Search Results (88)

Pediatric septic shock remains a major cause of morbidity and mortality in critically ill children and is increasingly recognized as a syndrome of profound immunometabolic dysregulation. This narrative review synthesizes current clinical, translational, and mechanistic evidence on the glutamate–glutamine axis in pediatric septic shock. The review focuses on how glutamine and glutamate metabolism may interact with immune-cell function, mitochondrial substrate handling, redox defense, and intestinal barrier integrity, while distinguishing biological plausibility from validated clinical utility. Current evidence supports the glutamate–glutamine axis as a mechanistically relevant pathway and a source of candidate biomarkers, but pediatric-specific data remain limited and do not yet justify routine biomarker use or glutamine-based intervention in unselected children with septic shock. Future studies should use standardized sampling, reproducible analytical methods, pediatric validation cohorts, and phenotype-guided trial designs before this axis can be translated into clinical decision making. Full article

Background: Pediatric septic shock remains a major cause of morbidity and mortality and requires timely recognition and management across multiple hospital settings. Although intensive care support is critical, outcomes are also influenced by earlier phases of care, including emergency department recognition, first-hour treatment, inpatient monitoring, and timely escalation to the pediatric intensive care unit (PICU). Objective: We aimed to review pediatric septic shock across the full hospital trajectory, from emergency department recognition to PICU management and outcomes, with emphasis on diagnostic challenges, early treatment, escalation of care, and prognostic assessment. Methods: This narrative review was based on a structured literature search of PubMed/MEDLINE, Scopus, and the Cochrane Library, with emphasis on international guidelines, consensus statements, systematic reviews, and clinically relevant pediatric studies addressing recognition, resuscitation, escalation, intensive care management, and outcomes in pediatric septic shock. Results: Pediatric septic shock is best approached as a dynamic continuum rather than a single event. Early recognition is complicated by age-dependent physiology, nonspecific presentation, and delayed hypotension. Timely antimicrobial therapy, individualized fluid resuscitation, early vasoactive support, and repeated reassessment during the first hours are central to management. Ward surveillance and prompt escalation to PICU are critical, as delayed recognition of deterioration may worsen organ dysfunction and resource use. In the PICU, phenotype-informed hemodynamic support, fluid stewardship, respiratory support, and organ support are essential. Outcomes should be evaluated beyond mortality to include organ dysfunction burden, duration of support, length of stay, and longer-term functional recovery. Conclusions: Pediatric septic shock outcomes are shaped by the entire hospital care pathway rather than PICU treatment alone. A trajectory-based, continuum-of-care approach may improve timely diagnosis, escalation, and short- and longer-term outcomes. Full article

Background: Pediatric out-of-hospital cardiac arrest (OHCA) is rare and associated with poor outcomes. Evidence from physician-staffed EMS systems remains limited. This study aimed to describe the incidence, presenting rhythms, EMS response intervals, and outcomes of pediatric OHCA, and to describe incidence, presenting rhythms, EMS response intervals, and prehospital outcomes in a local physician-staffed EMS system. Methods: We conducted a retrospective study of all pediatric (0–17 years) OHCA cases managed by the ASL Lecce physician-staffed EMS (southern Italy) between 2013 and 2025. Data were abstracted from standardized records. Variables included demographics, initial rhythm, EMS response intervals, temporal patterns, and return of spontaneous circulation (ROSC). The primary outcome was ROSC during prehospital care. Results: Twenty-seven cases were identified, corresponding to a cumulative incidence of 22.9 per 100,000 children over the study period (annualized incidence 1.73 per 100,000 children-year). Mean age was 11.9 ± 5.5 years (median 15); 59% were male. Initial rhythms were asystole in 81% and ventricular fibrillation (VF) in 19%; no pulseless ventricular tachycardia (pVT) or pulseless electrical activity (PEA) were recorded. Five patients had shockable rhythms, with seven shocks delivered overall. Mean time intervals were: event-to-call 1.0 ± 0.6 min, call-to-arrival 10.3 ± 4.1 min, event-to-arrival 11.3 ± 4.4 min. Arrests clustered during daytime (63%) and summer (41%). ROSC occurred in three patients (11%), two with VF and one with asystole; all arrests with ROSC were daytime events. In descriptive comparisons, ROSC cases showed a shorter call-to-arrival interval (T1–T2), whereas no consistent pattern was observed across all prehospital time intervals. Conclusions: Pediatric OHCA in this Italian physician-staffed EMS was infrequent, usually presented with asystole, and rarely achieved ROSC. Shockable rhythms were associated with better outcomes. Given the small sample size, findings related to response times should be interpreted with caution. System preparedness should include pediatric-specific training, early defibrillation access, and multicenter registries to improve care and track outcomes. Full article

