Pediatric Critical Care Medicine最新文献

Objectives: To test feasibility of a randomized controlled trial (RCT) with an endpoint of time at goal anticoagulation in children on extracorporeal membrane oxygenation (ECMO) randomized to receive bivalirudin vs. unfractionated heparin.

Design: Open-label pilot RCT (NCT03318393) carried out 2018-2021.

Setting: Single-center quaternary U.S. pediatric hospital.

Patients: Children 0 days to younger than 18 years old supported with ECMO in the PICU or cardiovascular ICU.

Interventions: Randomization to bivalirudin vs. unfractionated heparin while on ECMO.

Measurements and main results: Sixteen patients were randomized to bivalirudin, and 14 patients were randomized to heparin. There was no difference in the primary outcome, time spent at goal anticoagulation, for patients randomized to bivalirudin compared with those randomized to heparin. While hemorrhagic complications were similar between study groups, thrombotic complications were higher with six of 16 patients in the bivalirudin group having one or more circuit changes compared with 0 of 14 patients in heparin group (mean difference, 37.5% [95% CI, 8.7-61.4%]; p = 0.02). Patients in the bivalirudin group received less packed RBC transfusions vs. those receiving heparin (median [interquartile range], 6.3 mL/kg/d [2.5-8.4 mL/kg/d] vs. 12.2 mL/kg/d [5.5-14.5 mL/kg/d]; p = 0.02).

Conclusions: In this single-center pilot RCT carried out 2018-2021, we found that the test of anticoagulation therapy of bivalirudin vs. heparin during ECMO was feasible. Larger multicenter studies are required to further assess the safety and efficacy of bivalirudin for pediatric ECMO.

Objectives: We aimed to implement a post-cardiac arrest targeted temperature management (TTM) bundle to reduce the percent of time with a fever from 7% to 3.5%.

Design: A prospective, quality improvement (QI) initiative utilizing the Method for Improvement. The pre-intervention historical control period was February 2019 to March 2021, and the intervention test period was April 2021 to June 2022.

Setting: The PICU of a freestanding, tertiary children's hospital, in the United States.

Patients: Pediatric patients 2 days old or older to 18 young or younger than years old who experienced cardiac arrest, received greater than or equal to 2 minutes of chest compressions, required invasive mechanical ventilation post-resuscitation, and had no documented limitations of care.

Interventions: We developed and implemented a TTM bundle that included standard temperature goals, instructions and training on cooling blanket use, scheduled prescription of antipyretics, an algorithm for managing shivering, and standardized orders in our electronic health record.

Measurements and results: We reviewed data from 29 patients in the pre-intervention period and studied 46 in the intervention period. In comparison with historical controls, the reduction in median (interquartile range [IQR]) percentage of febrile (> 38°C) time per patient associated with the TTM bundle was 0% (IQR, 0-3%) vs. 7% (IQR, 0-13%; p < 0.001). The intervention period, vs. pre-intervention, was associated with fewer patients with fever at any time (16/46 vs. 21/29; mean reduction, 37%; 95% CI, 13.8-54.8%; p = 0.002). We failed to identify an association between the intervention period, vs. pre-intervention, and the development of hypothermia (< 35°C; 8/46 vs. 3/29; mean change, 7%; 95% CI, -10.9% to 21.8%; p = 0.40).

Conclusions: In this QI project, we have demonstrated that implementation of a TTM bundle is associated with reduced duration and frequency of fever in patients who survive cardiac arrest.

Objectives: Extubation failure (EF) in PICU patients is reintubation within 48, 72, or 96 hours of planned extubation (EF48, EF72, and EF96, respectively). Standardized sedation protocols, extubation readiness testing, and noninvasive respiratory support are used to improve efficient liberation from mechanical ventilation (MV). We therefore aimed to review EF rates, time to failure, and the use of noninvasive respiratory support after extubation, 2017-2021.

Design: Retrospective analysis of patients admitted to PICUs contributing to the Virtual Pediatric Systems (VPS, LLC) database, 2017-2021.

Setting: One hundred thirty-six participating PICUs.

Patients: All patients admitted to participating PICUs between January 1, 2017, and December 31, 2021, who had MV and met inclusion criteria for planned extubation.

Interventions: None.

Measurements and main results: There were 111,229 planned extubations with 5,143 reintubations within 48 hours. The EF48, EF72, and EF96 rates were 4.6%, 5.3%, and 5.8%, respectively. Higher rates of EF were associated with age younger than 6 months, underlying genetic conditions, medical comorbidities, or cardiac surgery. Failed extubation was also associated with higher Pediatric Risk of Mortality III scores, longer duration of MV, and longer PICU and hospital lengths of stay. From 2017 to 2021, there was an increase in the use of high-flow nasal cannula oxygen therapy after extubation from 16.6% to 20.2%.

Conclusions: In the VPS 2017-2021 dataset, we have found that the overall EF rates (EF48-EF96) have improved over this 5-year period. We are not able to assess the clinical benefit of this change, but it is evident that over the same period, there has been a concomitant increase in the use of postextubation noninvasive respiratory support. Further work is needed to look at the interaction of these effects in contemporary PICU practice.

