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Background: Sepsis, a severe inflammatory response to infection, is a global health priority due to its high mortality and long-term disability rates. Its pathophysiology involves both inflammation and immune suppression. Managing sepsis requires significant healthcare resources and expenditure, with sepsis being a leading cause of hospital costs. Gut microbiotas play a crucial role in sepsis, and probiotics show promise in managing it by restoring microbial balance. Despite advances, targeted therapies for sepsis remain elusive, necessitating innovative approaches such as probiotic therapy. Method: Fifty-four eligible patients with sepsis will be randomly assigned to either the synbiotic or placebo group. The synbiotic supplement, KidiLact, comprises ten probiotic strains and prebiotic fructooligosaccharides. Participants will receive two sachets daily for 7 days, mixed with sterile water and administered orally or via gavage. Inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) will be evaluated. Anthropometric measurements, nutritional assessment, biochemical analysis, and clinical evaluation will be conducted to assess treatment outcomes. Statistical analysis will be performed to compare results between the two groups, employing SPSS version 19 with a significance level of P <.05. Conclusion: This randomized clinical trial aims to evaluate synbiotic supplementation effects on inflammatory markers and clinical outcomes in pediatric sepsis patients in the pediatric intensive care unit (PICU). Probiotics have shown promise in reducing proinflammatory cytokines like IL-6, TNF-α, and CRP, which are vital in the inflammatory response. Synbiotics can enhance gut integrity, preventing pathogen translocation and reducing inflammation. If our expectations regarding the effects of probiotics are correct, we can use them as a cost-effective supplement to improve the condition of pediatric sepsis in hospitals. Trial registration: IRCT,IRCT20230523058266N1 Registered 30 October 2023, https://irct.behdasht.gov.ir/trial/71397. [ABSTRACT FROM AUTHOR]

Background : Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration–time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. Methods: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. Discussion: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. Trial registration: Eudract number: 2019–004538-40. Registered on 2020–09-08 ClinicalTrials.gov NCT046666948. Registered on 2020–11-28 [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV+ children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense. In this study of 47 critically ill RSV+ children, we coupled NK cell immunophenotype and cytotoxic function with clinical parameters to identify an NK cell immune signature of severe pediatric RSV disease. Airway NK cells were increased in intubated RSV+ children with severe hypoxemia and prolonged duration of mechanical ventilation and were correlated with clinical severity scores. Peripheral blood NK cells were decreased in RSV+ patients and had altered activating receptor expression, with increased expression of CD69 and decreased expression of NKG2D. Ex vivo, circulating NK cells from RSV+ patients exhibited functional impairment characterized by decreased cytotoxicity as well as aberrant immune synapse assembly and lytic granule trafficking. NK cell frequency and phenotype correlated with clinical measures that defined disease severity. These findings implicate a role for NK cells in mediating RSV immunopathology and suggest that an altered NK cell immunophenotype is associated with severe RSV disease in young children. Editor's summary: Nearly all children are infected with respiratory syncytial virus (RSV) by 2 years of age. Although most children only develop mild symptoms, some can develop severe diseases requiring hospitalization. To better understand the potential drivers of severe disease, Reilly et al. analyzed airway and peripheral blood immune cells from pediatric patients infected with RSV requiring hospitalization. The authors found that natural killer (NK) cells were increased in the airways of children with severe RSV. A corresponding decrease was observed in peripheral blood NK cells. Moreover, the NK cells exhibited an altered phenotype and were less effective at killing target cells ex vivo. These data suggest that these NK cells may be drivers of RSV immunopathology. —Courtney Malo [ABSTRACT FROM AUTHOR]

Background: Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT. Methods: We developed a CKRT "module" in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2–25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m2), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m2 vs high-dose of 8000 mL/h/1.73 m2), and fluid accumulation (0–30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa. Results: Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100–150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function. Conclusions: Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones are essential for normal growth, development, and metabolic regulation. Their levels are often altered in critically ill children, a condition referred to as euthyroid sick syndrome or non-thyroidal illness. These changes are associated with poor outcomes, including organ failure and death, especially in severe cases of sepsis, trauma, and malnutrition. Monitoring thyroid hormone levels in pediatric intensive care settings is critical for managing critically ill children effectively. The objective of this study was to assess thyroid hormone profile in critically ill children admitted to the Pediatric Intensive Care Unit (PICU) at Cheluvamba Hospital and to correlate these hormonal changes with clinical outcomes. Methods: A prospective observational study was conducted over six months in Cheluvamba Hospital, Mysore. The study included 60 children (aged 2 months to 18 years), with 30 critically ill children in the experimental group and 30 relatively healthy children in the control group. Thyroid hormone levels, including T3, T4, TSH, FT3, and FT4, were measured and compared between the two groups. Statistical analyses were performed using the Chi-Square test, with a significance level set at p < 0.05. Results: The study found that 76.7% of the critically ill children had low FT3 levels compared to 20.0% in the control group (p < 0.001). Similarly, 76.7% of the critically ill children had low T3 levels compared to 13.3% in the control group (p = 0.052). No significant differences in FT4 and T4 levels were observed. Mortality was higher in the experimental group (16.7%) compared to the control group (0.0%) (p = 0.02). Conclusion: The study underscores the importance of monitoring thyroid hormone levels, particularly FT3 and T3, in critically ill children. Early therapeutic interventions aimed at correcting thyroid dysfunction may improve clinical outcomes and reduce mortality in pediatric intensive care settings. [ABSTRACT FROM AUTHOR]

The Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee (CTMC) provides evidence-based guidance on safe and effective transfusion practices. Key developments in transfusion medicine in 2023 include findings on red blood cell transfusion strategies for myocardial infarction, updated RBC transfusion guidelines, and the impact of donor sex on transfusion outcomes. Additionally, studies on infectious diseases, blood donor screening, and collections, as well as patient blood management (PBM) metrics and effectiveness, were highlighted. The document also covers advances in hemostasis, hemoglobinopathies, immunohematology, genomics, pediatrics, apheresis, and biotherapies, including the FDA approval of gene therapies for sickle cell disease. Lastly, the text addresses healthcare disparities and diversity, equity, and inclusion (DEI) issues, such as racial disparities in postoperative transfusion outcomes and gender and racial inequity among editorial positions. [Extracted from the article]

