Serum levels of the cold stress hormones FGF21 and GDF-15 after cardiac arrest in infants and children enrolled in single center therapeutic hypothermia clinical trials

单中心治疗性低温临床试验中婴儿和儿童心脏骤停后血清冷应激激素 FGF21 和 GDF-15 的水平

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作者:Jeremy R Herrmann, Ericka L Fink, Anthony Fabio, Alicia K Au, Rachel P Berger, Keri Janesko-Feldman, Robert S B Clark, Patrick M Kochanek, Travis C Jackson

Conclusion

Serum levels of FGF21 and GDF-15 increased after pediatric CA, and FGF21 appears to be augmented by TH.

Methods

Secondary analysis of serum samples from clinical trials. We measured FGF21 and GDF-15 levels in pediatric patients post-CA and compared levels to both pediatric intensive care (PICU) and healthy controls. Post-CA, we compared normothermia (NT) vs TH (33 °C for 72 h) treated cohorts at < 24 h, 24 h, 48 h, 72 h, and examined the change in CSHs over 72 h. We also assessed association between hospital mortality and initial levels.

Objective

Fibroblast Growth Factor 21 (FGF21) and Growth Differentiation Factor-15 (GDF-15) are putative neuroprotective cold stress hormones (CSHs) provoked by cold exposure that may be age-dependent. We sought to characterize serum FGF21 and GDF-15 levels in pediatric cardiac arrest (CA) patients and their association with use of therapeutic hypothermia (TH).

Results

We assessed 144 samples from 68 patients (27 CA [14 TH, 13 NT], 9 PICU and 32 healthy controls). Median initial FGF21 levels were higher post-CA vs. healthy controls (392 vs. 40 pg/mL, respectively, P < 0.001). Median GDF-15 levels were higher post-CA vs. healthy controls (7,089 vs. 396 pg/mL, respectively, P < 0.001). In the CA group, the median change in FGF21 from PICU day 1-3 (after 72 h of temperature control), was higher in TH vs. NT (231 vs. -20 pg/mL, respectively, P < 0.05), with no difference in GDF-15 over time. Serum GDF-15 levels were higher in CA patients that died vs. survived (19,450 vs. 5,337 pg/mL, respectively, P < 0.05), whereas serum FGF21 levels were not associated with mortality.

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