribuindo para a dificuldade no manejo clínicos desses pacientes. Objetivo: Investigar as alterações hemodinâmicas durante teste de inclinação (tilt teste) em indivíduos com sintomas de intolerância ortostática, incluindo síncope ou pré-síncope. Métodos: Sessenta e um pacientes, com tilt teste a 70º negativo na fase livre de vasodilatador, foram divididos em dois grupos. Para análise dos dados foram considerados apenas os primeiros 20 minutos de inclinação. Grupo I (33 pacientes) que tiveram elevação da resistência vascular periférica total (RVPT) durante posição ortostática e Grupo II (28 pacientes) com queda da RVPT (caracterizando insuficiência de resistência vascular periférica). O grupo controle consistia de indivíduos saudáveis e assintomáticos (24 indivíduos). Os parâmetros hemodinâmicos foram obtidos por um monitor hemodinâmico não invasivo em 3 momentos distintos (posição supina, tilt 10' e tilt 20'), ajustados para idade. Resultados: Na posição supina, o volume sistólico (VS) foi significantemente reduzido tanto no Grupo II quanto no I, quando comparado ao do Grupo controle, respectivamente (66,4 ±14,9 ml vs. 81,8±14,8 ml vs. 101,5±24,2 ml; p<0,05.) A RVPT, no entanto, foi mais elevada no Grupo II, quando comparada a do Grupo I e controles, respectivamente (1750,5± 442 dyne.s/cm5 vs.1424±404 dyne.s/cm5 vs. 974,4±230 dyne.s/cm5; p<0,05). Na posição ortostática, aos 10', houve repetição dos achados, com valores absolutos inferiores de VS Comparado aos controles (64,1±14,0 ml vs 65,5±11,3 ml vs 82,8±15,6 ml; p<0,05). A RVPT, todavia, apresentou queda relativa no Grupo II comparado ao I. Conclusão: Volume sistólico reduzido foi consistentemente observado nos grupos de pacientes com intolerância ortostática, quando comparado ao grupo controle. Foram observadas duas respostas distintas ao teste de inclinação: um grupo com elevação de RVPT e outro com queda relativa desta, indicando, possivelmente, falência mais acentuada dos mecanismos de compensação.

Initial circulatory response to active standing in Parkinson's disease without typical orthostatic hypotension / Resposta circulatoria inicial apos ortostatismo ativo na doenca de Parkinson sem hipotensao ortostatica tipica

While the circulatory response to orthostatic stress has been already evaluated in Parkinson's disease patients without typical orthostatic hypotension (PD-TOH), there is an initial response to the upright position which is uniquely associated with active standing (AS). We sought to assess this response and to compare it to that seen in young healthy controls (YHC). Method In 10 PD-TOH patients (8 males, 60±7 years, Hoehn and Yahr ≤3) the changes in systolic blood pressure (SBP) and heart rate that occur in the first 30 seconds (sec) of standing were examined. Both parameters were non-invasively and continuously monitored using the volume-clamp method by Peñáz and the Physiocal criteria by Wesseling. The choice of sample points was prompted by the results of previous studies. These sample points were compared to those of 10 YHC (8 males, 32±8 years). Results The main finding of the present investigation was an increased time between the AS onset and SBP overshoot in PD-TOH group (24±4 vs. 19±3 sec; p<0.05). Conclusion This delay might reflect a prolonged latency in the baroreflex-mediated vascular resistance response, but more studies are needed to confirm this preliminary hypothesis. .

Apesar da resposta circulatória ao estresse ortostático já foi estudada em pacientes com doença de Parkinson sem hipotensão ortostática típica (PD-TOH), não há uma resposta inicial que é exclusivamente associada com o ortostase ativa (AS). Portanto, buscou-se avaliar esta resposta e compará-la à observada em jovens saudáveis (YHC). Método Em 10 PD-TOH pacientes (8 homens, 60±7 anos, Hoehn e Yahr ≤3) as mudanças na pressão arterial sistólica (PAS) e da frequência cardíaca que ocorrem nos primeiros 30 segundos (seg) de pé foram examinados. Ambos parâmetros foram monitorizados continuamente através do método Peňáz e os critérios de Wesseling. Os pontos de amostragem foram escolhidos com base em estudos anteriores. Estes pontos foram comparados com os de 10 YHC (32±8 anos). Resultados O principal achado deste estudo foi o aumento do tempo entre o início de AS e rebote sistólica no grupo PD-TOH (24±4 vs 19±3 seg, p<0,05). Conclusão Este atraso pode refletir uma latência prolongada na resposta da resistência vascular mediado pelo barorreflexo, mas outros estudos são necessários para confirmar esta hipótese preliminar. .