Objective: Delirium is an under-recognized problem in critically ill children. Although delirium is common in adults hospitalized with COVID-19, the relationship between pediatric COVID-19 and delirium has not been described. To address this gap, we characterized delirium in critically ill children with different manifestations of COVID-19 and investigated associations among demographic, disease, and treatment factors. We hypothesized that multisystem inflammatory syndrome in children (MIS-C) would be associated with a higher incidence of delirium given its underlying pathophysiology of hyperinflammation. Design: Retrospective, single-center cohort study. Setting: Quaternary-care pediatric intensive care unit (PICU). Patients: Children less than 18 years of age hospitalized in the PICU between March 2020 and March 2023 with either active SARS-CoV-2 infection or serological evidence of prior infection. Measurements and main results: The cohort included 149 PICU hospitalizations among children with evidence of COVID-19. Patients were categorized by reason for PICU admission: 75 (50%) for COVID-19 respiratory disease, 36 (24%) MIS-C, and 38 (26%) any other primary reason with positive COVID-19 testing. Delirium was diagnosed in 43 (29%) patients. Delirium incidence was highest in patients requiring invasive mechanical ventilation (IMV) (56% vs 7.5% in patients who did not require IMV, p <.001). Patients who were exposed to opioids, dexmedetomidine, paralytics or benzodiazepines more frequently experienced delirium compared to those unexposed (p <.001, p <.001, p <.001 and p =.001, respectively). After multivariable adjustment, delirium was associated with IMV (HR 3 [95% CI 1.5–5.7]), female sex (HR 2.4 [1.2–4.7]), and developmental disability (HR 3.4 [95% CI 1–11.1]). There was no association between delirium and reason for PICU hospitalization. Conclusions: Delirium was common among children hospitalized with COVID-19. The overall incidence was much less than has been reported in adults with COVID-19. Delirium reduction efforts should focus on children with developmental disability and minimizing ongoing risks during IMV. [ABSTRACT FROM AUTHOR]

This document discusses the challenges and opportunities of entering a medical toxicology fellowship from a non-traditional residency background. The author, a psychiatry resident, chose to pursue medical toxicology fellowship due to the overlap in patient populations managed by psychiatrists and medical toxicologists. The document provides recommendations for non-traditional applicants, including the importance of developing a network, finding a mentor, and attending toxicology conferences. It also discusses the risks and opportunities of entering the field, such as the potential for innovation and the need to balance clinical interests. The document emphasizes the need for non-traditional applicants to be aware of the effort required to enter the field from outside of emergency medicine. [Extracted from the article]

Background: The ictal–interictal continuum (IIC) consists of several electroencephalogram (EEG) patterns that are common in critically ill adults. Studies focused on the IIC are limited in critically ill children and have focused primarily on associations with electrographic seizures (ESs). We report the incidence of the IIC in the pediatric intensive care unit (PICU). We then compare IIC patterns to rhythmic and periodic patterns (RPP) not meeting IIC criteria looking for associations with acute cerebral abnormalities, ES, and in-hospital mortality. Methods: This was a retrospective review of prospectively collected data for patients admitted to the PICU at Children's National Hospital from July 2021 to January 2023 with continuous EEG. We excluded patients with known epilepsy and cerebral injury prior to presentation. All patients were screened for RPP. The American Clinical Neurophysiology Society standardized Critical Care EEG terminology for the IIC was applied to each RPP. Associations between IIC and RPP not meeting IIC criteria, with clinical and EEG variables, were calculated using odds ratios (ORs). Results: Of 201 patients, 21% (42/201) had RPP and 12% (24/201) met IIC criteria. Among patients with an IIC pattern, the median age was 3.4 years (interquartile range (IQR) 0.6–12 years). Sixty-seven percent (16/24) of patients met a single IIC criterion, whereas the remainder met two criteria. ESs were identified in 83% (20/24) of patients and cerebral injury was identified in 96% (23/24) of patients with IIC patterns. When comparing patients with IIC patterns with those with RPP not qualifying as an IIC pattern, both patterns were associated with acute cerebral abnormalities (IIC OR 26 [95% confidence interval {CI} 3.4–197], p = 0.0016 vs. RPP OR 3.5 [95% CI 1.1–11], p = 0.03), however, only the IIC was associated with ES (OR 121 [95% CI 33–451], p < 0.0001) versus RPP (OR 1.3 [0.4–5], p = 0.7). Conclusions: Rhythmic and periodic patterns and subsequently the IIC are commonly seen in the PICU and carry a high association with cerebral injury. Additionally, the IIC, seen in more than 10% of critically ill children, is associated with ES. The independent impact of RPP and IIC patterns on secondary brain injury and need for treatment of these patterns independent of ES requires further study. [ABSTRACT FROM AUTHOR]

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Objectives: To compare the time taken to reach the target calories and proteins by protocol based "continuous tube feeding (CTF)" and "intermittent tube feeding (ITF)" in critically ill children. Methods: This trial was conducted in the Pediatric Intensive Care Unit (PICU) of a tertiary care institute. Eligible children were randomized to receive CTF or ITF. Target calories were defined as 70% of calorie amount as per the WHO formula and target protein was defined as 1.5 g/kg as per the American Society of Parenteral and Enteral Nutrition (ASPEN) criteria. The primary outcome was time taken to reach target calories, the secondary outcomes were time taken to reach target protein, incidence of feed intolerance, PICU mortality, duration of ventilation, and outcome on 28th day. Results: Fifty-eight children were randomized; 29 in each group. The baseline characters were comparable. The median (IQR) times for reaching target calories were 1.7 (1.4, 2.5) d and 1.8 (1.4, 4.4) d in the CTF and ITF groups, respectively [Hazards ratio (HR) 0.89 (95% CI 0.5, 1.5); p = 0.69]. For the target protein intake, the median times were comparable in the 2 groups [HR 0.82 (95% CI 0.4-1.5); p = 0.55]. The other outcomes were not significantly different between the groups. Conclusions: The authors did not observe any difference in the time taken to reach target calories and protein between the two different modes of delivery of enteral nutrition. [ABSTRACT FROM AUTHOR]

Background: Several studies have shown that vancomycin combined with piperacillin/tazobactam (VPT) increased the risk of acute kidney injury (AKI) compared with other antibiotics in children. However, the epidemiology of VPT-associated AKI in children is unknown. Objective: To evaluate the incidence and risk factors of VPT-associated AKI in children. Data sources: Literature databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and China Biology Medicine Disc were searched from inception to November 2023. References of included studies were also manually checked. Study selection and data extraction: Two independent reviewers selected studies, extracted data, and quality assessment. Meta-analyses were performed to quantify the incidence and risk factors of VPT-associated AKI in children. Data synthesis: Sixteen cohort studies were identified. Overall, the incidence of VPT-associated AKI in children was 24.3% (95% CI: 17.9%-30.6%). The incidence of VPT-associated AKI in critically ill children (26.6%) was higher than that in noncritically ill children (10.9%). Moreover, higher serum vancomycin trough concentration (>15 mg/L), use of vasopressors, combination of nephrotoxins and intensive care unit admission were risk factors for VPT-associated AKI in children (P < 0.05). Relevance to patient care and clinical practice: Identifying high-risk groups and determining safer treatments is critical to reducing the incidence of VPT-associated AKI in children. Conclusions: The incidence of VPT-associated AKI in children is high, especially in critically ill children. Medication regimens should be personalized based on the presence of individual risk factors. Moreover, renal function was regularly assessed throughout treatment with VPT. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic plasma exchange (TPE) is used in a wide spectrum of diseases in critically ill pediatric patients. We aim to review the indications, complications, safety, and outcomes of critically ill children who received TPE. Methods: All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 19 years (January 2013–January 2023) were evaluated retrospectively. A total of 154 patients underwent 486 TPE sessions. Results: Median age was 6 years (2–12.5) and 35 children had a body weight of <10 kg (22.7%). Number of organ failure was 4 (2–6). Liver diseases were the most common indication for TPE (31.2%) followed by sepsis with multiorgan dysfunction syndrome (27.3%). Overall survival rate was 72.7%. The highest mortality was observed in hemophagocytic lymphohistiocytosis group. Non‐survivors had significantly higher number of organ failure (p < 0.001), higher PRISM score (p < 0.001), and higher PELOD score on admission (p < 0.001). Adverse events were observed in 68 (13.9%) sessions. Hypotension (7.8%) and hypocalcemia (5.1%) were the most frequent adverse events. Conclusion: TPE is safe for critically ill pediatric patients with experienced staff. Survival rate may vary depending on the underlying disease. Survival decreases with the increase in the number of failed organs. [ABSTRACT FROM AUTHOR]