Objectives: In post hoc analyses of our previous phase 2b Bayesian randomized clinical trial (RCT), prophylaxis with enoxaparin reduced central venous catheter (CVC)-associated deep venous thrombosis (CADVT) in critically ill older children but not in infants. The goal of the Catheter-Related Early Thromboprophylaxis with Enoxaparin (CRETE) Studies is to investigate this newly identified age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against CADVT in critically ill children.

Design: Two parallel, multicenter Bayesian superiority explanatory RCTs, that is, phase 3 for older children and phase 2b for infants, and an exploratory mechanistic nested case-control study (Trial Registration ClinicalTrials.gov NCT04924322, June 7, 2021).

Setting: At least 15 PICUs across the United States.

Patients: Older children 1-17 years old ( n = 90) and infants older than 36 weeks corrected gestational age younger than 1 year old ( n = 168) admitted to the PICU with an untunneled CVC inserted in the prior 24 hours. Subjects with or at high risk of clinically relevant bleeding will be excluded.

Interventions: Prophylactic dose of enoxaparin starting at 0.5 mg/kg then adjusted to anti-Xa range of 0.2-0.5 international units (IU)/mL for older children and therapeutic dose of enoxaparin starting at 1.5 mg/kg then adjusted to anti-Xa range of greater than 0.5-1.0 IU/mL or 0.2-0.5 IU/mL for infants while CVC is in situ.

Measurements and main results: Randomization is 2:1 to enoxaparin or usual care (no enoxaparin) for older children and 1:1:1 to either of 2 anti-Xa ranges of enoxaparin or usual care for infants. Ultrasonography will be performed after removal of CVC to assess for CADVT. Subjects will be monitored for bleeding. Platelet poor plasma will be analyzed for markers of thrombin generation. Samples from subjects with CADVT will be counter-matched 1:1 to subjects without CADVT from the opposite trial arm. Institutional Review Board approved the "CRETE Studies" on July 1, 2021. Enrollment is ongoing with planned completion in July 2025 for older children and July 2026 for infants.

Objectives: To determine the reliability of the Bleeding Assessment Scale in critically Ill Children (BASIC) definition of bleeding severity in a diverse cohort of critically ill children.

Design: Prospective cohort study.

Setting: Eight mixed PICUs in the Netherlands, Israel, and the United States.

Subjects: Children ages 0-18 years admitted to participating PICUs from January 1, 2020, to December 31, 2022, with bleeding noted by bedside nurse.

Interventions: None.

Measurements and main results: The bleeding events were classified as minimal, moderate, or severe, according to the BASIC definition, by two independent physicians at two different time points. Patient demographic data, laboratory values, and clinical outcomes were collected. Three hundred twenty-eight patients were enrolled. The overall inter-rater reliability was substantial (weighted kappa coefficient, 0.736; 95% CI, 0.683-0.789), and the intra-rater reliability was "almost-perfect" (weighted kappa coefficient, 0.816; 95% CI, 0.769-0.863). The platelet count (p = 0.008), prothrombin time (p = 0.004), activated partial thromboplastin time (p = 0.025), and fibrinogen levels (p = 0.035) were associated with the bleeding severity, but the international normalized ratio was not (p = 0.195). Patients were transfused blood components in response to any bleeding in 31% of cases and received hemostatic medications in 9% of cases. More severe bleeding was associated with increased 28-day mortality, longer hospital length of stay, and more days receiving inotropic support.

Conclusions: The BASIC definition is a reliable tool for identifying and classifying bleeding in critically ill children. Implementing this definition into clinical and research practice may provide a consistent and reliable evaluation of bleeding.

Objectives: Pediatric patients with advanced heart disease (AHD) often receive high intensity medical care at the end of life (EOL). In this study, we aimed to determine whether receipt and timing of pediatric palliative care (PPC) consultation was associated with EOL care intensity of pediatric patients with AHD.

Design: Retrospective cohort study.

Setting: Single-center, 16-bed cardiac ICU (CICU) in a children's hospital in the Mountain West.

Patients: Pediatric patients (0-21 yr) with AHD treated in the CICU and subsequently died from January 2014 to December 2022.

Interventions: None.

Measurements and main results: We compared demographics, EOL characteristics and care, including medical interventions and mortality characteristics for patients by receipt and timing of PPC (i.e., ≥ 30 d from [early] or < 30 d of death [late]) using chi-square and Wilcoxon rank-sum tests. Of 218 patients, 78 (36%) did not receive PPC, 76 received early PPC (35%), and 64 received late PPC (29%). Compared with patients who did not receive PPC, patients receiving PPC had lower EOL care intensity (77% vs. 96%; p = 0.004) and fewer invasive interventions within 14 days of death (74% vs. 92%; p = 0.004). Receipt of PPC, vs. not, was associated with lower rate of death during cardiopulmonary resuscitation (12% vs. 32%; p = 0.004) and more use of comfort care (23% vs. 3%; p = 0.004). Among patients receiving PPC, early PPC was associated with fewer invasive interventions within 14 days of death (65% vs. 85%; p = 0.033). Care intensity was high for patients with early and late PPC.

