Dynamics and prognostic value of the hypothalamus–pituitary–adrenal axis responses to pediatric critical illness and association with corticosteroid treatment: a prospective observational study
Bibliographic record
Abstract
PURPOSE: Increased systemic cortisol availability during adult critical illness is determined by reduced binding-proteins and suppressed breakdown rather than elevated ACTH. Dynamics, drivers and prognostic value of hypercortisolism during pediatric critical illness remain scarcely investigated. METHODS: This preplanned secondary analysis of the PEPaNIC-RCT (N = 1440), after excluding 420 children treated with corticosteroids before PICU-admission, documented (a) plasma ACTH, (free)cortisol and cortisol-metabolism at PICU-admission, day-3 and last PICU-day, their prognostic value, and impact of withholding early parenteral nutrition (PN), (b) the association between corticosteroid-treatment and these hormones, and (c) the association between corticosteroid-treatment and outcome. RESULTS: ACTH was normal upon PICU-admission and low thereafter (p ≤ 0.0004). Total and free cortisol were only elevated upon PICU-admission (p ≤ 0.0003) and thereafter became normal despite low binding-proteins (p < 0.0001) and persistently suppressed cortisol-metabolism (p ≤ 0.03). Withholding early-PN did not affect this phenotype. On PICU-day-3, high free cortisol and low ACTH independently predicted worse outcome (p ≤ 0.003). Also, corticosteroid-treatment initiated in PICU, which further suppressed ACTH (p < 0.0001), was independently associated with poor outcomes (earlier live PICU-discharge: p < 0.0001, 90-day mortality: p = 0.02). CONCLUSION: In critically ill children, systemic cortisol availability is elevated only transiently, much lower than in adults, and not driven by elevated ACTH. Further ACTH lowering by corticosteroid-treatment indicates active feedback inhibition at pituitary level. Beyond PICU-admission-day, low ACTH and high cortisol, and corticosteroid-treatment, predicted poor outcome. This suggests that exogenously increasing cortisol availability during acute critical illness in children may be inappropriate. Future studies on corticosteroid-treatment in critically ill children should plan safety analyses, as harm may be possible.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".