Background: The rate of vitamin D deficiency (VDD) in critically ill children worldwide has been estimated at 50%. These children are at risk of multiple organ dysfunction, chronic morbidity, and decreased health related quality of life (HRQL). Pediatric and adult ICU clinical trials suggest that VDD is associated with worse clinical outcomes, although data from supplementation trials are limited and inconclusive. Our group's phase II multicenter dose evaluation pilot study established the efficacy and safety of an enteral weight-based cholecalciferol loading dose to rapidly restore vitamin D levels in critically ill children. Methods: Our aim is to evaluate the impact of this dosing regimen on clinical outcomes. VITdALIZE-KIDS is a pragmatic, phase III, multicenter, double-blind RCT aiming to randomize 766 critically ill children from Canadian PICUs. Participants are randomized using a 1:1 scheme to receive a single dose at enrollment of enteral cholecalciferol (10,000 IU/kg, max 400,000 IU) or placebo. Eligibility criteria include critically ill children aged newborn (> 37 weeks corrected gestational age) to < 18 years who have blood total 25-hydroxyvitamin D < 50 nmol/L. The primary objective is to determine if rapid normalization of vitamin D status improves HRQL at 28 days following enrollment. The secondary objective is to evaluate the impact of rapid normalization of vitamin D status on multiple organ dysfunction. The study includes additional tertiary outcomes including functional status, HRQL and mortality at hospital discharge and 90 days, PICU and hospital length of stay, and adverse events related to vitamin D toxicity. Additionally, we are performing comprehensive vitamin D speciation and non-targeted metabolite profiling as part of a sub-study for the first 100 participants from whom an enrollment and at least one post-intervention blood and urine sample were obtained. Discussion: The VITdALIZE-KIDS trial is the first phase III, multicenter trial to evaluate whether rapid normalization of vitamin D status could represent a simple, inexpensive, and safe means of improving outcomes following pediatric critical illness. Recruitment was initiated in June 2019 and is expected to continue to March 2026. Trial registration: Clinicaltrials.gov, NCT03742505. Study first submitted on November 12, 2018 https://clinicaltrials.gov/study/NCT03742505 [ABSTRACT FROM AUTHOR]

Antimicrobials are frequently used in critically ill children admitted to the Paediatric Intensive Care Unit (PICU). The antimicrobial use data from Indian PICUs is limited using standard metrics such as Days of therapy (DOT). This study aimed to determine the baseline trend of antimicrobial use in PICU of a tertiary care teaching hospital of Raipur district of Chhattisgarh, India using standard metrics with the goal of developing facility-wide antibiotic policy and strengthening the antimicrobial stewardship activities. This active surveillance was conducted over a period of 18 months, from November 1, 2019, to March 21, 2021, in patients aged one month to 14 years who were admitted for ≥ 48 hours to the PICU at a tertiary care teaching hospital of Raipur District. Data on patient characteristics, antimicrobial indications, antimicrobial prescription information, and clinical outcomes were collected using pre-designed data abstraction forms. The descriptive statistic was used to represent the results. The antimicrobial consumption was analyzed according to the WHO AWaRe Class (Access, Watch, and Reserve groups) of antibiotics. The antimicrobial consumption was expressed as DOT/1000 patient-days (PD). A total of 216 patients were surveyed during the study period. The average number of antimicrobials prescribed per hospitalisation was 2.60 (range: 1–12), with 97.22% administered via parenteral route. Overall, DOT/1000-PD was 1318. The consumption of Watch Group antimicrobials was highest with 949 DOT/1000-PD, followed by Access (215) and Reserve Group (154), respectively. Ceftriaxone (208 DOT/1000 PD) was the most commonly prescribed antimicrobial agent, followed by Vancomycin (201), Meropenem (175), Piperacillin-Tazobactam (122) and Colistin (91). The patients who were escalated (28.24%) from empirical antimicrobial therapy had longer median PICU stay (8 days) compared those who were de-escalated (23.6%). Targeted therapy was given in 10.2% patients. The overall mortality rate was 14.35% and was higher (29.3%) in patients in whom empirical therapy was escalated compared to those who were de-escalated or continued. The study established a benchmark for antimicrobials use in the PICU and highlighted priority areas for antimicrobial stewardship intervention to enhance de-escalation rates, enhance targeted therapy, and reduce the overuse of antimicrobials especially belonging to the reserve group. [ABSTRACT FROM AUTHOR]

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children. Severe febrile illnesses in children may be various in presentation and aetiology but involve immune dysfunction amenable to immunomodulation. Here, the authors identify shared neutrophil and T cell dysfunction and a distinct interferon signature in critically ill children with severe febrile illness. [ABSTRACT FROM AUTHOR]

This study aimed to enhance the interpretability and clinical utility of the strength and stressors in parenting (SSF) questionnaire, a parent‐reported questionnaire designed to assess strength, stress and associated risks of mental ill‐health in parents of children with developmental disabilities. Responses to the SSF and a demographic questionnaire were collected from 576 parents of children with (n = 203) and without (n = 373) developmental disabilities. To enhance the interpretability of the SSF, a subset of 129 parents were invited to complete an additional questionnaire consisting of three free‐text questions regarding recent help‐seeking behavior, experiences of mental ill‐health and experiences of parenthood. Parents' responses to the free‐text questions were then categorized as indicative of higher or lower degrees of stress and compared to their SSF score distribution to derive empirical cut‐offs for strength, stress and risk of mental ill‐health as measured by the SSF. The credibility of these cut‐offs was evaluated by comparing the cut‐offs with SSF scores collected from the other 447 parents. Finally, SSF scores from parents of children without developmental disabilities (n = 373) were used to generate percentile values for the SSF to enable a standardized interpretation of SSF scores. To increase the utility of the SSF, we examined a recurring pattern of missing answers to items 23 and 33–38, noted in previous studies of the SSF and repeated in the present study. These items were excluded from further analysis since our examination revealed that they were not missing at random but rather constituted real differences in parental experiences, such as receiving a healthcare allowance, or caring for more than one child. The proposed empirical cut‐offs performed well in discriminating between the two groups and yielded a specificity of 77–89% and a sensitivity of 68–76% for the strength, stress and risk of mental ill‐health subscales of the SSF. This study also presents a conversion chart associating each SSF score with a corresponding percentile value. We propose modifications to the SSF, whereby items 23 and 33–38 are excluded, which will enable a more reliable assessment of parental experiences. This will, together with the empirical cut‐offs and percentile values, enhance the interpretability and clinical utility of the SSF. [ABSTRACT FROM AUTHOR]

