Objectives: To describe a pediatric case of cytokine release syndrome secondary to chimeric antigen receptor-modified T cells associated with acute respiratory distress syndrome. Design: Case report. Setting: PICU. Patients: A 14-year-old boy with refractory B cell precursor acute lymphoblastic leukemia given chimeric antigen receptor cells developed severe cytokine release syndrome 7 days after the drug product infusion with progressive respiratory failure. He was admitted to PICU with a clinical picture of acute respiratory distress syndrome, requiring mechanical ventilation, and secondary hemophagocytic lymphohistiocytosis. Interventions: Hemoadsorption with cartridge column (Cytosorb) in combination with continuous renal replacement therapy was associated to the anti-cytokine therapy (tocilizumab, a monoclonal antibody targeting interleukin-6 receptor). Measurements and Main Results: Decrease of the inflammatory biomarkers (ferritin, interleukin-6, interleukin-10) in the first 96 hours associated with a progressive improvement of acute respiratory distress syndrome (Pao 2/Fio 2 ratio) 7 day after the start of the multimodal treatment. Conclusions: This case suggests that hemoadsorption with cartridge column in combination with continuous renal replacement therapy and tocilizumab is safe and potentially effective in pediatric patients with severe cytokine release syndrome.

Background Cardiovascular instability is common in critically ill children. There is a scarcity of published high-quality studies to develop meaningful evidence-based hemodynamic monitoring guidelines and hence, with the exception of management of shock, currently there are no published guidelines for hemodynamic monitoring in children. The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Cardiovascular Dynamics section aimed to provide expert consensus recommendations on hemodynamic monitoring in critically ill children. Methods Creation of a panel of experts in cardiovascular hemodynamic assessment and hemodynamic monitoring and review of relevant literature—a literature search was performed, and recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. The AGREE statement was followed to prepare this document. Results Of 100 suggested recommendations across 12 subgroups concerning hemodynamic monitoring in critically ill children, 72 reached “strong agreement,” 20 “weak agreement,” and 2 had “no agreement.” Six statements were considered as redundant after rephrasing of statements following the first round of voting. The agreed 72 recommendations were then coalesced into 36 detailing four key areas of hemodynamic monitoring in the main manuscript. Due to a lack of published evidence to develop evidence-based guidelines, most of the recommendations are based upon expert consensus. Conclusions These expert consensus-based recommendations may be used to guide clinical practice for hemodynamic monitoring in critically ill children, and they may serve as a basis for highlighting gaps in the knowledge base to guide further research in hemodynamic monitoring.

Background: Delirium, bed immobilization, and heavy sedation are among the major contributors of pediatric post-intensive care syndrome. Recently, the Society of Critical Care Medicine has proposed the implementation of daily interventions to minimize the incidence of these morbidities and optimize children functional outcomes and quality of life. Unfortunately, these interventions require important clinical and economical efforts which prevent their use in many pediatric intensive care units (PICU).Aim: First, to evaluate the feasibility and safety of a PICU bundle implementation prioritizing delirium screening and treatment, early mobilization (<72 h from PICU admission) and benzodiazepine-limited sedation in a human resource-limited PICU. Second, to evaluate the incidence of delirium and describe the early mobilization practices and sedative drugs used during the pre- and post-implementation periods. Third, to describe the barriers and adverse events encountered during early mobilization.Methods: This observational study was structured in a pre- (15th November 2019–30th June 2020) and post-implementation period (1st July 2020–31st December 2020). All patients admitted in PICU for more than 72 h during the pre and post-implementation period were included in the study. Patients were excluded if early mobilization was contraindicated. During the pre-implementation period, a rehabilitation program including delirium screening and treatment, early mobilization and benzodiazepine-sparing sedation guidelines was developed and all PICU staff trained. During the post-implementation period, delirium screening with the Connell Assessment of Pediatric Delirium scale was implemented at bedside. Early mobilization was performed using a structured tiered protocol and a new sedation protocol, limiting the use of benzodiazepine, was adopted.Results: Two hundred and twenty-five children were enrolled in the study, 137 in the pre-implementation period and 88 in the post-implementation period. Adherence to delirium screening, benzodiazepine-limited sedation and early mobilization was 90.9, 81.1, and 70.4%, respectively. Incidence of delirium was 23% in the post-implementation period. The median cumulative dose of benzodiazepines corrected for the total number of sedation days (mg/kg/sedation days) was significantly lower in the post-implementation period compared with the pre-implementation period: [0.83 (IQR: 0.53–1.31) vs. 0.74 (IQR: 0.55–1.16), p = 0.0001]. The median cumulative doses of fentanyl, remifentanil, and morphine corrected for the total number of sedation days were lower in the post-implementation period, but these differences were not significant. The median number of mobilizations per patient and the duration of each mobilization significantly increased in the post-implementation period [3.00 (IQR: 2.0–4.0) vs. 7.00 (IQR: 3.0–12.0); p = 0.004 and 4 min (IQR: 3.50–4.50) vs. 5.50 min (IQR: 5.25–6.5); p < 0.0001, respectively]. Barriers to early mobilization were: disease severity and bed rest orders (55%), lack of physicians' order (20%), lack of human resources (20%), and lack of adequate devices for patient mobilization (5%). No adverse events related to early mobilization were reported in both periods. Duration of mechanical ventilation and PICU length of stay was significantly lower in the post-implementation period as well as the occurrence of iatrogenic withdrawal syndrome.Conclusion: This study showed that the implementation of a PICU liberation bundle prioritizing delirium screening and treatment, benzodiazepine-limited sedation and early mobilization was feasible and safe even in a human resource-limited PICU. Further pediatric studies are needed to evaluate the clinical impact of delirium, benzodiazepine-limited sedation and early mobilization protocols on patients' long-term functional outcomes and on hospital finances.

Objective: To determine the clinical effect of continuous hemoperfusion with Cytosorb associated with standard Continuous Renal Replacement Therapy on hemodynamics and on clinically relevant outcome parameters in children with septic shock. Design: Retrospective analysis. Setting: Pediatric intensive care unit. Patients: Eight consecutive children with septic shock who received hemoperfusion with Cytosorb while on Continuous Renal Replacement Therapy. Interventions: Continuous hemoperfusion with Cytosorb (adsorber was changed every 24 h). Measurements and main results: Vasoactive-Inotropic Score was measured before and after the extracorporeal blood purification treatment. Bedside refractory septic shock score was calculated before the onset of the extracorporeal blood purification treatment. Time course of cytokines interleukin-6, interleukin-10, and tumor necrosis factor–alpha was measured at Time 0, then every 12 h until the end of blood purification treatment (72 or 96 h). Pediatric intensive care unit survival in our cohort was 90%. Median bedside refractory septic shock score was 2.1. Patients showed improved Vasoactive-Inotropic Score following blood purification (pre: 40.00 post: 8.89 p = 0.0076). Measurement of cytokines level showed a significant reduction of interleukin-6 plasma levels (7977.27–210.18 pg/mL, p = 0.0077) and interleukin-10 plasma levels (from 687.19 to 36.95 pg/mL, p = 0.0180). In those patients with detectable tumor necrosis factor–alpha plasma level, its reduction was not significant ( p = 0.138). The median removal ratio was 80% for interleukin-6, 90% for interleukin-10, and 29% for tumor necrosis factor–alpha. Conclusion: The use of Cytosorb in combination with Continuous Renal Replacement Therapy as blood purification strategy in pediatric septic shock is associated with a rapid hemodynamic stabilization in the first 48 h of treatment and a significant reduction of interleukin-6 and interleukin-10.