Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure

Abstract

Treatment with head-up tilt sleeping and low-dose fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic blood pressure in patients with neurogenic orthostatic hypotension. The aim of the present study was to examine whether the improvement in orthostatic blood pressure during combined treatment with low-dose fludrocortisone and nocturnal head-up tilt in patients with neurogenic orthostatic hypotension can be attributed to expansion of plasma volume or to increased total peripheral resistance. The effects of a 3-week treatment with fludrocortisone and nocturnal head-up tilting on the postural changes in arterial pressure, heart rate, and cardiac output (pulse contour) were evaluated in eight consecutive patients with orthostatic hypotension. The period during which the patients were able to remain in the standing position without orthostatic complaints increased minimally from 3 to 10 minutes. The decrease in arterial pressure after 1 minute of standing--(means with standard deviations in parentheses) systolic, 49 (20) mm Hg; diastolic, 18 (11) mm Hg--before treatment was produced by a greater than normal decrease in cardiac output: 37% (10%) in patients with neurogenic orthostatic hypotension versus -14% (8%) in control subjects. Treatment increased upright arterial pressure from 83 (19) mm Hg systolic and 55 (13) mm Hg diastolic to 114 (22) mm Hg systolic and 60 (16) mm Hg diastolic by limiting the decrease in cardiac output. Body weight increased but hematocrit did not change. Leg pressure-volume relationship decreased in the two patients studied. The responses of plasma renin activity and aldosterone to orthostatic stress prior to treatment were subnormal and became even lower after treatment. The improvement in upright blood pressure in orthostatic hypotension during treatment with fludrocortisone and nocturnal head-up sleeping is the result of a reduction in the orthostatic decrease in cardiac output. Preliminary data suggest that the expanded body fluid volume is allocated to the perivascular space rather than to the intravascular space.

Orthostatic Tolerance, Cerebral Oxygenation, and Blood Velocity in Humans With Sympathetic Failure

“…In patients with sympathetic failure, the postural fall in arterial pressure is amplified by the larger orthostatic fall in CO ( Figure 1 and Table 2) because of enhanced venous pooling of blood, with an excessive reduction of venous return. 49,50 This is compatible with the tendency for higher values for thoracic electric impedance in symptomatic patients, suggesting a smaller central blood volume (Table 3). 29 In addition, the decrease in PETCO 2 on standing may have contributed to the cerebral hypoperfusion in the symptomatic patients.…”

“…49,54 There is no specific treatment for sympathetic vasomotor failure, and therapy should be focused on alleviating the patient's orthostatic tolerance and reducing the orthostatic fall in CO by increasing the circulating volume. 50,55 Figure 4. Magnitude and time course of orthostatic reduction in cerebral blood velocity and oxygenation.…”

Syncope

“…Pharmacological therapy: the alpha agonist midodrine (5-20 mg, three times daily) (24,25) reduces reflex syncope. Other medications include fludrocortisone, (26) a mineralocorticoid that expands fluid volume, and is widely used in adult patients with OH, despite weaker clinical evidence than for midodrine. There is no clinical evidence supporting the use of B-blockers (27) or paroxetine.…”

Drug therapies in older adults (part 2)

“…It is thought to raise blood pressure by promoting the renal retention of sodium and increasing plasma volume. 16 However, persistent exposure may lead to the normalisation of both the plasma volume and the degree of sodium retention; despite this, a sustained increase in blood pressure is observed. 17 This suggests that fl udrocortisone may sensitise the α-adrenergic receptors of blood vessels, leading to an indiscriminate increase in peripheral vascular resistance and a risk of supine hypertension, 17 in addition to the more frequent adverse effects of dependent oedema, hypokalemia, headaches and congestive heart failure (HF).…”

“…In the fi rst instance, six patients were studied (mean age: 52 years; range: 23-65 years), in the second, eight (mean age: 50 years; range: 23-65 years). 20,21 While both studies suggest that fl udrocortisone may help some younger patients with OH, the absence of older adults is notable. 20,21 Whether such a bias exists in the doubleblind trial published in German is unclear (n=60); the study also reported haemodynamic benefi ts and improved symptom control among those receiving fl udrocortisone.…”