Faculty Collaboration Database

Inhibition of the adrenocorticotropin response to surgery in humans: interaction between dexamethasone and fentanyl. J Clin Endocrinol Metab 1987 Aug;65(2):295-8

Date

08/01/1987

Pubmed ID

3036903

DOI

10.1210/jcem-65-2-295

Scopus ID

2-s2.0-0023278713 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

We examined the plasma ACTH and cortisol responses to surgery in 25 patients with atherosclerotic heart disease undergoing myocardial revascularization. The patients were all premedicated with diazepam, and general anesthesia was induced with thiopental. They were randomly assigned to one of four groups: I) no dexamethasone (DEX), enflurane anesthesia, II) 40 mg DEX, iv, 45-60 min before sternotomy, enflurane anesthesia, III) no DEX, fentanyl [N-(1-phenethyl-4-piperidyl)propionanilide] anesthesia (50-100 micrograms/kg), and IV) DEX, fentanyl anesthesia. Isokalemic hemodilution of significant magnitude occurred during cardiopulmonary bypass. All groups had significant increases in plasma ACTH during surgery, which returned to control levels 22 h after the bypass. Group I (no DEX, no fentanyl) and group III (no DEX, fentanyl) patients had large similar increases in plasma ACTH, which peaked 2-4 h postbypass [400 +/- 83 (+/- SEM) pg/mL; 88 +/- 18 pmol/L]. The group II (DEX, no fentanyl) patients also had large increases in ACTH which were similar to those in groups I and III, except 2-4 h postbypass (183 +/- 91 pg/mL; 40 +/- 20 pmol/L). The group IV (DEX, fentanyl) patients had a significantly attenuated ACTH response to surgery; the mean plasma ACTH level 2-4 h postbypass was only 54 +/- 21 pg/mL (12 +/- 5 pmol/L). Therefore, although DEX or fentanyl alone had a minimal effect on the ACTH response to surgery, a significant attenuation occurred when DEX and fentanyl were used in combination. We conclude that glucocorticoids and morphine agonists exert interactive inhibitory effects on ACTH release in humans, probably by virtue of their suppression of CRH release from the hypothalamus.

Author List

Raff H, Norton AJ, Flemma RJ, Findling JW

Authors

James W. Findling MD Professor in the Medicine department at Medical College of Wisconsin
Hershel Raff PhD Professor in the Academic Affairs department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenocorticotropic Hormone
Aged
Cardiopulmonary Bypass
Coronary Artery Disease
Dexamethasone
Drug Interactions
Female
Fentanyl
Humans
Hydrocortisone
Male
Middle Aged
Myocardial Revascularization
Random Allocation
Sternum