• Matthew J Maiden, Marianne J Chapman, David J Torpy, Timothy R Kuchel, Iain J Clarke, Coralie H Nash, Jonathan D Fraser, and Guy L Ludbrook.
• 1Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. 2Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia. 3Department of Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. 4Preclinical, Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Adelaide, SA, Australia. 5Department of Physiology, Monash University, Clayton, VIC, Australia.
• Crit. Care Med. 2016 Jun 1; 44 (6): 1153-60.

ObjectivesTriiodothyronine 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.DesignRandomized blinded placebo-controlled trial.SettingPreclinical research laboratory.SubjectsThirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion.InterventionsTwo 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 ResultsPrimary 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.ConclusionsA 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.

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