Tag: hypocapnia

Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome

Abstract:

Background: The autonomic nervous system (ANS) is a complex network where sympathetic and parasympathetic domains interact inside and outside of the network. Correlation-based network analysis (NA) is a novel approach enabling the quantification of these interactions. The aim of this study is to assess the applicability of NA to assess relationships between autonomic, sensory, respiratory, cerebrovascular, and inflammatory markers on post-acute sequela of COVID-19 (PASC) and postural tachycardia syndrome (POTS).

Methods: In this retrospective study, datasets from PASC (n = 15), POTS (n = 15), and matched controls (n = 11) were analyzed. Networks were constructed from surveys (autonomic and sensory), autonomic tests (deep breathing, Valsalva maneuver, tilt, and sudomotor test) results using heart rate, blood pressure, cerebral blood flow velocity (CBFv), capnography, skin biopsies for assessment of small fiber neuropathy (SFN), and various inflammatory markers. Networks were characterized by clusters and centrality metrics.

Results: Standard analysis showed widespread abnormalities including reduced orthostatic CBFv in 100%/88% (PASC/POTS), SFN 77%/88%, mild-to-moderate dysautonomia 100%/100%, hypocapnia 87%/100%, and elevated inflammatory markers. NA showed different signatures for both disorders with centrality metrics of vascular and inflammatory variables playing prominent roles in differentiating PASC from POTS.

Conclusions: NA is suitable for a relationship analysis between autonomic and nonautonomic components. Our preliminary analyses indicate that NA can expand the value of autonomic testing and provide new insight into the functioning of the ANS and related systems in complex disease processes such as PASC and POTS.

Source: Novak P, Giannetti MP, Weller E, Hamilton MJ, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM, Castells M. Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome. Neurol Sci. 2022 Sep 28:1–12. doi: 10.1007/s10072-022-06423-y. Epub ahead of print. PMID: 36169757; PMCID: PMC9517969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517969/ (Full text)

Physiological assessment of orthostatic intolerance in chronic fatigue syndrome

Abstract:

Background: Orthostatic intolerance-OI is common in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-ME/CFS. We used a 10-min passive vertical lean test as orthostatic challenge-OC and measured changes in vitals and end tidal CO2 (eTCO2). An abnormal physiologic response to OC was identified in 60% of the 63 patients evaluated from one to three times over several years. Hypocapnia, either resting or induced by OC, was the most frequent abnormality, followed by postural orthostatic tachycardia.

Objective: Evaluate the physiologic response of patients with ME/CFS to a standardized OC.

Design: Respiratory and heart rate, blood pressure and eTCO2 were recorded twice at the end of 10-min supine rest and then every minute during the 10-min lean. Hypocapnia was eTCO2 ≤ 32 mmHg. Orthostatic tachycardia was heart rate increase ≥ 30 beats per minute compared with resting or ≥ 120 BPM. Orthostatic hypotension was decreased systolic pressure ≥ 20 mmHg from baseline. Tachypnea was respiratory rate of ≥ 20 breaths per minute-either supine or leaning. Questionnaire data on symptom severity, quality of life and mood were collected at visit #2.

Patients: 63 consecutive patients fulfilling the 1994 case definition for CFS underwent lean testing at first visit and then annually at visit 2 (n = 48) and 3 (n = 29).

Measures: Supine hypocapnia; orthostatic tachycardia, hypocapnia or hypotension.

Results: The majority of ME/CFS patients (60.3%, 38/63) had an abnormality detected during a lean test at any visit (51%, 50% and 45% at visits 1, 2 and 3, respectively). Hypocapnia at rest or induced by OC was more common and more likely to persist than postural orthostatic tachycardia. Anxiety scores did not differ between those with and without hypocapnia.

Conclusions: The 10-min lean test is useful in evaluation of OI in patients with ME/CFS. The most frequent abnormality, hypocapnia, would be missed without capnography.