Background/Objectives: Pediatric shock is a final common pathway of cardiovascular failure across diverse emergencies, yet data from mixed emergency cohorts outside intensive care units remain limited. This study aimed to describe the distribution, etiologic subtypes, and clinical correlates of shock in children presenting within a diagnosis-based emergency cohort. Methods: A retrospective single-centre study was conducted in children aged 0–16 years presenting with selected acute pediatric emergencies, among whom cases with and without shock were compared. Shock was defined using documented diagnoses and compatible hemodynamic features, and multiple etiologic types of shock were analyzed, including hypovolemic, septic, cardiogenic, and anaphylactic shock. Demographic and diagnostic variables—age, length of stay, organ support, age strata, and selected comorbidities—and baseline clinical features were compared between children with and without shock using non-parametric and χ²/Fisher’s exact tests. Results: Within the prespecified diagnosis-based analytic cohort, 36/128 children (28.1%) met the study criteria for shock and occurred across all prespecified acute pediatric emergency groups, with the highest proportional burden in heart failure and meningitis; this proportion should not be interpreted as an emergency-department prevalence estimate. Children with shock were younger, with clustering in infants < 1 year and those aged 5–9 years, and tended to stay longer in hospital. Pre-existing cardiac disease, severe dehydration, and altered mental status/coma were more frequent among children with shock. Septic and cardiogenic shock required the most intensive organ support. Conclusions: In this pediatric emergency cohort, shock emerged as a clinically relevant and etiologically heterogeneous complication across diverse acute presentations, with a distinct age-related vulnerability pattern and consistent associations with readily identifiable bedside clinical features. Simple bedside information—particularly cardiac comorbidity, dehydration, and altered consciousness—may assist the early recognition of children with evolving circulatory failure and support closer monitoring and timely escalation of care. By focusing on a mixed emergency population outside the intensive care unit, this study provides a real-world clinical perspective that may help refine early bedside assessment and improve vigilance for shock in pediatric emergency departments. Full article

Introduction: Endotoxin-mediated septic shock is a life-threatening condition characterized by systemic inflammation and hemodynamic instability. While Polymyxin-B hemoadsorption (Toraymyxin^®) is well-studied in adults, its use in pediatric patients remains less explored and requires modified approaches to minimize invasiveness and complications. Case Presentation: We report a 9-year-old boy (25 kg) with endotoxin-mediated septic shock due to Klebsiella pneumoniae, who developed oliguric acute kidney injury requiring continuous renal replacement therapy (CRRT). On Day 4, worsening conditions prompted the initiation of Toraymyxin^® treatment, directly integrated into the ongoing CRRT circuit. This approach minimized extracorporeal volume expansion, avoided circuit replacement, and was complication-free. The patient improved rapidly, allowing CRRT discontinuation and transfer to the ward within 28 days. Conclusions: This case highlights the feasibility, safety, and potential benefits of integrating the Toraymyxin^® cartridge into an ongoing CRRT circuit in pediatric septic shock, minimizing extracorporeal volume, avoiding additional vascular access, and supporting hemodynamic stabilization. Full article

