“Physiological assessment of orthostatic intolerance in chronic fatigue syndrome”: Links And Excerpts

Today I link to and excerpt from Physiological assessment of orthostatic intolerance in chronic fatigue syndrome [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Benjamin H Natelson 1, Jin-Mann S Lin 2, Michelle Blate 3, Sarah Khan 3, Yang Chen 2, Elizabeth R Unger 2. J Transl Med. 2022 Feb 16;20(1):95. doi: 10.1186/s12967-022-03289-8.

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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.


Myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS] is a medically unexplained illness characterized by fatigue severe enough to produce a substantial decrease in activity. In addition, in its 2015 review of the known science regarding this disorder, the Institute of Medicine recommended the clinical case defnition include unrefreshing sleep and post-exertional malaise (minimal exertion producing subsequent, often delayed
syndromic worsening) along with either cognitive problems or orthostatic intolerance [1]. The latter symptom is described by the patient as a worsening of symptoms or dizziness while standing or sitting upright.

Orthostatic intolerance [OI] often refects altered autonomic activity and may be evaluated by measuring heart rate and blood pressure during a 10-min period of passive vertical leaning (the “lean test”). Two commonly reported abnormalities are orthostatic hypotension and postural orthostatic tachycardia syndrome (POTS). However, adding capnography to the measures in the lean test will allow detection of the postural orthostatic syndrome of hypocapnia [POSH], another important cause of orthostatic intolerance. Both POTS and POSH have been recognized for some time [2, 3], and we have found POSH to occur more frequently than any of the other
abnormalities [4]. Even in the absence of an orthostatic challenge (i.e., while seated or supine), persons with ME/CFS have been reported to have signifcantly lower measures of end tidal CO2 than healthy controls [5–7].


The study includes 63 consecutive patients who were evaluated and met criteria for chronic fatigue syndrome at the Pain & Fatigue Study Center, Mount Sinai Beth Israel in New York City between 2012 and 2015. . . . Patients were also evaluated to determine if they fulflled case defnitions for fbromyalgia [FM],
irritable bowel syndrome [IBS] and multiple chemical sensitivity [MCS] using accepted criteria as previously described [9].

The lean test was performed using a protocol developed by NASA [10]. Specifcally, after at least 10 min lying supine, baseline physiological measures—blood pressure, heart and respiratory rates and end tidal CO2 [eTCO2] as assessed using an Oridion Microstream Capnograph (Medtronics, Inc., Minneapolis, MN)—were recorded twice, a minute apart. Patients were then asked to stand with legs together approximately 6–8 inches from a wall and then to lean for 10 min while physiological measurements were taken every minute. The lean test was repeated at visits of 8 to 15-month
intervals for up to three visits.



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