Normal respiratory rates (RR) for children under five in the tropics are well-documented, but data for older children are limited. This study tracked RR changes with age and examined associations with nutritional status and environmental factors. We monitored rural Gambian children aged 6 months to 14 years, recording RR during home visits twice weekly over two rainy seasons. Using a generalized additive model, we constructed RR reference curves, and a linear mixed-effect model identified factors influencing RR. A total of 830 children provided 67,512 RR measurements. Their median age was 6.07 years (interquartile range 4.21–8.55) and 400 (48.2%) were female. Age, stunting, ambient temperature, and time of RR measurement were independent predictors of respiratory rate. Strikingly, children showing signs of illness had greater variability in repeat RR measurements. We constructed a RR reference chart for children aged one to 13 years and proposed a cutoff of > 26 breaths/min for raised RR among children aged > 5 years bridging an important gap in this age group. Although the time of data collection, nutritional status, and ambient temperature were predictors of RR, their effect size is not clinically significant enough to warrant a change in the current WHO guidelines owing to the prevailing uncertainty in the measurement of RR. The finding that RRs between repeat measurements were more variable among children with signs of illness suggests that a single RR measurement may be inadequate to reliably assess the status of sick children—a population in which accurate diagnosis is essential to enable targeted interventions with lifesaving treatment. [ABSTRACT FROM AUTHOR]

Background/aim: Thrombomodulin (TM) is found on endothelial cell surfaces and increases in response to endothelial injury of different organs. Interleukin (IL)-8 regulates pulmonary inflammation. TM and IL-8 are candidate biological markers of acute respiratory distress syndrome (ARDS). The aim of the present study was to compare TM and IL-8 levels in pediatric patients with and without ARDS who received respiratory support and to determine their relationships with prognosis. Materials and methods: This was a prospective observational study of 55 patients who received respiratory support in the pediatric intensive care unit. Eighteen patients without active infection were defined as the control group. Two blood samples were taken for serum IL-8 and TM levels on the first and third days of respiratory support. Results: The patient group had significantly higher IL-8 and TM levels than the control group [median IL-8: 102.7 (IQR: 180.42-189.47) vs. 45.4 (55.14-70.49) ng/L, p = 0.011; median TM: 6.9 (6.83-9.18) vs. 3.4 (3.62-5.05) ng/mL, p = 0.021]. Patients with ARDS had significantly higher marker levels on the first and third days than those who did not have ARDS. The TM and IL-8 levels of deceased patients were significantly higher than those of the survivors on the first day. In mortality prediction, the cut-off point for IL-8 was found to be >154.7 ng/L, which had sensitivity of 76.9% and specificity of 73.8%. The cut-off point for TM was >8.4 ng/mL, which had sensitivity of 76.9% and specificity of 66.7%. Conclusion: In our study, higher marker levels correlated with impaired oxygenation and higher mortality. Higher TM and IL-8 levels in ARDS might reflect the degree of vascular injury and inflammation. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to compare the results of ultrasound (US) guidance and the landmark (LM) technique for central venous catheter (CVC) placement in pediatric intensive care units (PICUs) as performed by clinicians. Material and Methods: The patients were divided into two groups according to the technique used: an LM group (459 patients) and a US-guided group (200 patients). We evaluated the success rate, the number of attempts, and the complication rates based on each patient's age and weight. Results: The time required for the successful placement of the CVC was significantly different between the two groups: 10.9±10.8 min in the LM group and 8.1±7.6 min in the US-guided group (p=0.012). Additionally, the average number of attempts for successful catheterization was 1.8±0.8 in the US-guided group; and 2.5 ± 1.4 in the LM group (p=0.024). A total of 115 (17.3%) complications were noted: 24 (3.6%) in the US-guided group and 91 (13.7%) in the LM group (p=0.014). The frequency of complications decreased as the age and weight of the patients increased. When the inserted catheters used by ultrasound were evaluated, 59.5% of them were placed by clinicians who had ultrasound training while 40.5% were inserted by clinicians who did not have ultrasound training. There was no significant difference in the complication rate, number of punctures, and success rates between the ultrasound-trained and untrained clinicians (p=0.476). Conclusion: This is the largest multicenter study comparing the US-guided vs. LM technique for CVC placement in children. We believe that the US-guided CVC procedure is more safe and takes less time than the LM technique. Also, point-of-care ultrasound is useful, beneficial, and easily available for pediatric intensivists. [ABSTRACT FROM AUTHOR]

Background and Objective: Because of the pathophysiological changes associated with critical illness and the use of extracorporeal life support (ECLS) such as continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), the pharmacokinetics of drugs are often altered. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for anakinra in children that accounts for the physiological changes associated with critical illness and ECLS technology to guide appropriate pharmacotherapy. Methods: A PBPK model for anakinra was first developed in healthy individuals prior to extrapolating to critically ill children receiving ECLS. To account for the impact of anakinra clearance by the dialysis circuit, a CRRT compartment was added to the pediatric PBPK model and parameterized using data from a previously published ex-vivo study. Additionally, an ECMO compartment was added to the whole-body structure to create the final anakinra ECLS-PBPK model. The final model structure was validated by comparing predicted concentrations with observed patient data. Due to limited information in guiding anakinra dosing in this population, in-silico dose simulations were conducted to provide baseline recommendations. Results: By accounting for changes in physiology and the addition of ECLS compartments, the final ECLS-PBPK model predicted the observed plasma concentrations in an adolescent receiving subcutaneous anakinra. Furthermore, dosing simulations suggest that anakinra exposure in adolescents receiving ECLS is similar to that in healthy counterparts. Conclusion: The anakinra ECLS-PBPK model developed in this study is the first to predict plasma concentrations in a population receiving simultaneous CRRT and ECMO. Dosing simulations provided may be used to inform anakinra use in critically ill children and guide future clinical trial planning. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effectiveness and safety of using tigecycline as a salvage therapy in critically ill children who did not respond to other antibiotics. Methods We conducted a retrospective cohort analysis that included children who received tigecycline for at least 48 hours and four doses during their pediatric intensive care unit admission. Demographic and clinical features of the subjects were evaluated through a comprehensive review of medical records. The effectiveness of tigecycline was assessed by thoroughly evaluating clinical and microbiological outcomes. Results During the study period, 72 pediatric patients with 88 episodes of infection received tigecycline according to antimicrobial susceptibility in 62.5% of cases and empirically in 37.5%. The median duration of tigecycline therapy was 10 days (range, 2–33 days). Klebsiella pneumoniae (n = 17, 30.9%) was the most frequently isolated pathogen, followed by Acinetobacter baumannii (n = 10, 18.1%). Ventilator-associated pneumonia was the most common infection (n = 29). Of the 55 isolated pathogens, 43 were multidrug-resistant (MDR), and 2 were extensively drug-resistant (XDR) gram-negative bacteria. Clinical response and microbiological clearance were achieved in 42 and 50.9% of episodes, respectively. The overall mortality was 40.9%, with an attributable mortality rate of 29.5%. Conclusion Tigecycline could be used as a salvage therapy for critically ill pediatric patients infected with MDR or XDR pathogens in the lack of alternative treatment options. [ABSTRACT FROM AUTHOR]