Source: Natelson BH, Lin JS, Blate M, Khan S, Chen Y, Unger ER. Physiological assessment of orthostatic intolerance in chronic fatigue syndrome. J Transl Med. 2022 Feb 16;20(1):95. doi: 10.1186/s12967-022-03289-8. PMID: 35172863. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03289-8 (Full study)

Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post–Coronavirus Disease

Abstract:

Objectives: The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Background: Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom.

Methods: The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO2), slope of minute ventilation to CO2 production (VE/VCO2 slope), and end tidal pressure of CO2 (PetCO2) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing.

Results: Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO2 averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO2). VE/VCO2 slope was 30 ± 7. PetCO2 at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO2 <80% predicted. All patients with peak VO2 <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO2 had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO2 (n = 17), and/or hypocapnia PetCO2 <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS.

Conclusions: Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.

Source: Mancini DM, Brunjes DL, Lala A, Trivieri MG, Contreras JP, Natelson BH. Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease. JACC Heart Fail. 2021 Dec;9(12):927-937. doi: 10.1016/j.jchf.2021.10.002. PMID: 34857177; PMCID: PMC8629098. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629098/ (Full text)

Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) with orthostatic intolerance is characterized by neurocognitive deficits and impaired working memory, concentration, and information processing. In CFS, upright tilting [head-up tilt (HUT)] caused decreased cerebral blood flow velocity (CBFv) related to hyperventilation/hypocapnia and impaired cerebral autoregulation; increasing orthostatic stress resulted in decreased neurocognition.

We loaded the baroreflex with phenylephrine to prevent hyperventilation and performed n-back neurocognition testing in 11 control subjects and 15 CFS patients. HUT caused a significant increase in 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 decrease in end-tidal CO2 (ETCO2; 42.8 ± 1.2 vs. 33.9 ± 1.1 Torr, P < 0.05) in CFS vs. control. HUT caused CBFv to decrease 8.7% in control subjects but fell 22.5% in CFS.

In CFS, phenylephrine prevented the HUT-induced hyperventilation/hypocapnia and the significant drop in CBFv with HUT (-8.1% vs. -22.5% untreated). There was no difference in control subject n-back normalized response time (nRT) comparing supine to HUT (106.1 ± 6.9 vs. 97.6 ± 7.1 ms at n = 4), and no difference comparing control to CFS while supine (97.1 ± 7.1 vs 96.5 ± 3.9 ms at n = 4). However, HUT of CFS subjects caused a significant increase in nRT (148.0 ± 9.3 vs. 96.4 ± 6.0 ms at n = 4) compared with supine.

Phenylephrine significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (114.6 ± 7.1 vs. 114.6 ± 9.3 ms at n = 4). Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions. Increasing blood pressure with phenylephrine can alter CBFv. In CFS subjects, mitigation of the HUT-induced CBFv decrease with phenylephrine has a beneficial effect on n-back outcome.

Copyright © 2014 the American Physiological Society.

 

Source: Medow MS, Sood S, Messer Z, Dzogbeta S, Terilli C, Stewart JM. Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome. J Appl Physiol (1985). 2014 Nov 15;117(10):1157-64. doi: 10.1152/japplphysiol.00527.2014. Epub 2014 Oct 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233252/ (Full article)

 

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements.

Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p&lt;0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea.

In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p&lt;0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness.

In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

 

Source: Ravindran M, Adewuyi O, Zheng Y, Rayhan RU, Le U, Timbol C, Merck S, Esteitie R, Read C, Cooney M, Baraniuk J. Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies. Glob J Health Sci. 2012 Dec 12;5(2):94-110. doi: 10.5539/gjhs.v5n2p94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209305/ (Full article)

 

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

Abstract:

CONTEXT: Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

OBJECTIVE: To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

DESIGN: Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

SETTING: Referral practice and research center.

PARTICIPANTS: 60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

MAIN OUTCOME MEASURES: Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

RESULTS: CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

CONCLUSION: A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

 

Source: Natelson BH, Intriligator R, Cherniack NS, Chandler HK, Stewart JM. Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome. Dyn Med. 2007 Jan 30;6:2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796865/ (Full article)

 

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope

Abstract:

OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF).

PATIENTS AND METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation.

RESULTS: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients.

CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

 

Source: Naschitz JE, Mussafia-Priselac R, Kovalev Y, Zaigraykin N, Slobodin G, Elias N, Rosner I. Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope. Am J Med Sci. 2006 Jun;331(6):295-303. https://www.ncbi.nlm.nih.gov/pubmed/16775435

 

Brainstem hypoperfusion in CFS

Comment on: Brainstem perfusion is impaired in chronic fatigue syndrome. [QJM. 1995]

 

Sir, Costa and his colleagues {QJ Med 1995; 88:767-73) are to be congratulated for providing more information about chronic fatigue syndrome. Hypocapnia is a powerful and readily available cerebral vasoconstrictor.1

The ‘cerebral vasoconstriction, and reduction in cerebral blood flow, are initiated when the arterial pCO2 has fallen 2 mmHg below normal. When the pCO2 has fallen by 25 mmHg, cerebral blood flow is decreased by about one third … the maximum possible reduction of blood flow that can be achieved by respiratory alkalaemia is of the order of 40 per cent’.2

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/89/2/163.1.long

 

Source: Nixon PG. Brainstem hypoperfusion in CFS. QJM. 1996 Feb;89(2):163-4. http://qjmed.oxfordjournals.org/content/89/2/163.1.long

 

Hyperventilation disorders

Hyperventilation syndrome falls into the shadowy hinterland between physiology, psychiatry, psychology and medicine. In this respect it joins a long list of syndromes from the past of which effort syndrome is just one example. Myalgic encephalomyelitis (ME) and postviral fatigue syndrome are recent attempts to impose a unitary definition on what is probably a complex interaction between many different organic and psychological factors. The recent introduction of terms such as somatization disorder recognize this aetiological heterogeneity (1).

The symptoms of hypocapnia induced by voluntary overbreathing were first described by Haldane in 1908, the first case of spontaneous hyperventilation by Goldman in 1922 (2), and the term Hyperventilation Syndrome was first used by Dalton, Kerr and Gliebe in 1937 to describe patients with symptoms both of hypocapnia and anxiety (3). Since then, many different interpretations of this term have appeared in the literature encompassing patients with widely different aetiologies. Much research in this area is bedevilled by failure to define clearly the detailed characteristics of the patients studied; by the assumption of definitions for which there is no universal agreement; and by the presentation of scientifically unsound data lacking in rigorous quantitative proof and with perpetuation of circular arguments. The papers in this issue of the journal make a commendable attempt to reintroduce the reader to the historical perspectives of this subject and to clarify some of the issues, but unfortunately also have some of the shortcomings common to so many of the studies in this very difficult field.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292944/pdf/jrsocmed00129-0005.pdf

 

Source: Gardner W. Hyperventilation disorders. J R Soc Med. 1990 Dec;83(12):755-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292944/

 

Aerobic work capacity in chronic fatigue syndrome

Comment on Aerobic work capacity in patients with chronic fatigue syndrome. [BMJ. 1990]

SIR,

The data of Dr Marshall S Riley and colleagues (1) are consistent with our findings (2) that most patients referred with the chronic fatigue syndrome have the effort syndrome-that is, chronic hyperventilation as a consequence of excessive effort and distress.(3)

May we draw attention to three points. Dr Riley and colleagues concluded that the patients could not be hyperventilating because their values of end-tidal partial pressure of carbon dioxide at rest and at peak exercise did not differ significantly from those of the controls.

In our opinion the values published for the controls (35 8 mmHg at rest and 36-3 mmHg at peak exercise) are too low to be accepted as normal. The finding that the patients reached their anaerobic threshold far quicker than did the controls is consistent with the early acidosis on exertion known to occur in chronic hyperventilation. This is a consequence of the depletion of the body’s buffer base reserves,(4) brought about by renal compensation for chronic respiratory alkalosis.(5)

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664329/pdf/bmj00207-0055b.pdf

 

Source: Rosen SD, King JC, Wilkinson JB, Nixon PG. Aerobic work capacity in chronic fatigue syndrome. BMJ. 1990 Nov 24;301(6762):1217. [Comment] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664329/