Low doses of fludrocortisone and hydrocortisone, alone or in combination, on vascular responsiveness to phenylephrine in healthy volunteers.
OBJECTIVE
A single administration of hydrocortisone has been shown to enhance the pressor response to phenylephrine in healthy volunteers and to norepinephrine in septic shock patients. Similar data do not exist for fludrocortisone. Since there continues to be disagreement about the utility of fludrocortisone in septic shock, we assessed the effects of a single administration of low doses of hydrocortisone (50 mg intravenously) and fludrocortisone (50 μg orally), given either alone or in combination, on phenylephrine mean arterial pressure and cardiac systolic and diastolic function dose-response relationships in 12 healthy male volunteers with hypo-aldosteronism induced by intravenous sodium loading.


METHODS
This was a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 × 2 factorial design. Subjects received first a 2000 ml infusion of NaCl 0.9% during 2 h. Then fludrocortisone 50 μg (or its placebo) was administered orally and hydrocortisone 50 mg (or its placebo) was injected intravenously. At 1.5 h after treatment administration, incremental doses of phenylephrine were infused (from 0.01 to 3 μg kg(-1) min(-1)), each dose being infused during 5 min.


RESULTS
Both fludrocortisone (P < 0.001) and hydrocortisone (P = 0.002) induced a significant decrease in pressor response to phenylephrine, their effects being additive (fludrocortisone × hydrocortisone interaction, P = 0.792). The two drugs did not induce any detectable cardiac effect.


CONCLUSIONS
Single administrations of fludrocortisone and hydrocortisone decreased the pressor response to phenylephrine in healthy volunteers with hypo-aldosteronism. These similar effects of hydrocortisone and fludrocortisone probably express a rapid non-genomic vasodilating effect of the two steroids in the context of acute volume loading.
Inserm, CIC-P 0203 Clinical Investigation Centre, Rennes, France.
Bruno
B
Laviolle
Erwan
E
Donal
Pascale
P
Le Maguet
Fabrice
F
Lainé
Eric
E
Bellissant
D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D005438:Fludrocortisone / Q000008:administration & dosage* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000494:pharmacology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D010656:Phenylephrine / Q000627:therapeutic use*; D012772:Shock, Septic / Q000188:drug therapy; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D005438:Fludrocortisone; D006854:Hydrocortisone