Pediatric psychologists are essential staff in the PICU. Their role in caring for critically ill children aligns with clinical practice guidelines for the mental health care needs of this population of patients. This article highlights the role of pediatric psychology in the PICU through illustrative case examples. We discuss lessons learned and future directions for the development and provision of mental health services in PICUs. We address relevant ways for critical care providers to understand the importance of evidence-based psychological care and advocate for the inclusion of psychologists on multidisciplinary PICU teams. As the critical care field continues to focus on an improved understanding of post-intensive care syndrome in pediatrics and the psychological needs of critical care patients, it will be important to consider the vital roles of psychologists and to advocate for improved integration of mental health care in PICUs. [ABSTRACT FROM AUTHOR]

While concerns about high-flow nasal cannula oxygen (HFNC) overuse and associated increased use of hospital resources are rapidly spreading, a two-tiered approach in its use is recommended by recent bronchiolitis guidelines. However, data on its effects in practice have not been reported. We aimed to analyze the trends in use of HFNC, hospitalizations, length of stay (LOS), and intensive care unit (ICU) admissions for bronchiolitis in a tertiary care center using a two-tiered HFNC approach since its introduction in practice. We retrospectively included data of children < 12 months of age who presented to the Paediatric Emergency Department (PED) and were hospitalized for bronchiolitis at our institution in the epidemic season between October 1st and April 30th during the years 2012–2023 and compared the clinical data across the years. Of the 687 hospitalized children included, 79.9% required oxygen supplementation. Use of HFNC significantly increased since its implementation (from 25% in 2012–2013 to over 60% since 2019–2020, p < 0.0001) and was most frequently administered as rescue treatment (in 57.5% of patients). There was no increased trend in ICU admissions (between 1.5% and 10.0% of hospitalizations across seasons, p = 0.40), while LOS, after increasing between 2013 and 2016 (medians between 4.0 and 5.4 days), remained stable thereafter (medians between 3.8 and 4.3 days). Conclusions: The use of HFNC according to a two-tiered approach does not appear to be associated with an increase in ICU utilization or LOS. What is Known: • Bronchiolitis is one of the most common reasons for hospitalization in infants. • Use high-flow nasal canulae oxygen (HFNC) has rapidly spread outside the intensive care unit (ICU) to treat infants with bronchiolitis, although increasing evidence has dampened the initial enthusiasm about their effectiveness. • Concerns nowadays are rising about HFNC overuse and associated increased use of hospital resources, including escalation of care to ICU. What is New: • A more selective use of HFNC according to a "two-tiered approach", intended as a second-line rescue treatment in non-severely ill children who fail standard oxygen therapy, is not associated with increased ICU and length of hospital stay. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with septic shock. Systematic review and meta-analysis of clinical trials including children less than 18 years of age admitted to the pediatric emergency and intensive care unit with severe infection and shock requiring fluid resuscitation. The intervention included balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The primary outcome was mortality rate. Of the 219 citations retrieved, 12 trials (3526 children with severe infection with or without malaria and shock) were included. The pooled results found no significant difference in the mortality rate between groups comparing balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The risk of acute kidney injury (AKI) was significantly less in the BC group compared to the NS group. The certainty of evidence for mortality was of "moderate certainty" in the BC vs NS group, and was of "very low certainty" for the other two groups. Conclusions: The current meta-analysis found no significant difference in the mortality rate between the types of resuscitation fluid, and their speed or volume of administration. However, a significantly decreased risk of AKI was found in the BC group. More evidence is needed regarding the speed and volume of administration of fluid boluses in critically ill children. Prospero registration: CRD42020209066. What is known: • Balanced crystalloids (BC) may be better than normal saline (NS) for fluid resuscitation in critically ill children. What is new: • BC are better than NS for fluid resuscitation in critically ill children as they decrease AKI and hyperchloremia. [ABSTRACT FROM AUTHOR]

Aims: To explore how parents experienced their child with delirium and how parents viewed our delirium management bundle. Design: We conducted a qualitative exploratory descriptive study using semi‐structured individual or dyad interviews. Methods: Twelve semi‐structured interviews with 16 parents of 12 critically ill children diagnosed with delirium in a paediatric intensive care unit were conducted from October 2022 to January 2023 and analysed through a reflexive thematic analysis. Findings: We generated five themes: (1) knowing that something is very wrong, (2) observing manifest changes in the child, (3) experiencing fear of long‐term consequences, (4) adding insight to the bundle, and (5) family engagement. Conclusion: The parents in our study were able to observe subtle and manifest changes in their child with delirium. This caused fear of lasting impact. The parents regarded most of the interventions in the delirium management bundle as relevant but needed individualization in the application. The parents requested more information regarding delirium and a higher level of parent engagement in the care of their child during delirium. Impact: This paper contributes to understanding how parents might experience delirium in their critically ill child, how our delirium management bundle was received by the parents, and their suggestions for improvement. Our study deals with critically ill children with delirium, their parents, and staff working to prevent and manage paediatric delirium (PD) in the paediatric intensive care unit. Reporting Method: The consolidated criteria for reporting qualitative research guidelines were used to ensure the transparency of our reporting. Patient or Public Contribution: No patient or public contribution to the research design. What does this Paper Contribute to the Wider Global Community?: ‐ It increases awareness of the parent's perspective on PD in critically ill children.‐ It shows how PD might affect parents, causing negative emotions such as distress, frustration, and fear of permanent damage.‐ It shows that the parents in our study, in addition to the care bundle, requested more information on delirium and more involvement in the care of their delirious child. [ABSTRACT FROM AUTHOR]

Background: Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU). Objective: We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children. Methods: We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. Results: A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68–80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5–90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. Conclusion: The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol. [ABSTRACT FROM AUTHOR]