Background: Continuous monitoring of mortality trends and a thorough understanding of death epidemiology in Pediatric Intensive Care Units (PICUs) are critical for healthcare quality assessment, rational resource allocation, and quality improvement initiatives. This study aimed to analyze a decade-long mortality rate, its temporal trends, and the primary causes of death and to elucidate the independent risk factors for early death within a PICU cohort. Methods: This retrospective cohort study included all PICU admissions at the Children’s Hospital of Chongqing Medical University from 1 January 2014, to 31 December 2023. Data collection covered demographic characteristics, primary diagnoses, comorbidities, requirements for mechanical ventilation or vasoactive drugs, lengths of stay, and patient outcomes. The multivariate logistic regression analysis was used to determine independent risk factors associated with early death. Results: Among 21,910 ICU admissions, the overall mortality rate was 2.3% (n = 512), with a historical range of 0.41% to 5.71%, indicating a gradual decline after 2019. Early mortality (death within 24 h of admission) accounted for 13.9% (71/512) of all deaths. Patients in the early mortality group presented with more severe disease conditions, including shock, sepsis, and postoperative status (p < 0.05). Laboratory findings at admission revealed significantly higher procalcitonin and lactate levels, along with lower albumin levels, in this group than in children who died >24 h after admission (p < 0.05). Multivariate analysis revealed that a need for invasive mechanical ventilation (OR = 3.03; 95% CI: 1.68–5.58; p < 0.001), elevated lactate levels (OR = 1.10; 95% CI: 1.02–1.17; p = 0.009), and postoperative status (OR = 0.29; 95% CI: 0.09–0.73; p = 0.017) were independent risk factors for early mortality. Conclusions: Despite an overall decline in mortality since 2019, early mortality among high-risk patients—such as those requiring invasive mechanical ventilation or those presenting with elevated lactate levels—requires attention. Prompt recognition of these risk profiles and timely intervention are crucial for improving outcomes in children. Full article

A rare but potentially fatal hyperinflammatory disease that develops following SARS-CoV-2 infection is called multisystem inflammatory syndrome in children (MIS-C). Mucocutaneous manifestations are common and frequently overlap with other pediatric inflammatory illnesses, including Kawasaki disease, and may serve as early diagnostic indicators. We describe a 6-year-old girl who was previously healthy but was hospitalized in the pediatric intensive care unit due to a high-grade fever, toxic appearance, and quickly progressing mucocutaneous symptoms, such as bilateral non-purulent conjunctivitis and broad maculopapular rash. Myocardial dysfunction, severe anemia and thrombocytopenia, respiratory failure necessitating mechanical ventilation, and hypotensive shock complicated the clinical course. Laboratory tests showed positive SARS-CoV-2 serology and significantly increased inflammatory markers. Several microbiological tests came up negative. Bacterial sepsis and Kawasaki diseases were not included. A diagnosis of MIS-C was made based on clinical, laboratory, and epidemiological data. In addition to supportive intensive care, the patient received systemic corticosteroids and intravenous immunoglobulin. After two weeks, she was released in a stable condition after gradually improving clinically and biochemically. This instance emphasizes how crucial it is to identify noticeable mucocutaneous manifestations as early warning signs of MIS-C. Immunomodulatory therapy must be started as soon as possible in order to minimize serious consequences and enhance the prognosis of afflicted infants. Full article

Background: Septic cardiomyopathy (SCM) is a dynamic and heterogeneous complication of sepsis, driven by systemic inflammation, autonomic dysregulation, and microcirculatory alterations. Pediatric and adult patients share common pathophysiologic mechanisms, but age-dependent differences in cardiovascular physiology produce distinct hemodynamic responses. Methods: A structured narrative review of clinical and experimental studies published between 2000 and 2025 was conducted via PubMed and major critical care literature. Studies were included if they addressed SCM pathophysiology, hemodynamic monitoring, and therapeutic strategies across age groups, while studies focusing on non-septic cardiac dysfunction were excluded. Results: Adult SCM often presents as hyperdynamic, vasoplegic states, whereas pediatric patients more frequently exhibit hypodynamic profiles, reflecting developmental differences in myocardial reserve and autonomic regulation. Evidence suggests that isolated conventional echocardiographic parameters may underestimate myocardial impairment, whereas advanced modalities, including myocardial strain echocardiography and multimodal hemodynamic monitoring, may serve as complementary tools to detect subtle or evolving myocardial dysfunction. Pediatric evidence remains limited, and therapeutic guidance is largely extrapolated from adult studies. Conclusions: SCM should be approached as a time-dependent, physiology-driven condition, requiring repeated, integrated multimodal cardiovascular assessment to guide individualized management. Age-specific hemodynamic profiles highlight the need for standardized diagnostics, prospective validation of monitoring tools, and phenotype-guided interventions to improve outcomes in both adult and pediatric sepsis. Full article

