Effects of Thyroid Hormone Treatment on Diaphragmatic Efficiency in Mechanically Ventilated Subjects With Nonthyroidal Illness Syndrome

Abstract

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/V; 3 h, 1.28 ؎ 0.64 cm H 2 O/V; 6 h, 1.33 ؎ 0.87 cm H2O/V; 24 h, 1.41 ؎ 0.96 cm H 2 O/V). 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 V; 3 h, 17.2 ؎ 8.3 V; 6 h, 17.4 ؎ 11.3 V; 24 h, 20.3 ؎ 13.7 V) were observed during hormone administration. CONCLUSIONS: In the subjects on mechanical ventilation who were admitted to the ICU with nonthyroidal 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.

Can Thyroid Hormone Strengthen the Diaphragm in Nonthyroidal Illness?

“…The authors concluded that thyroid hormone replacement did not benefit critically ill subjects with NTIS. 20 These results do not support further evaluation of the role of thyroid replacement for patients with NTIS and add to other work suggesting that NTIS may be adaptive, rather than pathological.…”

“…17 The contribution of NTIS to respiratory failure and whether thyroid hormone replacement improves respiratory muscle function remains unknown, and thyroid hormone replacement in critically ill patients with NTIS has not been shown to improve outcomes. 18,19 The paper by Bello and colleagues 20 in this issue of the Journal takes nonthyroidal illness, common in the ICU and potentially linked to respiratory muscle function, and uses diaphragmatic neuromuscular efficiency (NME) as a surrogate end point, seeking to show whether a larger clinical trial is worthwhile.…”

“…NME was calculated as the ratio of the peak negative fall in airway opening pressure and the corresponding EA di peak. 20 If thyroid replacement were to have beneficial effects, one would expect treatment to raise NME (ie, more pressure is produced for similar neural stimulus). In addition, NME was used as an index to convert the full EA di signal into P di , allowing the estimation of secondary outcomes including the pressure-time product of the diaphragm per breath (PTP di /breath) and per minute (PTP di /min).…”

“…A strength of the investigation by Bello et al 20 relates to how the study population was selected. Identifying subjects already failing a spontaneous breathing trial seems likely to narrow the population to a subset at risk for prolonged ventilation and for whom diaphragm-targeted therapies could be beneficial.…”

Nonthyroidal Illness Syndrome Across the Ages

“…Furthermore, T3 treatment did not affect mortality in patients suffering from acute burn injury [35]. T3 infusion in mechanically ventilated patients with NTIS also did not affect respiratory muscle function [36]. In acutely ill patients with low serum T4 levels, T4 treatment did not affect mortality [37] or even increased it [38].…”