Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial

• Published in: Critical care medicine Vol. 44; no. 6; pp. 1153 - 1160
• Main Authors: Maiden, Matthew J., Chapman, Marianne J., Torpy, David J., Kuchel, Timothy R., Clarke, Iain J., Nash, Coralie H., Fraser, Jonathan D., Ludbrook, Guy L.
• Format: Journal Article
• Language: English
• Published: United States by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc 01-06-2016; Copyright by by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Arterial Pressure - drug effects; Disease Models, Animal; Drug Therapy, Combination; Female; Hydrocortisone - pharmacology; Infusions, Intravenous; Norepinephrine - administration & dosage; Random Allocation; Sheep; Shock, Septic - drug therapy; Shock, Septic - physiopathology; Single-Blind Method; Triiodothyronine - blood; Triiodothyronine - pharmacology
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/CCM.0000000000001644

OBJECTIVES:Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock.
DESIGN:Randomized blinded placebo-controlled trial.
SETTING:Preclinical research laboratory.
SUBJECTS:Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion.
INTERVENTIONS:Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone.
MEASUREMENTS AND MAIN RESULTS:Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function.
CONCLUSIONS:A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.