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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.

Long-term outcomes are fundamental in advising parents about the potential future of their children with congenital heart disease (CHD). No published reports have described the health-related quality of life (HRQL) experienced by children with chromosomal abnormalities who had surgery in early infancy for CHD. A study was undertaken to assess HRQL among children with chromosomal abnormalities and CHD. The authors hypothesized that these children have a worse HRQL than healthy children or a cohort of children matched for CHD diagnosis. Infants with chromosomal abnormalities undergoing cardiac surgery for CHD at 6 weeks of age or younger at the Stollery Children's Hospital between July 2000 and June 2005 were included in the study. The HRQL of these infants was assessed using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales completed by their parents at a 4-year follow-up evaluation. The study compared the scores for 16 children with normative data. The children with chromosomal abnormalities and CHD had significantly lower mean total PedsQL (71.3 vs. 87.3; p < 0.0001), Psychosocial Summary (70.3 vs. 86.1; p < 0.0001), and Physical Summary (74.3 vs. 89.2; p = 0.0006) scores. Compared with the matched children, those with chromosomal abnormalities had a significantly lower median total PedsQL (75.0 vs. 84.6; p = 0.03), Physical Summary (79.5 vs. 96.9; p = 0.007), and School Functioning (68.5 vs. 83.0; p = 0.03) scores. A better understanding of the mechanisms and determinants of HRQL in these children has the potential to yield important implications for clinical practice including clarity for treatment decision making as well as determination of targeted supports and services to meet the needs of these children and their families differentially.

Purpose: To evaluate whether variability in milrinone blood levels (MBL) occurs during administration to critically ill children after surgical repair of congenital heart disease, and the clinical relevance of this variability., Methods: Prospective cohort study conducted in the pediatric intensive care unit of a tertiary care teaching and referral hospital. MBL were measured at three time periods after starting milrinone infusion (9-12, 18-24, 40-48 h) and at the end of the infusion. MBL were categorized as within (100-300 ng/ml) or outside the therapeutic range. Low cardiac output syndrome was defined by elevation of either lactate (>2 mmol/l) or arteriovenous oxygen difference (>30%). Five other clinical outcomes were evaluated. Regression analyses evaluated the relationships between MBL and outcomes., Results: Sixty-three patients were included with a total of 220 MBL. Quantification of MBL was by high-performance liquid chromatography. Overall, 114 (52%) MBL were outside the therapeutic range: 78 (36%) subtherapeutic, and 36 (16%) supratherapeutic. Repeated-measures analysis found a significant association between supratherapeutic MBL and low cardiac output syndrome (p = 0.02), and supratherapeutic MBL were associated with arterial-central venous oxygen saturation difference >30% at time 3 (p = 0.007)., Conclusions: In this cohort, nontherapeutic MBL were common. Further investigation of milrinone dosing recommendations may improve the postoperative outcomes of children.