IMPORTANCE The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial.OBJECTIVE To determine if the transfusion of fresh red blood cells (stored Յ7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children. DESIGN, SETTING, AND PARTICIPANTSThe Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded.INTERVENTIONS Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group. MAIN OUTCOMES AND MEASURESThe primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death.RESULTS Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34).CONCLUSIONS AND RELEVANCE Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells.

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Croup remains the commonest reason for acute upper airway obstruction in children, yet there are scarce contemporary data of airway management in those requiring intubation. We performed a retrospective analysis of the intensive care management of children intubated for croup in two quaternary paediatric intensive care units: Royal Children's Hospital Melbourne, Australia, and Alberta Children's Hospital, Calgary, Canada. Patients intubated for less than three days were compared with those intubated for greater than three days. Patients less than 10 kg body weight were compared to those greater than 10 kg. Demographic, clinical and microbiological data were recorded. Seventy-seven cases of croup requiring intubation were identified. The median duration of intubation was 60 hours. Parainfluenza was the most common viral aetiology, detected in 30% of cases. Antibiotics were prescribed in 51% of patients. Corticosteroids were prescribed pre-intubation in two-thirds of patients and all post-intubation, with the median dose being prednisolone 3 mg/kg/day. Primary extubation failure occurred in 6.5% of patients. Neither the duration of intubation nor patient size were associated with extubation failure. An air leak test was performed in 69% of patients and poorly predicted extubation success. One non-urgent tracheostomy was performed and there was one death from hypoxic ischaemic encephalopathy. Endotracheal tube leak is poorly recorded and may not predict successful extubation.

Methadone has the potential to assist in the management of pain in children with life-limiting illness, but its use is limited by its complex pharmacokinetic profile and limited research on its use in children. This is a retrospective review of the use of methadone as an analgesic in 16 children with life-limiting illness. Efficacy, dosing and side effect profile were analysed. Fifteen (94%) patients had improvements in their analgesia with minimal observed adverse effects. Patients were either rapidly converted from a prior opioid in one change or received methadone as an adjunct medication. Conversions were calculated using ratios frequently in the range of 10:1 to 20:1 from the oral morphine equivalent total daily dose (MEDD). Adjunct initial dosing was a low dose trial, often beginning with 1 mg at night. Only two patients required a dose adjustment due to side effects attributed to methadone. This was despite the cohort having significant underlying illnesses, extensive concurrent medications, and high methadone dosing where needed. Analysis of dosing and ratios indicates that an individualised approach is required. Based on this and on the infrequency of methadone use in this population, specialist assistance with dosing is recommended. Further research, including prospective and pharmacokinetic studies, is recommended.

Children had a parent present at the bedside approximately 60% of the time. The parents of younger, sicker children may benefit from supportive interventions during PICU admission. Further research is needed to examine both extrinsic and intrinsic factors affecting parental presence at the bedside.

Background and Aim: An essential issue for Kawasaki Disease (KD) is the development of coronary artery disease. We decided to investigate (VEGF) subtype gene expression in KD due to the proangiogenic nature of Vasoactive Endothelial Growth Factor A (VEGF). VEGF-A is a known angiogenic molecule with pro-inflammatory effects, whereas the role of VEGFB has been less defined. Method: KD Microarray and RNA-seq datasets were selected using a comprehensive search strategy of the NCBI GEO Dataset, which resulted in eight studies from whole blood. This included three extensive studies in KD (KD1-KD3). Further, one study dataset from coronary artery tissue, the Coronary Artery Dataset (CAD), was also included to appreciate end-stage KD. Results: In CAD, cases of KD versus controls, VEGF-B was up-regulated (p = 4.932e-02). KD1, KD Acute versus convalescent samples, VEGF-A is up-regulated (p=1.258e-07) and VEGF-B was down-regulated (p=1.42e-28). Similar up regulation of VEGF-A and down regulation of VEGF-B was seen in KD2 (p=1.140e-04; p=1.746e-02) and KD3 (p=1.140e-04; p=1.746e-02), both are KD Versus Controls. VEGF-A up-regulated (p=1.140e-04), VEGF-B down-regulated (p=1.746e-02).KD3, KD versus Control; VEGF-A up-regulated (p=1.140e-04), VEGF-B down regulated (p=1.746e-02). Conclusions: In acute KD VEGF-A up-regulation, with VEGFB being down-regulated, the reverse being true of the convalescent situation. This suggests a temporal inverse relationship between VEGF-A and VEGF-B may have biomarker implications. Moreover, a dual therapeutic strategy, enhancing VEGFB while minimizing VEGFA effects, could be a possible advancement over current KD related-therapies. Further work defining the relationship of VEGF-A to VEGF-B in KD-related angiogenesis is suggested.