Early Enteral Levothyroxine as Rescue Therapy in Cardiac Surgery Patients With Delayed Neurologic Recovery: A Randomized Trial.

OBJECTIVES To evaluate the efficacy and safety of early enteral levothyroxine as rescue therapy for delayed neurologic and respiratory recovery in adults following on-pump cardiac surgery.

DESIGN AND SETTING A single-center, randomized, double-blind, placebo-controlled trial conducted at Ain Shams University Hospitals (Cairo, Egypt).

PARTICIPANTS Seventy adult patients undergoing cardiac surgery with cardiopulmonary bypass who exhibited delayed recovery, defined as requiring mechanical ventilation for >48 hours or having a Glasgow Coma Scale (GCS) score <15 at 48 hours postoperatively.

INTERVENTIONS Participants were randomized to receive either enteral levothyroxine (25-50 µg/d, titrated by body mass index) or an identical placebo from postoperative day 2 until intensive care unit (ICU) discharge.

MEASUREMENTS AND MAIN RESULTS The primary outcome was the change in GCS score from intervention initiation (48 hours postoperatively) to ICU discharge. Secondary outcomes included cardiac function (ejection fraction), catecholamine requirements, 30-day mortality, hospital length of stay, and thyroid hormone levels. The levothyroxine group (n = 35) showed significantly greater neurologic recovery (adjusted mean difference [aMD] in GCS score, +7.81; 95% confidence interval [CI], 5.24-10.38; p < 0.001) with a 128% faster recovery rate (p < 0.001). Cardiac function improved (attenuated ejection fraction decline; aMD, +12.99%; p < 0.001) with 41% to 63% lower catecholamine needs (p ≤ 0.01). Treatment with levothyroxine was associated with a significantly lower 30-day mortality rate (14.3% v 45.7%; adjusted hazard ratio, 0.24 [95% CI, 0.09-0.65]; p = 0.005). Given the small number of events (n = 21), this finding should be considered exploratory. Hospital stay was longer in the levothyroxine group (13.1 days v 10.3 days, p = 0.005), attributed to survivorship bias. Levothyroxine normalized thyroid hormone levels, and each 1-pg/mL increase in free triiodothyronine correlated with a 2.1-point gain in GCS score (p < 0.001).

CONCLUSIONS Early enteral levothyroxine administration in cardiac surgery patients with delayed postoperative recovery was associated with significantly accelerated neurologic recovery and improved cardiac function. The observed reduction in 30-day mortality is hypothesis generating and requires confirmation in a larger, multicenter trial. These findings support further investigation into the integration of thyroid hormone replacement into perioperative care for this high-risk subgroup.