Deleterious variants in SCN5A lead to a wide clinical spectrum that includes pathologies characterized by life-threatening cardiac events (CEs). In the pediatric population, early identification, management, and risk stratification of these pathologies are the main current challenges. This study analyzed a Spanish pediatric cohort (≤18 years) carrying rare SCN5A variants to explore genotype–phenotype correlations. A retrospective descriptive cohort study, including clinical, demographic, and genetic data of probands and their relatives, was conducted. Out of 100 children studied, 69 had definitively deleterious SCN5A variants (26 females, 38%; median age: 3 years, IQR 1–12). The main diagnoses were isolated Brugada syndrome (BrS) (31; 45%); isolated long QT syndrome type 3 (LQT3) (5; 7%); isolated progressive cardiac conduction disease (PCCD) (1; 2%); isolated familial atrial fibrillation (1; 2%); overlapping phenotypes (7; 10%) including: BrS-PCCD (2; 2.8%); BrS-LQT3 (1; 1.4%); premature ventricular contraction-dilated cardiomyopathy (1; 1.4%); BrS-LQT3-PCCD (1; 1.4%); BrS-PCCD-sick sinus syndrome (SSS) (1; 1.4%) and BrS-PCCD-SSS-familial atrial fibrillation (1; 1.4%). Of them, 13 (19%) patients presented with CEs (cardiogenic syncope, ventricular tachycardia/fibrillation, sudden cardiac arrest/death, and appropriate implantable cardio defibrillator shock). These findings underscore the utility of genetic testing for early diagnosis, risk stratification, and personalized management, enhancing preventive strategies for CE prevention in pediatrics. Full article

Background: The best treatment for children with KD who fail to respond to the first dose of IVIG (refractory KD) is currently unknown. The purpose of this study was to determine treatment practices of pediatric rheumatologists in North America who manage IVIG-refractory KD. Methods: A 34-item web-based survey was sent to 102 randomly selected members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). The anonymous survey addressed the use of primary intensification as well as the treatment of IVIG-refractory KD. Results: The response rate was 82%; 56% (all pediatric rheumatologists) completed the survey. Primary intensification was used for macrophage activation syndrome (MAS), KD shock, and those at high risk for coronary artery aneurysms (CAAs) by 84%, 76% and 52% of responders, respectively, with corticosteroids (CSs) used most frequently. For IVIG-refractory KD without CAA, a second dose of IVIG was used most often (63% alone; 23% plus CS). With non-giant CAAs, only 15% used a second IVIG alone, 40% used IVIG plus CS, and 35% took infliximab, usually with CS/IVIG. With giant CAA, treatments used most frequently were CS, a second IVIG, and infliximab (91%, 69%, and 58%, respectively), usually as combinations of two or more medications. Conclusions: Treatment of IVIG-refractory KD varies significantly among North American pediatric rheumatologists, particularly in the presence of CAAs. Our findings emphasize the need for research to identify the most effective therapy for this KD subgroup. The current use of primary intensification and the presence and size of the CAA will need to be considered as consensus treatment plans are developed. Full article

