Effects of Thyroid Hormone Treatment on Diaphragmatic Efficiency in Subjects With Nonthyroidal Illness Syndrome and on Ventilation

BACKGROUND: Several respiratory abnormalities can be present in primary hypothyroidism and can be reversed with adequate hormone treatment. However, the role of thyroid hormone replacement therapy on the respiratory system in patients with nonthyroidal illness syndrome is still unclear. This physiologic study evaluated the effect of thyroid hormone treatment on respiratory muscle function in subjects with nonthyroidal illness syndrome and while on mechanical ventilation. The primary end point was neuromechanical efficiency, which provides an estimate of the efficiency of diaphragmatic contraction. Secondary end points were the transdiaphragmatic pressure-time product and the swing of the electrical activity of the diaphragm, which reflect the work of breathing and inspiratory effort, respectively. METHODS: Fifteen subjects on mechanical ventilation for >48 h and with a diagnosis of nonthyroidal illness syndrome who had a failed spontaneous breathing trial, received intravenous triiodothyronine. The hormone was administered as an intravenous bolus of 0.4 g/kg triiodothyronine, followed by continuous perfusion at 0.6 g/kg for 24 h. Neuromechanical efficiency was calculated as the ratio between the drop in airway pressure during an expiratory occlusion and the corresponding electrical activity of the diaphragm peak. Recordings were taken at baseline and after 3, 6, and 24 h. RESULTS: After study completion, free triiodothyronine serum concentrations increased in all the subjects (mean ± SD increase, 0.84 ± 0.34 pg/mL). Neuromechanical efficiency showed no significant changes throughout the study (mean ± SD baseline, 1.40 ± 0.87 cm H 2 O/μV; 3 h, 1.28 ± 0.64 cm H 2 O/μV; 6 h, 1.33 ± 0.87 cm H2O/μV; 24 h, 1.41 ± 0.96 cm H 2 O/μV). Similarly, no variations in transdiaphragmatic pressure-time product per min (mean ± SD baseline, 238.1 ± 124 cm H 2 O × s/min; 3 h, 242.5 ± 140.3 cm H 2 O × s /min; 6 h, 247.5 ± 161.7 cm H 2 O × s/min; 24 h, 281.2 ± 201.2 cm H 2 O × s/min) or swing of electrical activity of the diaphragm (mean ± baseline, 20.9 ± 13.1 μV; 3 h, 17.2 ± 8.3 μV; 6 h, 17.4 ± 11.3 μV; 24 h, 20.3 ± 13.7 μV) were observed during hormone administration. CONCLUSIONS: In the subjects on mechanical ventilation who were admitted to the ICU with non-thyroidal illness syndrome, thyroid hormone replacement treatment did not yield any benefit on respiratory muscle function when assessed by neuromechanical efficiency, which indicated that, in these subjects restoring normal levels of serum thyroid hormones is debatable. (ClinicalTrials.gov registration NCT03157466.)