Early levothyroxine sodium administration and clinical outcomes in patients with sepsis: a MIMIC-IV database analysis

Sepsis is frequently complicated by non-thyroidal illness syndrome (NTIS). Although thyroid hormones are essential for cardiovascular and respiratory stability, their supplementation in sepsis remains controversial due to conflicting evidence. This study aimed to evaluate the impact of thyroid hormone supplementation on 28 day mortality, mechanical ventilation, vasopressor use, ICU length of stay, and changes in SOFA scores in patients with sepsis. We analyzed 20,231 septic patients from the Medical Information Mart for Intensive Care Database IV (MIMIC-IV) database, comparing those treated with levothyroxine sodium within seven days to a control group using 1:4 propensity score matching. Early levothyroxine sodium administration was significantly associated with increased 28 day mortality in both the original (HR 2.48, 95% CI 1.96-3.15; P < 0.001) and propensity score matching (PSM) cohorts (HR 2.38, 95% CI 1.75-3.23; P < 0.001). The treatment group required higher cumulative norepinephrine equivalents (P = 0.006) and longer vasoactive support duration. Multistate modeling revealed that the treatment group had fewer days alive without mechanical ventilation (17.8 vs. 21.8 days; P < 0.001) and fewer days discharged alive (11.3 vs. 13.4 days; P = 0.006). In patients with less severe sepsis, levothyroxine sodium administration should be approached with particular caution, as it may be associated with adverse clinical outcomes.