Observational studyIntensive care medicine2020
Dynamics and prognostic value of the hypothalamus-pituitary-adrenal axis responses to pediatric critical illness and association with corticosteroid treatment: a prospective observational study.
Observational study in Intensive care medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Persisting neuroendocrine abnormalities and their association with physical impairment 5 years after critical illness.Critical care (London, England) · 2021Trial
- Effect of withholding early parenteral nutrition in PICU on ketogenesis as potential mediator of its outcome benefit.Critical care (London, England) · 2020Trial
- Brain-Region-Mediated Neuroimmune Modulation in Sepsis: Research Advances and Therapeutic Prospects.Journal of inflammation research · 2026Review
- On how to feed critically ill children in intensive care: A slowly shifting paradigm.Clinical nutrition (Edinburgh, Scotland) · 2025Review
- Evaluating treatment and care outcomes for neuromuscular diseases in a pediatric intermediate care setting.Frontiers in pediatrics · 2025Article
- Pro-opiomelanocortin and ACTH-cortisol dissociation during pediatric cardiac surgery.Endocrine connections · 2024Article
- Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness.Clinical epigenetics · 2024Article
- Serum ACTH and Cortisol Level is Associated with the Acute Gastrointestinal Injury Grade in ICU Patients.International journal of general medicine · 2024Article
- Abnormal DNA methylation within genes of the steroidogenesis pathway two years after paediatric critical illness and association with stunted growth in height further in time.Clinical epigenetics · 2023Article
- Glucocorticoid dysfunction in children with severe malaria.Frontiers in immunology · 2023Article
- PN Administration in Critically Ill Children in Different Phases of the Stress Response.Nutrients · 2022Review
- Analysis of Adrenocorticotropic Hormone and Cortisol Levels in Acute Respiratory Distress Syndrome COVID-19 Patients.Disease markers · 2022Article
- Adrenal function/dysfunction in critically ill patients: a concise narrative review of recent novel insights.Journal of anesthesia · 2021Review
- The personalized hypothalamus-pituitary-adrenal axis and the "ubiquitous" differential stress response to critical illness.Intensive care medicine · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIncreased 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.
methodsThis 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.
resultsACTH 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).
conclusionIn 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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