Automated pupillometry (AP) facilitates objective pupillary assessment. In this study, we aimed at assessing nursing perspective about the utility of AP in neurocritically ill children to understand acceptance and usage barriers to guide development of a standardized use protocol. We conducted a web-based, cross-sectional, anonymous, Google™ survey of nurses at two independent pediatric ICUs which have been using AP over last four years. The survey included questions related to user-friendliness, barriers, acceptance, frequency of use, and method of documenting AP findings. A total of 31 nurses responded to the survey. A total of 25 nurses (80.6%) used the automated pupillometer and 19 (61.3%) nurses preferred to use the automated pupillometer on critically ill intubated patients. Respondents rated the pupillometer a median [IQR] frequency of use of 7/10 [4–9] and a mean user-friendliness of 8/10 [7–10]. Barriers to pupillometer use included pupillometer unavailability, technical issues, lack of perceived clinical significance, and infection control. Nurses have widely adopted the use of automated pupillometer in the PICU especially for critically ill intubated patients and rate it favorably for user-friendliness. Barriers against its use include limited resources, infection concerns, technical issues, and a lack of perceived clinical significance and training. Implementation of standardized PICU protocol for AP usage in critically ill children, may enhance the acceptance, increase usage and aid in objective assessments. These findings can be used to create a standardized protocol on implementing automated pupillometry in the PICU for critically ill children. • Nurses favor automated pupillometry for critically ill patients. • Nurses rate automated pupillometry high for user-friendliness. • Our survey revealed many key barriers to its pupillometer use. • Implement standardized protocol for effective pupillometer adoption. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Population pharmacokinetics (PK) models may be effective in improving antibiotic exposure with individualized dosing. The aim of the study is to assess cefazolin exposure using a population PK model in critically ill children.We conducted a single‐centre observational study including children under 18 years old who had cefazolin plasma monitoring before and after a cefazolin model implementation. The first concentration at steady state of each cefazolin course was analysed. The optimal exposure was defined by concentration values ranging from free concentration over four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval to total trough or plateau concentration under 100 mg. L−1.A total of 58 patients were included, of whom 39 and 19 children received conventional dosing or model‐informed dosing, respectively. Median [range] age was 2.3 [0.1–17] years old, and median weight was 14.2 [2.9–72] kg. There were more continuous infusions (CI) in the model group than in the conventional group (n = 19/19 [100%] vs. n = 23/39 [59%]). Compared to conventional dosing, model‐informed dosing provided more optimal exposure (n = 17/39 [44%] vs. n = 15/19 [79%], P = .01) and less underexposure (n = 18/39 [46%] vs. n = 2/19 [10%], P = .008), without increasing overexposure (n = 4/39 [10%] vs. n = 2/19 [11%], P = 1). Moreover, the time to C‐reactive protein decrease by 50% was significantly shorter in the model group than the conventional group (3 [0.5–13] vs. 4 [1–34]; P = .045).Use of individualized cefazolin model‐informed dosing improves critically ill children's exposure. Further studies are needed to assess the clinical benefit of cefazolin PK model application. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS. Methods: A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available. Results: Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73). Conclusion: Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is used in critically ill children with cardiac and/or respiratory failure. Use is increasing in children with high‐risk comorbidities. Reasons children do not survive ECMO are poorly described. Aims: Describe characteristics and cause of death, compare mortality in children with high‐risk comorbidities, evaluate mortality trends over a decade. Method: All children <18 years old who received ECMO at this institution from 1 January 2011 to 31 December 2020 were described and categorised by outcome: died on or <48 h post‐ECMO, died ≥48 h post‐ECMO, survived to hospital discharge. Children who did not survive ECMO (DNSE) were categorised to: ECMO withdrawal for irrecoverable original condition, withdrawal for poor prognosis neurological condition, brain death, withdrawal for poor prognosis with multiple complex conditions, and unsupportable. Poison regression was used to analyse survival trends. Results: Four hundred twenty‐eight children received ECMO, 19% DNSE, 14% died ≥48 h post‐ECMO and 67% survived. ECMO was electively withdrawn for irrecoverable original condition (39%), poor prognosis for neurological condition (32%) or multiple complex conditions (18%). One hundred twenty‐two children had ≥1 high‐risk comorbidity. Children with genetic syndromes (58%), risk‐adjusted congenital heart surgery score‐1 ≥4 (53%), primary immunodeficiency (50%) had lower hospital survival. No children with malignancy/bone marrow transplant survived to hospital discharge. Overall hospital survival was 67%, with no significant change during the study period (P‐trend = 0.99). Conclusion: Children who DNSE have therapy electively withdrawn for irrecoverable disease or poor prognosis. Children with high‐risk comorbidities have a reasonable chance of survival. This study informs clinicians ECMO may be a therapeutic option. [ABSTRACT FROM AUTHOR]

Background: Many children with severe traumatic brain injury (TBI) receive magnetic resonance imaging (MRI) during hospitalization. There are insufficient data on how different patterns of injury on early MRI inform outcomes. Methods: Children (3–17 years) admitted in 2010–2021 for severe TBI (Glasgow Coma Scale [GCS] score < 9) were identified using our site's trauma registry. We used multivariable modeling to determine whether the hemorrhagic diffuse axonal injury (DAI) grade and the number of regions with restricted diffusion (subcortical white matter, corpus callosum, deep gray matter, and brainstem) on MRI obtained within 7 days of injury were independently associated with time to follow commands and with Functional Independence Measure for Children (WeeFIM) scores at the time of discharge from inpatient rehabilitation. We controlled for the clinical variables age, preadmission cardiopulmonary resuscitation, pupil reactivity, motor GCS score, and fever (> 38 °C) in the first 12 h. Results: Of 260 patients, 136 (52%) underwent MRI within 7 days of injury at a median of 3 days (interquartile range [IQR] 2–4). Patients with early MRI were a median age of 11 years (IQR 7–14), 8 (6%) patients received cardiopulmonary resuscitation, 19 (14%) patients had bilateral unreactive pupils, the median motor GCS score was 1 (IQR 1–4), and 82 (60%) patients had fever. Grade 3 DAI was present in 46 (34%) patients, and restricted diffusion was noted in the corpus callosum in 75 (55%) patients, deep gray matter in 29 (21%) patients, subcortical white matter in 23 (17%) patients, and the brainstem in 20 (15%) patients. After controlling for clinical variables, an increased number of regions with restricted diffusion, but not hemorrhagic DAI grade, was independently associated with longer time to follow commands (hazard ratio 0.68, 95% confidence interval 0.53–0.89) and worse WeeFIM scores (estimate β − 4.67, 95% confidence interval − 8.33 to − 1.01). Conclusions: Regional restricted diffusion on early MRI is independently associated with short-term outcomes in children with severe TBI. Multicenter cohort studies are needed to validate these findings and elucidate the association of early MRI features with long-term outcomes in children with severe TBI. [ABSTRACT FROM AUTHOR]

Abstract Background Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration–time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. Methods Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. Discussion This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. Trial registration Eudract number: 2019–004538-40. Registered on 2020–09-08 ClinicalTrials.gov NCT046666948. Registered on 2020–11-28

