Low doses of fludrocortisone and hydrocortisone, alone or in combination, on vascular responsiveness to phenylephrine in healthy volunteers

• Published in: British journal of clinical pharmacology Vol. 75; no. 2; pp. 423 - 430
• Main Authors: Laviolle, Bruno, Donal, Erwan, Le Maguet, Pascale, Lainé, Fabrice, Bellissant, Eric
• Format: Journal Article
• Language: English
• Published: England Wiley 01.02.2013; Blackwell Science Inc
• Subjects: Administration, Oral; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Bioengineering; Blood Pressure; Blood Pressure - drug effects; Cardiology and cardiovascular system; Computer Science; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Interactions; Engineering Sciences; Fludrocortisone; Fludrocortisone - administration & dosage; Fludrocortisone - pharmacology; glucocorticoids; haemodynamics; Heart Rate; Heart Rate - drug effects; Human health and pathology; Humans; Hydrocortisone; Hydrocortisone - administration & dosage; Hydrocortisone - pharmacology; Infusions, Intravenous; Injections, Intravenous; Life Sciences; Male; mineralocorticoids; Pharmacodynamics; Phenylephrine; Phenylephrine - therapeutic use; Shock, Septic; Shock, Septic - drug therapy; Signal and Image processing; Vasoconstrictor Agents; Vasoconstrictor Agents - therapeutic use; Young Adult; glucocorticoids; hydrocortisone; mineralocorticoids; haemodynamics; fludrocortisone
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2012.04359.x

Aims 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.