Because of the possibility that one abnormal reading while standing might have been an erroneous reading, we dropped data from subjects with only one abnormal blood pressure or one eTCO2 value in the absence of orthostatic symptoms (4 controls and 5 CFS and 1 control and 3 CFS respectively). In addition, we excluded from further analysis data from 3 CFS patients with baseline end tidal C02 values ≥ 30 mmHg because they appeared to be chronic hyperventilators [17
]. Including the data from all these subjects would not have changed the overall results of this study. Finally two CFS patients on treatment for hypertension developed orthostatic hypotension, and so their data were also dropped. Following these exclusions, we analyzed the data from 62 CFS patients and 35 controls.
There was no significant difference in age between patients and controls (43.3 ± 10.5 [sd] years and 40.4 ± 7.9). Significantly more CFS patients than controls fulfilled our criteria for abnormal standing tests (53% vs 20%, p < .002). For both groups, abnormalities were mostly confined to one parameter – heart rate, blood pressure or end tidal CO2 (see Table ). 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; note that some subjects had more than one form of OI). However rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). The first occurrence of a hypocapnic value occurred in the first 3 minutes of standing for 8 of the 13 subjects. However, the magnitude of hypocapnia increased over time (see Figure ).
Rates of Normal and Different Abnormal Standing Tests
Figure 1 End tidal CO2 (mmHg) and time (min) before and after upright leaning. Data are presented as means ± sem over time. Subjects were in the supine position at -1 and 0 and then stood up, leaning their upper backs against a wall without moving their (more ...)
In an effort to evaluate possible variables producing orthostatic hypocapnia, we did a post-hoc analysis confined to CFS patients with orthostatic hypocapnia (n = 13) with two comparison groups – CFS patients with normal physiological responses to orthostatic challenge (n = 30) and healthy subjects with normal physiological responses to orthostatic challenge (n = 28).
There was no difference in rates of "severe CFS" between patients with orthostatic hypocapnia and patients with no orthostatic intolerance (38% vs 30%). There was no difference in the change in respiratory rates from supine to standing among groups; however both CFS groups tended to breath slower while supine than controls (orthostatic hypocapnia: 15.4 ± 1.4; no intolerance: 16.1 ± 0.6; controls: 18.5 ± 0.6; p = .052 and .06 for each comparison). There were no differences among the 3 groups for supine systolic/diastolic blood pressure or for heart rate while supine or for the magnitude of change when standing. During orthostatic challenge, end tidal CO2 values showed a small decline over time for the CFS group without orthostatic intolerance and the controls (F7,185.5
= 2.89, p < .001); this effect of orthostatic challenge on normals has been previously reported [18
Anxiety and illness ratings in the supine position were higher in both CFS groups than in the controls (p < .04 for comparisons on anxiety and < .001 on illness). Ratings of shortness of breath and dizziness in the supine position did not differ among groups.
Magnitude of change in anxiety did not differ among groups going from supine to standing. Magnitude of change in feeling ill ratings going from supine to standing increased for the CFS group with orthostatic hypocapnia but not for the other CFS group or the controls (F [Int]7,60.5 = 4.14; p < .001). Magnitude of change in shortness of breath going from supine to standing was significantly greater for the CFS group with orthostatic hypocapnia than the CFS group without orthostatic intolerance (F1,30.4 = 4.44, p < .05). Both CFS groups reported a greater increase in shortness of breath while standing compared to controls (p < .005 for both comparisons). In terms of increases in dizziness ratings going from supine to standing, it was the CFS group without orthostatic abnormalities that was higher than controls (F1,47.3 = 14.2, p < .001) with the CFS group with hypocapnia being intermediary.
There was no significant difference in depressed mood between the 2 CFS groups as assessed by the CES-D, but both were significantly higher than controls (p < .001; medians for those with orthostatic hypocapnia, no orthostatic intolerance and controls, respectively were 20.5, 19.5, 6.0).