Análise do sistema nervoso autônomo em idosos de acordo com apresença de intolerância ortostática e demência: um estudo pareado / Analysis of the autonomic nervous system in the elderly, according to the presence of of orthostatic intolerance and dementia: a paired study

Há estudos que demonstraram associação entre disfunção autonômica e demência, inclusive emcomparação com grupo controle. Já a análise espectral da frequência cardíaca entre idosos com e sem demência ecom intolerância ortostática (IO) não foi bem estudada, constituindo o principal objetivo desse trabalho. Método:Trata-se de estudo observacional, prospectivo, pareado por idade e sexo, com 54 pacientes sem tratamento ecom demência por doença de Alzheimer ou demência mista e 34 sem demência e com história de hipotensãopostural e/ou resposta vasodepressora. Os pacientes foram submetidos a avaliação clínica e monitoramento pelosistema Holter digital pela transformada de Fourier, na posição supina e depois em ortostatismo, durante 10minutos em cada posição. Resultados: 51 pacientes eram mulheres, com idade média de 76,1 anos. ApresentaramIO nove pacientes com demência e 24 sem demência. Houve diminuição do componente AF (alta frequência)(p=0,02, Wilcoxon) e aumento do BF/AF (BF: baixa frequência) (p=0,00) em toda a casuística com ortostatismo.Não houve diferença estatística entre os pacientes com e sem demência em relação a pressão arterial e análiseespectral (ambas obtidas na posição supina) e análise espectral em ortostatismo. Entre os pacientes sem e comIO, na posição supina, o BF foi de 400,7 e 364,8 ms2, respectivamente (p=0,00) e o AF foi de 1119,3 e 551,8ms2, (p=0,05; teste de Mann-Whitney), sem influência de sexo, idade, pressão arterial e frequência cardíaca naposição supina e uso de betabloqueador ou presença de diabetes. Não houve diferença na análise espectral entreos grupos com e sem IO durante o ortostatismo. Conclusões: Os menores valores dos componentes BF e AFforam observados em pacientes com intolerância ortostática na posição supina, sem influência do diagnóstico dedemência. Apesar do quadro de intolerância ortostática, pacientes idosos, com ou sem demência, demonstraramativação simpático-vagal com o ortostatismo.

Studies have shown an association between autonomic dysfunction and dementia, including controlgroup comparisons. Spectral analysis of heart rate among elderly with and without dementia and with orthostaticintolerance (OI) has not been well studied and is the main objective of this work. Methods: This prospective,observational study, paired by age and gender, which included 54 patients (pts) with dementia without treatment(by Alzheimer’s disease or mixed dementia) and 34 pts without dementia and with history of postural hypotensionand/or vasodepressor response. Pts underwent clinical evaluation and the digital Holter monitoring by Fourier transformation, in the supine position and after standing upright for 10 min in each position. Results: mean agewas 76.1 years, 51 women. Nine pts with dementia and 24 pts without dementia had OI. There was a decrease inthe HF (high frequency) component (p=0.02, Wilcoxon) and increased LF/HF (LF: low frequency) (p=0.00) inthe entire sample in standing position. There was no statistical difference between pts with and without dementiaon blood pressure and spectral analysis (both in supine position) and spectral analysis in standing position. Amongpts without and with OI in the supine position, LF was 400.7 and 364.8 ms2, respectively, p=0.00; and the HFwas 1119.3 and 551.8 ms2, p=0.05 (Mann-Whitney test), no influence of gender, age, blood pressure and heartrate in supine position and use of beta-blocker or presence of diabetes. There was no difference in spectral analysisbetween groups without and with OI during standing. Conclusions: There were lower LF and HF values in ptswith orthostatic intolerance in supine position without influence of the diagnosis of dementia. Despite the pictureof orthostatic intolerance, elderly patients, with or without dementia, showed sympathetic and vagal activationwith standing.

Hay estudios que han demostrado asociación entre la disfunción autonómica y la demencia, inclusoen comparación con grupo control. El análisis espectral de la frecuencia cardiaca entre ancianos con y sin demenciay con intolerancia ortostática (IO) no ha sido bien estudiado, constituyéndose el principal objetivo de este trabajo. Métodos: Se trata de estudio observacional, prospectivo, pareado por edad y sexo, compuesto de 54 pacientes(pts) con demencia sin tratamiento (por enfermedad de Alzheimer o demencia mixta) y 34 pts sin demencia y conhistoria de hipotensión postural y/o respuesta vasodepresora. Los pts fueron sometidos a la evaluación clínica y elmonitoreo por sistema Holter digital por transformada de Fourier, en la posición supina y luego en ortostatismo,durante 10 min. en cada posición.Resultados: La edad media de los pts fue de 76,1 años, 51 mujeres. PresentaronIO nueve pts con demencia y 24 pts sin demencia. Hubo disminución del componente AF (alta frecuencia)(p=0,02, Wilcoxon) y aumento del BF/AF (BF: baja frecuencia) (p=0,00) en toda la casuística con el ortostatismo.No hubo diferencia estadística entre pts con y sin demencia con relación a la presión arterial y el análisis espectral(ambos en la posición supina) y el análisis espectral en ortostatismo. Entre pts sin y con IO, en la posición supina,BF fue de 400,7 y 364,8 ms2, respectivamente, p=0,00; y el AF fue de 1119,3 y 551,8 ms2, p=0,05 (prueba deMann-Whitney), sin influencia de sexo, edad, presión arterial y frecuencia cardiaca en la posición supina y empleode betabloqueador o presencia de diabetes. No hubo diferencia en el análisis espectral entre los grupos sin y con IOdurante el ortostatismo.Conclusiones: Hubo menores valores de los componentes BF y AF en pts con intoleranciaortostática en la posición supina, sin influencia del diagnóstico de demencia. A pesar del cuadro de intoleranciaortostática, los pacientes ancianos, con o sin demencia, demostraron activación simpático-vagal.

Síndrome de platipnea-ortodeoxia / Platypnea-orthodeoxia syndrome

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