Abstract To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p

The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care. In this post-hoc analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI. We then compared the subphenotypes with regard to a composite outcome of in-hospital death or the initiation of renal replacement therapy (RRT). We included 184 patients presenting SA-AKI within 6 h of the initiation of catecholamines. Three distinct subphenotypes were identified: subphenotype A (99 patients) was characterized by a normal urine output (UO), a low SCr and a low [TIMP-2]*[IGFBP7] level; subphenotype B (74 patients) was characterized by existing chronic kidney disease (CKD), a higher SCr, a low UO, and an intermediate [TIMP-2]*[IGFBP7] level; and subphenotype C was characterized by very low UO, a very high [TIMP-2]*[IGFBP7] level, and an intermediate SCr level. With subphenotype A as the reference, the adjusted hazard ratio (aHR) [95%CI] for the composite outcome was 3.77 [1.92–7.42] (p < 0.001) for subphenotype B and 4.80 [1.67–13.82] (p = 0.004) for subphenotype C. Combining conventional kidney function variables with urine measurements of [TIMP-2]*[IGFBP7] might help to identify distinct SA-AKI subphenotypes with different short-term courses and survival rates. [ABSTRACT FROM AUTHOR]

Objective: Vitamin K (VK) is commonly prescribed for pediatric sepsis-induced coagulopathy without trial-derived evidence to support its use for this indication. The purpose of this study was to characterize national prescribing trends for VK in this population. Patients and Methods: This is a multicenter retrospective cohort study using the Pediatric Health Information System registry including children 0 to 17 years of age hospitalized for sepsis in the pediatric intensive care unit from January 2016 through December 2022. The primary outcome was overall, annual, and center-specific VK prescribing rates. Descriptive data included demographics, length of stay, and rates of VK deficiency, hepatic insufficiency, red blood cell (RBC) transfusion, venous thromboembolism (VTE), and mortality. VK prescribing trends were assessed using Joinpoint regression. Descriptive statistics employed included Wilcoxon rank-sum, student's t, and chi-square tests. Results: Of the 31 221 encounters studied, 4539 (14.6%) were prescribed VK (median center-specific rate: 14.2%; interquartile range [IQR]: 8.8-21%) with a linear annual trend decreasing from 17.3% in 2016 to 13.3% in 2022 (−0.6%/year, r 2 =.661). Those prescribed VK had greater rates of hepatic dysfunction (20.5% vs 3.1%), RBC transfusion (26.5% vs 11.2%), VTE (12.5% vs 4.6%), mortality (17.1% vs 4.4%), and median length of stay (16 [IQR: 8-33] vs 8 [4-15] days) (all P <.001). VK deficiency was diagnosed in 0.2% of encounters. Conclusions: In this multicenter retrospective cohort, VK prescribing was common among critically ill children diagnosed with sepsis. Phased trials are needed to demonstrate clinical efficacy and safety for VK in this population. [ABSTRACT FROM AUTHOR]

To evaluate the muscle thickness and prevalence of muscle atrophy of the biceps brachii/brachialis (BB) and quadriceps femoris (QF) in critically ill children using ultrasound (US). The prospective longitudinal study was conducted in the pediatric intensive care unit (PICU) of a tertiary hospital in southern Brazil with children and adolescents of both sexes, aged 1 month to 12 years, on invasive mechanical ventilation for 24 h. US measurements were taken up to 24 h after admission, 72 h after, and weekly until discharge from the PICU. One hundred one patients were selected, of whom 97 underwent two evaluations, 68 three evaluations, and 26 four ultrasound evaluations. The median age was 6 months, with 63 (62.4%) < 1 year old. The most prevalent clinical diagnosis was respiratory diseases (70.3%). There was a reduction in BB thickness from 1 to 2 weeks (− 0.10 cm, p = 0.009) and in QF from 24 h to 2 weeks (− 0.20 cm, p = 0.013) and 72 h to 2 weeks (− 0.18 cm, p = 0.045). The prevalence of muscle atrophy (decrease > 10% in thickness) was 41.2% in at least one muscle group between 24 and 72 h, 39.7% between 24 h and 1 week, and 59.3% between 24 h and 2 weeks. The US allows the evaluation of BB and QF muscle thickness in critically ill children, and monitoring muscles during PICU hospitalization is important. The prevalence of muscle atrophy was 30.8% in the biceps brachii and 46.2% in the quadriceps femoris at the end of 2 weeks of PICU hospitalization, regardless of age and diagnosis. What is Known: • Ultrasound has emerged as a promising method, being a clinically valuable tool for bedside muscle monitoring in critical patients. • Using the ultrasound to measure the muscle thickness in adults has demonstrated good sensitivity for detecting muscle atrophy. However, this method has only been previously validated in few studies with small sample of pediatric patients. What is New: • Using the ultrasound, we observed that critically ill children experienced a loss of muscle thickness and muscle atrophy, especially during the second week of intubation. • The significant prevalence of muscle atrophy at the end of PICU hospitalization highlights the importance of ultrasound in identifying muscle loss. [ABSTRACT FROM AUTHOR]

Direct visualization of the eye can be difficult or impossible when there is significant facial burns, trauma, or edema. We present 4 nonresponsive, critically ill children whose pupils could not be directly visualized. Ophthalmic ultrasound revealed pupillary reactivity at presentation and throughout their recovery. Determining pupillary reactivity in these nonresponsive patients impacted their initial triage, resuscitation, and medical management. We propose that ophthalmic point‐of‐care ultrasonography can assess the pupillary light reflex in critically ill children whose pupils cannot be directly visualized. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate the characteristics of different Acute Gastrointestinal Injury (AGI) grading trajectories and examine their impact on prognosis in the Pediatric Intensive Care Unit (PICU). Methods This retrospective cohort study was conducted at a large children’s hospital in China. The children admitted to the PICU were included. AGI grade was assessed every other day during the initial nine days following PICU admission. Results A total of 642 children were included, of which 364 children (56.7%) exhibited varying degrees of gastrointestinal dysfunction (AGI grade ≥ 2). Based on the patterns of AGI grading over time, six groups were identified: low-stable group, low-fluctuating group, medium-decreasing group, medium-increasing group, high-decreasing group, high-persistent group. The high-persistent group accounted for approximately 90% of all recorded deaths. Compared to low-stable group, both the medium-increasing and high-persistent groups exhibited positive correlations with length of stay in PICU (PICU LOS) and length of stay (LOS). Compared to low-stable group, the five groups exhibited a negative correlation with the percentage of energy received by enteral nutrition (EN), as well as the protein received by EN. Conclusion This study identified six distinct trajectory groups of AGI grade in critically ill children. The pattern of AGI grade trajectories over time were associated with EN delivery proportions and clinical outcomes.

