PubMed · 13437787
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E L SCHAFER. 1957-04-26. [9-alpha-fluorhydrocortisone].. https://doi.org/10.1055/s-0028-1114757
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BACKGROUND: Neurally mediated syncope is a common and frequently distressing problem. It is associated with a poor quality of life, which improves when the frequency of syncope is reduced. Few therapies for neurally mediated syncope have been proven effective. Fludrocortisone is commonly used to prevent recurrences of syncope but with little evidence to support its use. A placebo-controlled clinical trial of fludrocortisone for the prevention of neurally mediated syncope is needed. STRUCTURE OF STUDY: POST II is a multicenter, international, randomized, placebo-controlled study of fludrocortisone in the prevention of neurally mediated syncope. The primary end point is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive fludrocortisone 0.05 to 0.2 mg or matching placebo and followed for 1 year. Secondary end points include syncope frequency, presyncope, and quality of life. Primary analysis will be performed with an intention-to-treat approach, with a secondary on-treatment analysis. POWER CALCULATIONS: Assuming a 40% risk of syncope in the control arm, a relative reduction of 40% by fludrocortisone, and a dropout rate of 20%, the enrollment of 310 patients will give an 80% power of reaching a positive conclusion about fludrocortisone therapy, with P = .05. REGISTRATION: POST II is registered with both (ISRCTN 51802652) and (NCT00118482). IMPLICATIONS: This study will be the first adequately powered trial to determine whether fludrocortisone is effective in preventing neurally mediated syncope. If it is effective, then fludrocortisone may become the first-line medical therapy for this condition.
Hyponatremia, natriuresis, and a decrease in plasma volume of greater than 10% occurs in approximately 50% of the patients with aneurysmal SAH, perhaps due to SIADH and CSWS. However, fluid restriction, as indicated in SIADH, might result in vasospasm and cerebral infarction in these patients. Maintaining intravascular volume seems to be important in SAH; several reports suggest that cerebral ischemia can be reversed by use of volume expanders. Fludrocortisone has been shown to reduce natriuresis, which may help maintain plasma volume in patients with SAH. Adequate oral salt intake also appears to have possible therapeutic benefit in these patients. However, it remains unproven whether fludrocortisone results in a decreased incidence of cerebral ischemia. Larger controlled trials are needed to ascertain the impact of fludrocortisone on prevention of cerebral ischemia in patients with SAH.
Fludrocortisone has been a mainstay of therapy for orthostatic hypotension for many years. Clinical experience suggests that there exists a substantial interindividual variation in responsiveness to the drug. To assess this, we have developed an assay that permits measurement of the low concentrations of fludrocortisone found in human plasma. Fludrocortisone was detected by radioimmunoassay. A polyclonal rabbit antibody, raised against dexamethasone which cross-reacts strongly with fludrocortisone, was reacted with either standard or unknown samples in the presence of [125I]fludrocortisone-3-TyrNH2 (synthesized by coupling tyrosine amide to fludrocortisone-3-oxime and iodinating with chloramine T oxidation). The ED10, ED50, and ED80 were 0.34, 5.0, and 30 ng/mL of plasma, respectively. The cross reactivity with other 9-fluorinated steroids was found as follows: dexamethasone, 340%; betamethasone, 230%; and triamicinolone, 8%. To preclude an erroneous result, subjects who were pregnant or receiving any steroid medication were excluded from the study. The percent cross-reactivity with the main naturally occurring steroids was as follows: 11-desoxycortisol 3.2%, cortisol 1.1%, DOC 0.3%, pregnenolone 0.1%, corticosterone 0.06%, progesterone 0.05%, and aldosterone < 0.05%. The only compound with potential for interference, because of its high level in the circulation in the early morning, was cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)