Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Department of Intensive Care Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
Crit Care. 2021 Dec 16;25(1):430. doi: 10.1186/s13054-021-03858-1.
Critical illness is hallmarked by neuroendocrine alterations throughout ICU stay. We investigated whether the neuroendocrine axes recover after ICU discharge and whether any residual abnormalities associate with physical functional impairments assessed 5 years after critical illness.
In this preplanned secondary analysis of the EPaNIC randomized controlled trial, we compared serum concentrations of hormones and binding proteins of the thyroid axis, the somatotropic axis and the adrenal axis in 436 adult patients who participated in the prospective 5-year clinical follow-up and who provided a blood sample with those in 50 demographically matched controls. We investigated independent associations between any long-term hormonal abnormalities and physical functional impairments (handgrip strength, 6-min walk distance, and physical health-related quality-of-life) with use of multivariable linear regression analyses.
At 5-year follow-up, patients and controls had comparable serum concentrations of thyroid-stimulating hormone, thyroxine (T), triiodothyronine (T) and thyroxine-binding globulin, whereas patients had higher reverse T (rT, p = 0.0002) and lower T/rT (p = 0.0012) than controls. Patients had comparable concentrations of growth hormone, insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 (IGFBP1), but higher IGFBP3 (p = 0.030) than controls. Total and free cortisol, cortisol-binding globulin and albumin concentrations were comparable for patients and controls. A lower T/rT was independently associated with lower handgrip strength and shorter 6-min walk distance (p ≤ 0.036), and a higher IGFBP3 was independently associated with higher handgrip strength (p = 0.031).
Five years after ICU admission, most hormones and binding proteins of the thyroid, somatotropic and adrenal axes had recovered. The residual long-term abnormality within the thyroid axis was identified as risk factor for long-term physical impairment, whereas that within the somatotropic axis may be a compensatory protective response. Whether targeting of the residual abnormality in the thyroid axis may improve long-term physical outcome of the patients remains to be investigated. Trial registration ClinicalTrials.gov: NCT00512122, registered on July 31, 2007 ( https://www.clinicaltrials.gov/ct2/show/NCT00512122 ).
危重病的特点是整个 ICU 住院期间都存在神经内分泌改变。我们研究了 ICU 出院后神经内分泌轴是否恢复，以及任何残留的异常是否与 5 年后评估的身体功能障碍有关。
在 EPaNIC 随机对照试验的这项预先计划的二次分析中，我们比较了 436 名参加前瞻性 5 年临床随访的成年患者和 50 名年龄匹配的对照组的甲状腺轴、生长轴和肾上腺轴的激素和结合蛋白的血清浓度。我们使用多变量线性回归分析研究了任何长期激素异常与身体功能障碍（握力、6 分钟步行距离和身体健康相关的生活质量）之间的独立关联。
在 5 年随访时，患者和对照组的促甲状腺激素、甲状腺素 (T)、三碘甲状腺原氨酸 (T) 和甲状腺素结合球蛋白的血清浓度相似，而患者的反 T(rT，p = 0.0002) 和 T/rT(p = 0.0012) 低于对照组。患者的生长激素、胰岛素样生长因子-I(IGF-I) 和 IGF 结合蛋白 1(IGFBP1) 浓度相似，但 IGFBP3 较高 (p = 0.030)。患者和对照组的总皮质醇、皮质醇结合球蛋白和白蛋白浓度相似。较低的 T/rT 与握力较低和 6 分钟步行距离较短独立相关(p≤0.036)，较高的 IGFBP3 与握力较高独立相关(p=0.031)。
ICU 入住 5 年后，甲状腺、生长和肾上腺轴的大多数激素和结合蛋白已恢复。甲状腺轴的残留长期异常被确定为长期身体功能障碍的危险因素，而生长轴的残留异常可能是一种代偿性保护反应。针对甲状腺轴的残留异常是否可以改善患者的长期身体结局仍有待研究。
ClinicalTrials.gov：NCT00512122，于 2007 年 7 月 31 日注册（https://www.clinicaltrials.gov/ct2/show/NCT00512122）。
