Pediatric Critical Care Medicine最新文献

Objective: Continuous neuromuscular blocking agent (NMBA) infusion is common in the PICU. There are no pediatric trials evaluating the effect of train-of-four (TOF) monitoring on NMBA dosing. We therefore aimed to determine the effect of adjunctive TOF monitoring using peripheral nerve stimulation on NMBA dosing compared with clinical assessment alone in PICU patients.

Design: Randomized crossover study (Thai Clinical Trial Registry, TCTR20240328002).

Setting: Fourteen-bed general PICU.

Patients: Age 30 days to 18 years who received continuous cisatracurium infusion and were expected to continue the infusion for the next 48 hours.

Interventions: Patients were randomized to start day-1 intervention with either adjunctive TOF or clinical assessment. Crossover occurred each morning between adjunctive TOF and clinical assessment. On adjunctive TOF day, patients received TOF monitoring, and the results were reported to the clinical team. The clinical team used TOF results together with clinical assessment of the depth of paralysis to adjust cisatracurium dosing on adjunctive TOF day. On the clinical assessment day, patients received TOF monitoring but the results were concealed from the clinical team. The clinical team used only clinical assessment of the depth of paralysis to adjust cisatracurium dosing on the clinical assessment day.

Measurements and main results: Pairwise comparison was made between the consecutive adjunctive TOF day and clinical assessment day in the same patient. Sixteen patients completed the study. There were no significant differences on adjunctive TOF day vs. clinical assessment day for total daily cisatracurium dose (median [interquartile range]: 34.0 mg [20.0, 72.8] vs. 35.4 mg [16.8, 59.0], p = 0.87) and for average cisatracurium dose (mean ± sd: 2.36 ± 1.21 vs. 2.41 ± 1.35 µg/kg/min; mean difference -0.06 [95% CI -0.22 to 0.11] µg/kg/min, p = 0.48).

Conclusions: Adjunctive TOF monitoring did not lead to significant difference in cisatracurium dosing compared with clinical assessment alone.

Objectives: Arterial catheter-associated proximal ischemic injury (ACAPII) is a rare but serious complication in critically ill pediatric patients who require arterial access. In a cohort of critically ill children with multiple organ dysfunction syndrome (MODS), we investigated proteomic differences in children who developed ACAPII with the aim of identifying mechanistic pathways that may contribute to the pathogenesis of this complication. We hypothesized that the plasma proteome at MODS onset would differ between children who later develop ACAPII and those who do not.

Design: Single-center cohort study of pediatric patients with MODS defined by modified Proulx criteria who underwent arterial catheter placement. We obtained plasma samples within 48 hours of MODS onset. Grading of ACAPII was completed by the hospital vascular access team using standardized criteria. Proteomic analysis was performed using Olink proximity extension assay. Gene set enrichment analysis was used to identify mechanistic pathways enriched in ACAPII cases.

Setting: Single-center academic PICU.

Patients: Pediatric patients with MODS and arterial access at Children's Hospital of Philadelphia from January 2020 to December 2022.

Interventions: None.

Measurements and main results: Five of 66 (7.6%) MODS patients with arterial access developed ACAPII. Age, severity of illness, and organ dysfunction profiles did not differ between injured and noninjured patients. Six pathways of immune dysregulation, involving Signal Transducer and Activator of Transcription signaling and cytokine-mediated apoptosis, were enriched in patients with ACAPII ( p < 0.0001). Five pathways associated with endothelial dysfunction were also significantly altered in ACAPII patients ( p < 0.0001). Differential expression analysis identified 18 plasma proteins associated with injury after adjustment for age and severity of illness (false discovery rate p < 0.05), supporting the hypothesis that endothelial injury and immune dysregulation may contribute to ACAPII pathogenesis.

Conclusions: In a small pediatric cohort, we identified pathways of immune dysregulation and endothelial dysfunction associated with ACAPII. Because these factors precede ACAPII, there may be a window for treatment.

Objectives: The parenteral anticoagulant bivalirudin has favorable safety and efficacy outcomes compared with unfractionated heparin (UFH) in pediatric patients requiring extracorporeal membrane oxygenation (ECMO), and is frequently monitored using the activated partial thromboplastin time (aPTT). Our group has demonstrated that the dilute thrombin time (dTT) provides superior reliability compared with the aPTT for bivalirudin monitoring, but there is a concern about access to using dTT and its cost. We report a comparative cost analysis of monitoring ECMO patients anticoagulated with bivalirudin or UFH.

