Perioperative Glucocorticoid Therapy for Patients with Adrenal Insufficiency: Dosing Based on Pharmacokinetic Data

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 3; pp. e753 - e761
• Main Author: Arafah, Baha M
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-03-2020
• Subjects: Adrenal Insufficiency - drug therapy; Adrenal Insufficiency - pathology; Adrenal Insufficiency - surgery; Adult; Aged; Biomarkers - analysis; Biomarkers - metabolism; Case-Control Studies; Dexamethasone; Dosage; Female; Follow-Up Studies; Glucocorticoids; Glucocorticoids - pharmacokinetics; Glucocorticoids - pharmacology; Hormones; Humans; Hydrocortisone; Hydrocortisone - analysis; Hydrocortisone - metabolism; Intubation; Male; Middle Aged; Pharmacokinetics; Postoperative Period; Prognosis; Supplements; Surgery; Tissue Distribution; stress doses of glucocorticoids; adrenal insufficiency; HPA function
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa042

Abstract
Background
Perioperative glucocorticoid therapy for patients with adrenal insufficiency (AI) is currently based on anecdotal reports, without supporting pharmacokinetic data.
Methods
We determined the half-life, clearance, and volume of distribution of 2 consecutive intravenously (IV)-administered doses of hydrocortisone (15 or 25 mg every 6 hours) to 22 dexamethasone-suppressed healthy individuals and used the data to develop a novel protocol to treat 68 patients with AI who required surgical procedures. Patients received 20 mg of hydrocortisone orally 2 to 4 hours before intubation and were started on 25 mg of IV hydrocortisone every 6 hours for 24 hours and 15 mg every 6 hours during the second day. Nadir cortisol concentrations were repeatedly measured during that period.
Results
In healthy individuals, cortisol half-life was longer when the higher hydrocortisone dose was administered (2.02 ± 0.15 vs 1.81 ± 0.11 hours; P < 0.01), and in patients with AI, the half-life was longer than in healthy individuals given the same hydrocortisone dose. In both populations, the cortisol half-life increased further with the second hormone injection. Prolongation of cortisol half-life was due to decreased hydrocortisone clearance and an increase in its volume of distribution. Nadir cortisol levels determined throughout the 48 postoperative hours were within the range of values and often exceeded those observed perioperatively in patients without adrenal dysfunction.
Conclusions
Cortisol pharmacokinetics are altered in the postoperative period and indicate that lower doses of hydrocortisone can be safely administered to patients with AI undergoing major surgery. The findings of this investigation call into question the current practice of administering excessive glucocorticoid supplementation during stress.