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Septic shock may be associated with a loss in cardiovascular variability and adrenal dysfunction.To investigate the relationship between cardiovascular autonomic modulation and adrenal function during sepsis.Seventy-five volunteers with septic shock and six healthy volunteers were prospectively included in the study. Cardiovascular variability was assessed by spectral analysis of heart rate and diastolic blood pressure signals, which included computation of normalized low (LFnu) and high frequency (HFnu) components. Cardiovascular variability was investigated in patients and healthy volunteers immediately before and 1 hr after a single bolus of 50 mg of hydrocortisone (study phase I); in patients according to adrenal function (study phase II); and in patients with septic shock and adrenal insufficiency, before and 72 hrs after a treatment with 50 mg every 6 hrs of hydrocortisone and 50 μg daily of fludrocortisone or their placebos (study phase III). As compared to healthy volunteers, patients had decreased LFnu-HR (.16 ± .05 vs. .23 ± .07 p = .01) and LFnu-DBP (.18 ± .11 vs. .28 ± .02 p = .01) and, after hydrocortisone, they had a greater increase in LFnu-DBP (p = .01). As compared to patients with normal adrenal function, those with adrenal failure had decreased LFnu-HR (.1 ± .01 vs. .2 ± .15 p = .01) and LFnu-DBP (.008 ± .01 vs. .14 ± .22 p = .0003). In patients with adrenal failure, as compared to placebos, hydrocortisone plus fludrocortisone increased significantly LFnu-DBP (p = .02) and low frequency/high volume ratio (p = .009).In septic shock, the loss in cardiovascular variability is more marked in patients with adrenal insufficiency and is partly restored by exogenous administration of corticosteroids.