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

Authors

  • Bruno Laviolle,

    1. Inserm, CIC-P 0203 Clinical Investigation Centre, Rennes
    2. Rennes 1 University, Experimental & Clinical Pharmacology Laboratory, Rennes
    3. Rennes University Hospital, Department of Clinical Pharmacology, Rennes
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  • Erwan Donal,

    1. Inserm, CIC-IT 0804 Clinical Investigation Centre, Rennes
    2. Rennes University Hospital, Department of Cardiology, Rennes
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  • Pascale Le Maguet,

    1. Inserm, CIC-P 0203 Clinical Investigation Centre, Rennes
    2. Rennes University Hospital, Department of Surgical Intensive Care, Rennes
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  • Fabrice Lainé,

    1. Inserm, CIC-P 0203 Clinical Investigation Centre, Rennes
    2. Rennes University Hospital, Department of Clinical Investigation, Rennes, France
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  • Eric Bellissant

    Corresponding author
    1. Rennes 1 University, Experimental & Clinical Pharmacology Laboratory, Rennes
    2. Rennes University Hospital, Department of Clinical Pharmacology, Rennes
    • Inserm, CIC-P 0203 Clinical Investigation Centre, Rennes
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Correspondence

Professor Eric Bellissant, Service de Pharmacologie Clinique – CIC Inserm 0203. Hôpital de Pontchaillou, 2 Rue Henri Le Guilloux. 35033 Rennes cedex, France.

Tel.: +33 2 9928 3715

Fax: +33 2 9928 3716

E-mail: eric.bellissant@univ-rennes1.fr

Abstract

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.

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