Background: Pediatric heart failure (PHF) is a heterogeneous syndrome with high morbidity, but existing classification systems inadequately capture its developmental and pathophysiological complexity due to reliance on adult-centric parameters. Using machine learning, we aimed to identify clinically distinct PHF phenotypes with unique outcomes and therapeutic implications. Methods: In this multicenter retrospective study, we analyzed 2903 consecutive PHF patients (≤18 years) from 30 Chinese tertiary centers from 20 provinces (2013–2022). Unsupervised machine learning (k-means clustering with PCA) evaluated 99 clinical, biomarker, and echocardiographic variables to derive phenotypes, which were compared for mortality, hospitalization, and treatment responses. Results: Three phenotypically distinct clusters emerged. Cluster 1 (Chronic Hypertensive and Cardiorenal Profile, 30.1%) predominantly affected older children (78%) with hypertension (54.4%), renal dysfunction (creatinine 45.8 μmol/L), and ventricular tachycardia (53.8%). This cluster showed the lowest in-hospital mortality (2.5%) but frequent 7–14 day hospitalizations (35.8%) and the highest beta-blocker use (54.5%). Cluster 2 (Preterm and CHD-Associated HF, 43.4%) comprised preterm infants (71.4%) with congenital heart disease (72.2%) and preserved LVEF (67%), demonstrating the highest mortality (5.1%) and prolonged stays (>30 days: 10.6%) with predominant diuretic (40.6%) and antibiotic use (54.3%). Cluster 3 (Fulminant Myocarditis Profile, 26.5%) exhibited cardiogenic shock with severely reduced LVEF (33%) and elevated BNP (3234 pg/mL), showing bimodal outcomes (4.8% LOS < 3 days vs. 32.2% LOS 15–30 days) and the highest IVIG utilization (46.5%) with intermediate mortality (3.8%). The majority of between-group differences were statistically significant (p < 0.001). Conclusions: Machine learning identified three PHF phenotypes with distinct in-hospital risk profiles and therapeutic implications, challenging current classification systems. These findings highlight the potential for phenotype-specific management strategies and provide a rationale for future research into arrhythmia prevention in hypertensive profiles and early immunomodulation in fulminant myocarditis, while highlighting the need for specialized care pathways for preterm/CHD patients. Prospective validation is warranted to translate this framework into clinical practice. Full article

Background: Septic shock remains a major cause of mortality in critical care, driven by profound vasoplegia, myocardial depression and refractory circulatory collapse. Conventional therapy occasionally fails to restore adequate perfusion, leading to life-threatening multi-organ failure. Methods: This narrative review examines current evidence on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) as a salvage strategy for refractory septic shock, focusing on the pathophysiological rationale, patient selection, timing of initiation and hemodynamic management. Results: Data from observational studies and registry analyses suggest that V-A ECMO may improve survival in patients with septic cardiomyopathy (SCM), with reported survival rates approaching 40% in selected adult cohorts and over 50% in pediatric populations. Early initiation, phenotype-guided selection and precise hemodynamic titration are critical to optimize outcomes. Conclusions: The role of ECMO in septic shock remains controversial and should be restricted to experienced centers and well-defined phenotypes. Future research must refine selection criteria, standardize support strategies and evaluate long-term functional recovery beyond survival. Full article

Background/Objectives: Multisystem inflammatory syndrome in children (MIS-C), a rare but serious post-acute hyperinflammatory condition that occurs in children 2–6 weeks after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or exposure, varies between countries. Despite its serious nature, most children recover without any sequelae. The most frequently reported long-term sequelae are coronary artery aneurysms. This study aimed to describe the epidemiological profile, clinical characteristics (including cardiac manifestations), treatment, and outcomes of multisystem inflammatory syndrome in children (MIS-C) under 14 years of age with SARS-CoV-2 between February 2020 and November 2021 in Kuwait. Methods: Data on sociodemographic factors, co-morbidities, presenting signs and symptoms, as well as laboratory and echocardiography findings were retrieved from the Pediatric COVID registry (PCR-Q8 registry). Results: Of the one hundred and two patients with a provisional diagnosis of MIS-C, eighty-three patients fulfilled the WHO criteria of MIS-C. Thirty-nine of the MIS-C patients were admitted to the intensive care unit, and only one child died due to cardiogenic shock. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Most (63% (10/16)) of the patients had coronary abnormalities, nine patients (56%) had myocardial dysfunction, and six patients (38%) had dual pathologies. Pericarditis occurred in three patients only, whilst six patients (38%) had dual pathologies. Pericarditis occurred in three patients only. Conclusions: MIS-C appears to affect younger children in Kuwait than in other countries; however, the clinical pattern is consistent with other countries. Further studies of an analytical nature are recommended to identify the risk factors associated with MIS-C and its cardiac sequalae to allow for proactive risk reduction. Full article