Abstract Background Benzodiazepines and opioids are commonly administered to severely ill children in the pediatric intensive care unit (PICU) for analgesia and sedation. Long-term opioid medication often results in iatrogenic withdrawal syndrome (IWS) as well as tolerance when the dosage of benzodiazepines and opioids are gradually lowered or entirely stopped. Objectives This review aimed to review and summarize existing knowledge and information on IWS in pediatrics. Conclusion IWS in critically ill children is difficult to diagnose and manage. However, detecting and successfully managing IWS is critical to minimizing potentially negative effects during a patient’s ICU stay and after discharge. Further research is required to ascertain the exact and reliable prevalence of IWS among pediatric patients, as well as the benefits and drawbacks of existing assessment tools and treatments.

Background: Benzodiazepines and opioids are commonly administered to severely ill children in the pediatric intensive care unit (PICU) for analgesia and sedation. Long-term opioid medication often results in iatrogenic withdrawal syndrome (IWS) as well as tolerance when the dosage of benzodiazepines and opioids are gradually lowered or entirely stopped. Objectives: This review aimed to review and summarize existing knowledge and information on IWS in pediatrics. Conclusion: IWS in critically ill children is difficult to diagnose and manage. However, detecting and successfully managing IWS is critical to minimizing potentially negative effects during a patient's ICU stay and after discharge. Further research is required to ascertain the exact and reliable prevalence of IWS among pediatric patients, as well as the benefits and drawbacks of existing assessment tools and treatments. [ABSTRACT FROM AUTHOR]

Background/aim: Early detection and prognosis of sepsis in critically ill children is crucial. The aim of this research was to investigate the prognostic ability of pancreatic stone protein (PSP) in validating sepsis and predicting mortality in a prospective observational study. Materials and methods: In a single-center study, pediatric intensive care unit patients were divided into cohorts of confirmed and suspected sepsis, as well as survivors and nonsurvivors. Patients with positive blood culture growth were considered to have confirmed sepsis, while their negative counterparts were considered to have suspected sepsis. Comparisons were made between complete blood counts, laboratory parameters, mortality indices, and C-reactive protein (CRP), procalcitonin (PCT), and PSP levels. The correlations between PSP and alternative inflammatory markers and mortality indices were then analyzed. The diagnostic and prognostic applicability of PSP for sepsis confirmation and mortality prediction was assessed using receiver operating characteristic curve analysis. Results: PSP levels were significantly elevated in patients with confirmed sepsis and within the nonsurvivor segment. In confirming sepsis and predicting mortality, PSP outperformed CRP and PCT in terms of sensitivity. It had sensitivity of 95% in diagnosing sepsis at a cut-off level of 50 ng/L, with an area under the curve (AUC) of 0.67 (95% CI: 0.52-0.81), and sensitivity of 92% in predicting mortality, with an AUC of 0.71 (95% CI: 0.56-0.83). In addition, PSP showed significant correlations with CRP, PCT, and mortality scores. Conclusion: PSP is emerging as a highly sensitive marker for confirming sepsis and predicting mortality in critically ill pediatric patients. Incorporating the PSP biomarker into routine clinical practice could potentially improve the management of pediatric sepsis. [ABSTRACT FROM AUTHOR]

Introduction: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. Methods: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. Results: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610–0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. Conclusion: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice. [ABSTRACT FROM AUTHOR]

A 4-year-old former 26-week premature male presented to the U.S. Naval Hospital Guam emergency department in respiratory failure secondary to human metapneumovirus requiring urgent intubation. His condition was complicated by a bradycardic arrest requiring 15 minutes of resuscitation before the return of circulation. He was admitted to the adult intensive care unit and was managed via pediatric telecritical care from San Diego. He developed acute respiratory distress syndrome, acute renal failure, hypotension requiring multiple pressors, and fluid overload necessitating bilateral chest tubes and two peritoneal drains. A pediatric critical care air transport team departed San Antonio within 36 hours of activation and transported the patient via C-17 to Hawaii, performing a tail swap to a KC-135. Before takeoff, mechanical delays caused prolonged ground time and lack of temperature control resulted in patient's hyperthermia to reach 104.2°F despite the ice packing. The ambient temperature caused equipment malfunction (suction, handheld blood analyzer, and ventilator), necessitating manual bagging. Despite initial temperature challenges, the team removed 700 mL of peritoneal fluid and substantially reduced the patient's ventilator settings. After 22 hours of care, the team arrived with the patient to a civilian pediatric intensive care unit in CA, USA. Over several weeks, the patient made a full recovery. This pediatric critical care air transport mission highlights the complications intrinsic to air transport. Missions of this severity and length benefit from utilization of pediatric specialists to minimize morbidity and mortality. Highlighting the challenges related to preparation, air frame, and equipment malfunction should help others prepare for future pediatric air transports. [ABSTRACT FROM AUTHOR]

Background: Transfusion of red blood cells (RBC) to rapidly increase hemoglobin levels have been associated with increased risks and worse outcomes in critically ill children. The international TAXI consensus from 2018 (pediatric critical care transfusion and anemia expertise initiative) recommended restrictive RBC transfusion strategies in pediatric patients. Objective: To elucidate physicians perioperative RBC transfusion trigger strategies for pediatric patients in the Nordic countries and to investigate what factors influence the decision to transfuse this group of patients. Methods: An electronic web‐based survey designed by the TransfUsion triggers in Pediatric perioperAtive Care (TUPAC) initiative including six different clinical scenarios was sent to anesthesiologist treating pediatric patients at university hospitals in the Nordic countries on February 1, 2023 and closed May 1, 2023. Results: The study had a response rate of 67.7% (180 responders out of 266 contacted). Median hemoglobin thresholds triggering RBC transfusions were 7.0 [IQR, 7.0–7.3] g/dL in a stable young child (1‐year‐old), 7.0 [IQR, 7.0–7.0] g/dL in the stable older child (5‐year‐old), 8.5 [IQR, 8.0–9.0] g/dL in the older child with cardiac disease, 9.0 [IQR, 8.0–10.0] g/dL the older child with traumatic brain injury, 8.0 [IQR, 7.3–9.0] g/dL in stabilized older child with septic shock and 8.0 [IQR, 7.0–9.0] g/dL in the older child with active but non‐life‐threatening bleeding. Apart from specific hemoglobin level, RBC transfusions were mostly triggered by high lactate level (74.2%), increasing heart rate (68.0%), prolonged capillary refill time (48.3%), and lowered blood pressure (47.8%). No statistical difference was found between the Nordic countries, work experience, or enrollment in a pediatric anesthesia fellowship program regarding RBC transfusion strategies. Conclusions: Anesthesiologists in the Nordic countries report restrictive perioperative RBC transfusion strategies for children that are mostly in agreement with the international TAXI recommendations. However, RBC transfusions strategies were modified to be guided by more liberal trigger levels when pediatric patients presented with severe comorbidity such as severe sepsis, septic shock, and non‐life‐threatening bleeding. [ABSTRACT FROM AUTHOR]