Design: Retrospective analysis of total number of laboratory tests ordered at various time points during ECMO (5, 7, 10, 14, and 21 d) using 2024 institutional list prices for each test.

Setting: Single-center quaternary-care ICUs at Cincinnati Children's Hospital and Medical Center (CCHMC).

Patients: Children younger than 18 years supported on ECMO in our ICUs, anticoagulated with UFH (n = 46) or bivalirudin (n = 30) between January 2018 and August 2023.

Interventions: None.

Measurements and main results: The total number of tests (complete blood count, prothrombin time, aPTT, fibrinogen, and antithrombin 3) ordered were lower in patients receiving bivalirudin compared with UFH across multiple time points of ECMO. In comparison with UFH, use of bivalirudin was associated with fewer total tests ordered and lower costs at both early and late time points. At CCHMC, dTT can be run at equivalent cost to aPTT.

Conclusions: From 2018 to 2023, use of dTT monitoring for bivalirudin, rather than aPTT monitoring for UFH, during ECMO was associated with decreased laboratory testing and costs and is available on an automated or semi-automated platform. Overall, our data support the use of dTT-monitored bivalirudin during ECMO support, which is cost-efficient and may lead to reduction in total laboratory testing and blood volume sampling.

Objectives: To test the feasibility and safety of a randomized controlled trial (RCT) delivering nitric oxide into the sweep gas of extracorporeal membrane oxygenation (ECMO) circuits (sNO) in critically ill children. Second, we explored whether use of sNO may influence clinical outcomes.

Design: Prospective pilot single-center open-label RCT (trial registration number ACTRN12619001518156).

Setting: Single-center, tertiary PICU with enrollment between July 2020 and July 2023.

Patients: Patients from birth to 16 years requiring venoarterial or venovenous ECMO support were enrolled.

Interventions: Randomization to sweep flow with an oxygen/nitrogen mix vs. a mix of oxygen, nitrogen and sNO (20 parts per milliion). Randomization was stratified by type of ECMO support (venoarterial vs. venovenous).

Measurements and main results: Of 60 eligible patients 53 underwent randomization. The median (interquartile range [IQR]) was 1 month (0.1-33.5 mo) and 6.2 months (0.5-120.2 mo) for the intervention and control arms, respectively. Venoarterial and venovenous support were used in 35 of 53 (65%) and 18 of 53 (35%) patients, respectively. In all, 17 of 53 (32%) received pulmonary, 23 of 53 (43%) cardiac and 13 of 53 (25%) extracorporeal cardiopulmonary resuscitation support. Median (IQR) survival free of ECMO and survival free of PICU censored at 30 and 90 days were similar: 18.2 days (0-25.2 d) and 69.1 days (0-85.2 d) vs. 20.8 days (0-26.3 d) and 77.7 days (0-85.9 d) with an effect estimate of -3.2 days (-16.6 to 10.1 d) and -8.8 days (-54.2 to 36.6 d) between the intervention and standard care arm. Blood product use, circuit duration to replacement, free plasma hemoglobin, degree of oxygenator thrombus, and incidence of methemoglobinemia were similar between the two groups. No major adverse events occurred related to the treatment allocation or intervention.

Conclusions: This single-center pilot RCT of sNO vs. standard sweep flow in the ECMO circuit demonstrated that such a trial is safe and feasible. However, given no effect of sNO on clinical outcomes was detected further exploration of dose and route of administration of NO should be undertaken before larger, definitive trials are conducted.

Objectives: Acute hypoxemic respiratory failure is a leading cause of death and disability in critically ill children. Pulmonary capillary barrier dysfunction, in large part, drives severity. We aimed to define how blood and tracheobronchial lavage (TBAL) fluid differentially affect pulmonary capillary barrier function and, as a second exploratory aim, identify protein mediators.

Design: We performed a secondary analysis in April and May of 2024 of blood and TBAL samples from a previously completed observational cohort study of mechanically ventilated children collected from October 2018 to February 2020.

Setting: Single PICU.