Background: A cytokine storm can lead to organ dysfunction and death in critically ill children. Extracorporeal hemoperfusion aims to reduce hyperinflammation by filtering out mid-range cytokines (e.g., IL-6), but pediatric data remain limited. Methods: We conducted a narrative review with PRISMA-guided screening of PubMed, Scopus, and Google Scholar for pediatric reports of HA330/HA380 from January 2020 to June 2025. Due to heterogeneity in populations, circuits, and outcome timing, the results were synthesized descriptively. Three studies met the inclusion criteria: a prospective series of 12 patients with septic shock using HA330, a single case of a pediatric heart transplant with HA380 during cardiopulmonary bypass, and a retrospective comparative cohort study of Pediatric Intensive Care Unit (PICU) oncology patients on continuous renal replacement therapy (CRRT) comparing HA330 (n = 11) versus CytoSorb (n = 10). Results: Three studies involving 23 pediatric patients were analyzed. The median age was 8 years, and 56.5% of patients were male. Most patients underwent hemoadsorption with HA330 via continuous renal replacement therapy (CRRT) or continuous venovenous hemodiafiltration (CVVHDF). Post-treatment reductions were noted in interleukin-6 (IL-6) (mean −69.6%), C-reactive protein (CRP) (−59.0%), and procalcitonin (PCT) (−70.4%). Severity scores (Pediatric Logistic Organ Dysfunction-2 (PELOD-2), Pediatric Risk of Mortality-3 (PRISM-3), and Pediatric Sequential Organ Failure Assessment (pSOFA) improved significantly (p = 0.002). The mean PICU stay was 15.6 days. The survival rate was 87%, and no hemoadsorption-related adverse events were reported. Conclusions: HA330/380 hemoadsorption is a safe and potentially effective treatment for pediatric cytokine storms, reducing inflammation and improving clinical status. However, larger, standardized studies are needed to confirm these findings and guide clinical use. Full article

Introduction. Pediatric polytrauma (PPT) and major trauma in pediatric patients (PMT) present unique challenges compared to adult trauma care due to distinct anatomical and physiological differences. PPT/PMT remains the leading cause of death in children, responsible for over 50% of pediatric deaths and 15% of pediatric hospital admissions due to its long-term effects. This single-institution study focuses on the initial management of PPT/PMT from an orthopedics and traumatology point of view. Material and Methods. In the present study, data of PPT/PMT managed in one single institution, an academic level I pediatric trauma center, in patients <18 years of age, were analyzed over different periods. Over a 10-year period, diaphyseal femur fractures were analyzed as indicators of damage control (DCO) versus definitive treatment. Over a 4-year period (2021–2024), the associated lesions of PPT (head injuries, thoracic and abdominal lesions, spine lesions, major blood vessel lesions, and major musculoskeletal injury) were analyzed. Over a 1-year period (2019), the overall in-hospital mortality and admission rates in the pediatric intensive care unit were analyzed. Results. In the 10-year period, among 298 diaphyseal femur fractures, 46/298 (15%) were classified as PPT in which DCO was performed according to age as follows: in the age-group 15–17 years 23/23 (100%) with temporary external fixation (ExFix); in the age group 12–14 years, 9/14 (64%) with ExFix and 5/14 (26%) and elastic stable intramedullary nails (ESINs); in the age group 5–11 years, 1/5 (20%) with ExFix and 4 with ESIN; in the age group 0–4 years, 2/4 (50%) with ESIN and 2/4 (50%) with a cast. In the 4-year period, PPT/PMTs were associated with 60% head injury, 25% thoracic lesion(s), 18% abdominal lesion(s), 16% spine injury, 5% lesion of a major blood vessel, and 30% major musculoskeletal injuries. In 2019, there were 193 patients admitted to the emergency room as PPT/PMT: 115 were ≤12 years old and 78 were >12 years old. On admission, 46% were admitted to the pediatric intensive care unit, and 65% were admitted to the department of traumatology as inpatients. The in-hospital mortality rate was 7%. Discussion and Conclusions. In our institution, pediatric trauma is assessed using the Pediatric Trauma Score (PTS), and the workup follows the ATLS guidelines with a dedicated trauma team. The role of the orthopedic surgeon during the primary evaluation of PPT/PMT is to contribute to stopping bleeding and hemorrhagic shock. In PPT/PMT, DCO in adolescents is superimposable to adults, whilst in babies and children, DCO is still performed, but it is not a form of temporary external fixation. Full article