Effect of tight glucose control with insulin on the thyroid axis of critically ill children and its relation with outcome

Abstract

Context: Tight glucose control (TGC) to normal-for-age fasting blood glucose levels reduced morbidity and mortality in surgical adult and pediatric intensive care unit (ICU) patients. In adults, TGC did not affect the illness-induced alterations in thyroid hormones. With better feeding in children than in adult patients, we hypothesized that TGC in pediatric ICU patients reactivates the thyroid axis.

Objective: The aim of this study was to assess the impact of TGC on the thyroid axis in pediatric ICU patients and to investigate how these changes affect the TGC outcome benefit.

Design and patients: We conducted a preplanned analysis of all patients not treated with thyroid hormone, dopamine, or corticosteroids who were included in a randomized controlled trial on TGC (n=700).

Main outcome measures: Serum TSH, T4, T3, and rT3 were measured upon admission and on ICU day 3 or the last ICU day for patients discharged earlier. Changes from baseline were compared for the TGC and usual care groups. The impact on the outcome benefit of TGC was assessed with multivariable Cox proportional hazard analysis, correcting for baseline risk factors.

Results: TGC further lowered the T)/rT3 ratio (P=0.03), whereas TSH (P=0.09) and T4 (P=0.3) were unaltered. With TGC, the likelihood of earlier live discharge from the ICU was 19% higher at any time (hazard ratio, 1.190; 95% confidence interval, 1.010-1.407; P=0.03). This benefit was statistically explained by the further reduction of T3/rT3 with TGC because an increase in T3/rT3 was strongly associated with a lower likelihood for earlier live discharge (hazard ratio per unit increase, 0.863; 95% confidence interval, 0.806-0.927; P<0.0001).

Conclusions: TGC further accentuated the peripheral inactivation of thyroid hormone. This effect, mimicking a fasting response, statistically explained part of the clinical outcome benefit of TGC.

Trial registration: ClinicalTrials.gov NCT00214916.

Fig. 1.

Simplified overview of the thyroid hormone axis. Major changes within the thyroid axis during the acute phase of critical illness (open signs). Changes within the thyroid axis observed with TGC in critically ill infants and children are depicted with the filled signs. (See Results for details.)

Fig. 2.

Effect of TGC on the thyrotropic axis. The line charts (means ± sem) depict the baseline (adm) and day 3 (d3), or last day when patients were discharged earlier (LD), values for serum TSH, T₄, T₃, rT₃, and T₃/rT₃ of patients randomized to TGC (filled ovals) or UC (open ovals). Patients who received dopamine, corticosteroids, or thyroid hormone in the ICU before the day of sampling were excluded for this analysis. P denotes the P value for the difference in the changes from baseline between TGC and UC groups, obtained after correction for baseline risk factors. adm, Admission.