Subjects: Stored blood and TBAL samples from 65 children requiring mechanical ventilation collected at 24 and 48-72 hours after intubation.

Interventions: None.

Measurements and main results: We quantified inflammatory proteins in plasma and TBAL using Olink Target 48 Cytokine multiplex. We assessed changes in barrier function of cultured human pulmonary microvascular endothelial cells (HPMECs) using electrical cell-substrate impedance to measure transendothelial electrical resistance. Plasma samples from critically ill children significantly enhanced HPMEC barrier function and contained lower concentrations of proinflammatory cytokines compared with TBAL. Over time, the effects of plasma on barrier integrity diminished, while TBAL samples significantly improved barrier function and had reduced abundance of several proinflammatory cytokines. Notably, TBAL samples from children with severe lung injury augmented HPMEC barriers more than those from children without lung injury, highlighting distinct compartmental and disease-specific influences on HPMEC barriers.

Conclusions: These unexpected findings reveal that blood and lung compartments contain differentially abundant proteins that exert distinct and evolving influences on pulmonary endothelial integrity in critically ill children. These results may inform on the timing and compartment-specific assessment of biomarkers, and eventually, delivery of therapies.

Objectives: To measure PICU strain and test for associations between strain and patient outcomes. We hypothesized that patients transferred from the PICU during high compared with low strain periods would be more likely to experience an unplanned PICU readmission within 48 hours.

Design: Retrospective cohort study.

Setting: Thirty-two PICUs in the Virtual Pediatric Systems, LLC database.

Study population: Patients transferred from the PICU between September 1, 2014, and March 31, 2023.

Interventions: None.

Measurements and main results: We characterized volume-based strain metrics daily including census defined as number of PICU patients and turnover defined as number of PICU admissions, transfers, or discharges. To account for fluctuations in bed availability and staffing, we identified the days with the highest (95th percentile) census and turnover for each quarter and each PICU. We used generalized linear mixed models to test for an association between being transferred from the PICU during days with the highest census and turnover (95th percentile) and experiencing an early, unplanned PICU readmission. After adjusting for patient-level confounders and correlation among PICUs, we identified that patients transferred on days when turnover was in the 95th percentile were more likely to experience an early, unplanned PICU readmission (odds ratio, 1.23; 95% CI, 1.14-1.33) compared with those transferred on days when turnover was less than 95% percentile. Being transferred on a day during which the census was in the 95th percentile was not associated with experiencing an early, unplanned readmission.

Conclusions: This multicenter PICU study demonstrated that turnover is a valuable PICU strain metric that should be used to inform clinical operations and staffing decisions to optimize patient outcomes.

Objective: The study goal was to evaluate the outcomes associated with albumin use in children with sepsis and shock compared with those without shock, using causal inference analysis in a multicenter cohort.

Design, setting, and patients: This was a secondary analysis of electronic health record data collected from 13 U.S. PICUs between 2012 and 2018, consisting of children younger than 18 years who met Phoenix sepsis criteria within the first 24 hours of PICU admission.

Interventions: Covariate-balancing propensity score weighting was applied to adjust for indication bias in the albumin use. Patients receiving at least 0.5 g/kg albumin within 24 hours of PICU admission were assigned to the albumin group; others to the control. Only 24-hour survivors were included to address immortal time bias.

Measurements and main results: Overall, 17,307 children with sepsis survived at least 24 hours. Of these, 1,344 patients (7.8%) who received albumin within the first 24 hours, and 9,678 (55.9%) met the criteria for septic shock. A significant interaction between albumin use and shock status was observed (interaction: -0.353, p = 0.007), with albumin administration in pediatric septic shock patients associated with lower in-hospital mortality: odds ratio equals to 0.698 (95% CI, 0.629-0.774), risk ratio equals to 0.746 (95% CI, 0.625-0.891), and hazard ratio equals to 0.688 (95% CI, 0.558-0.848). In contrast, there was no difference in outcomes between the albumin and control groups in the non-shock group.

Conclusions: Early albumin administration was associated with improved outcomes in children with septic shock, but not in those without shock. These results highlight the importance of considering clinical heterogeneity, such as the presence of shock, in identifying treatment-responsive subgroups and enabling more targeted interventions in pediatric sepsis. Further prospective validation is warranted.