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Inflammatory Biomarkers Are Associated With a Decline in Functional Status at Discharge in Children With Acute
Erin F Carlton1,2, Heidi M Weeks3, Mary K Dahmer1
1Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI.
Insights
Higher levels of interleukin-1 receptor antagonist and thrombomodulin in children with acute respiratory failure are linked to worse functional outcomes at discharge. Persistent inflammation may contribute to functional decline in survivors.
Area of Science:
- Pediatric critical care medicine
- Inflammation and immunology
- Biomarker research
Background:
- Acute respiratory failure (ARF) in children can lead to long-term functional morbidity.
- Identifying early predictors of functional outcomes is crucial for improving care.
- Plasma biomarkers may offer insights into the inflammatory processes affecting recovery.
Purpose of the Study:
- To investigate the association between specific plasma biomarkers and functional outcomes in pediatric ARF survivors.
- To determine if early inflammatory markers predict functional morbidity at hospital discharge.
Main Methods:
- Secondary analysis of a clinical trial involving 22 PICUs.
- Included children aged 2 weeks to 17 years requiring mechanical ventilation.
- Assessed functional status using the Pediatric Overall Performance Category (a measure of neurological and functional status).
Main Results:
- Among survivors, 40 out of 427 experienced worsening functional status.
- Interleukin-8 and plasminogen activator inhibitor-1 showed no significant relationship with functional decline.
- Elevated interleukin-1 receptor antagonist and thrombomodulin on days 2 and 3 were associated with worse functional status, particularly thrombomodulin on day 2 after multivariable adjustment.
Conclusions:
- Higher levels of interleukin-1 receptor antagonist and thrombomodulin post-intubation are associated with poorer functional outcomes in pediatric ARF survivors.
- Persistent inflammation, indicated by these biomarkers, may play a role in functional decline.
- These findings highlight potential targets for interventions to mitigate long-term morbidity.
Abstract:
To evaluate the link between early acute respiratory failure and functional morbidity in survivors using the plasma biomarkers interleukin-8, interleukin-1 receptor antagonist, thrombomodulin, and plasminogen activator inhibitor-1. We hypothesized that children with acute respiratory failure with higher levels of inflammation would have worse functional outcomes at discharge, as measured by Pediatric Overall Performance Category.
Design:
Secondary analysis of the Genetic Variation and Biomarkers in Children with Acute Lung Injury (R01HL095410) study.
Setting:
Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622) and the ancillary study (Biomarkers in Children with Acute Lung Injury).
Subjects:
Children 2 weeks to 17 years requiring invasive mechanical ventilation for acute airways and/or parenchymal lung disease. Patients with an admission Pediatric Overall Performance Category greater than 3 (severe disability, coma, or brain death) were excluded.
Interventions:
None.
Measurements And Main Results:
Among survivors, 387 patients had no worsening of Pediatric Overall Performance Category at discharge while 40 had worsening functional status, defined as any increase in Pediatric Overall Performance Category from baseline. There was no significant relationship between worsening of Pediatric Overall Performance Category and interleukin-8 or plasminogen activator inhibitor-1 on any day. There was no significant relationship between interleukin-1 receptor antagonist, or thrombomodulin, and worsening Pediatric Overall Performance Category on day 1. Plasma interleukin-1 receptor antagonist and thrombomodulin were significantly elevated on days 2 and 3 in those with worse functional status at discharge compared with those without. In multivariable analysis, interleukin-1 receptor antagonist and thrombomodulin were associated with a decline in functional status on days 2 and 3 after adjustment for age and highest oxygenation index. However, after adjusting for age and cardiovascular failure, only day 2 thrombomodulin levels were associated with a worsening in Pediatric Overall Performance Category.
Conclusions:
Higher levels of interleukin-1 receptor antagonist or thrombomodulin following intubation were associated with worse Pediatric Overall Performance Category scores at hospital discharge in children who survive acute respiratory failure. These data suggest that persistent inflammation may be related to functional decline.
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