Conclusions: Early PPC was associated with fewer invasive interventions within 14 days of death, yet the care intensity at EOL remained high. With early PPC, families likely receive timely psychosocial and advance care planning support without significantly altering goals of care.

Objectives: We previously derived the updated Pediatric Sepsis Biomarker Risk for Acute Kidney Injury (PERSEVERE-II AKI) prediction model, which had robust diagnostic test characteristics for severe AKI on day 3 (D3 severe AKI) of septic shock. We now sought to validate this model in an independent cohort of children to the one in which the model was developed.

Design: A secondary analysis of a multicenter, prospective, observational study carried out from January 2019 to December 2022.

Setting: Ten PICUs in the United States.

Patients: Children with septic shock 1 week to 18 years old admitted to the PICU.

Interventions: None.

Measurements and main results: Seventy-nine of 363 patients (22%) had D3 severe AKI, defined as Kidney Disease Improving Global Outcomes stage 2 or higher. Patients were assigned a probability of D3 severe AKI using the PERSEVERE-II AKI model. The model predicted D3 severe AKI with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.85-0.93), sensitivity of 77% (95% CI, 66-86%), specificity of 88% (95% CI, 84-92%), positive predictive value of 65% (95% CI, 54-74%), and negative predictive value of 93% (95% CI, 89-96%). These data represent an increase in post-test probability of D3 severe AKI with a positive test from 22% to 65%, and a prevalence threshold of 28%. On multivariable regression, the PERSEVERE-II AKI prediction model demonstrated greater adjusted odds ratio (aOR) for D3 severe AKI (aOR, 11.2; 95% CI, 4.9-25.3) and lesser aOR for failure of D3 renal recovery from early AKI (aOR, 0.31; 95% CI, 0.13-0.69).

Conclusions: The PERSEVERE-II AKI model demonstrates consistently robust performance for prediction of new or persistent D3 severe AKI in children with septic shock. A major limitation is that actual D3 severe AKI prevalence is below the prevalence threshold for the test, and thus future work should focus on evaluating use in enriched populations.

Objectives: Mortality from pneumonia is three times higher in Asia compared with industrialized countries. We aimed to determine the epidemiology, microbiology, and outcome of severe pneumonia in PICUs across the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN).

Design: Prospective multicenter observational study from June 2020 to September 2022.

Setting: Fifteen PICUs in PACCMAN.

Patients: All children younger than 18 years old diagnosed with pneumonia and admitted to the PICU.

Interventions: None.

Measurements and main results: Clinical, microbiologic, and outcome data were recorded. The primary outcome was PICU mortality. Univariate and multivariable logistic regression was performed to investigate associations between PICU mortality and explanatory risk factors on presentation to the PICU. Among patients screened, 846 of 11,778 PICU patients (7.2%) with a median age of 1.2 years (interquartile range, 0.4-3.7 yr) had pneumonia. Respiratory syncytial virus was detected in 111 of 846 cases (13.1%). The most common bacteria were Staphylococcus species (71/846 [8.4%]) followed by Pseudomonas species (60/846 [7.1%]). Second-generation cephalosporins (322/846 [38.1%]) were the most common broad-spectrum antibiotics prescribed, followed by carbapenems (174/846 [20.6%]). Invasive mechanical ventilation and noninvasive respiratory support was provided in 438 of 846 (51.8%) and 500 of 846 (59.1%) patients, respectively. PICU mortality was 65 of 846 (7.7%). In the multivariable logistic regression model, age (adjusted odds ratio [aOR], 1.08; 95% CI, 1.00-1.16), Pediatric Index of Mortality 3 score (aOR, 1.03; 95% CI, 1.02-1.05), and drowsiness (aOR, 2.73; 95% CI, 1.24-6.00) were associated with greater odds of mortality.

Conclusions: In the PACCMAN contributing PICUs, pneumonia is a frequent cause for admission (7%) and is associated with a greater odds of mortality.

The aim of this "Technical Note" is to inform the pediatric critical care data research community about the "2024 Pediatric Sepsis Data Challenge." This competition aims to facilitate the development of open-source algorithms to predict in-hospital mortality in Ugandan children with sepsis. The challenge is to first develop an algorithm using a synthetic training dataset, which will then be scored according to standard diagnostic testing criteria, and then be evaluated against a nonsynthetic test dataset. The datasets originate from admissions to six hospitals in Uganda (2017-2020) and include 3837 children, 6 to 60 months old, who were confirmed or suspected to have a diagnosis of sepsis. The synthetic dataset was created from a random subset of the original data. The test validation dataset closely resembles the synthetic dataset. The challenge should generate an optimal model for predicting in-hospital mortality. Following external validation, this model could be used to improve the outcomes for children with proven or suspected sepsis in low- and middle-income settings.

Objectives: Pilot test the nurse-led chronotherapeutic bundle in critically ill children, RESTORE Resilience (R 2 ).

Design: A two-phase cohort study was carried out from 2017 to 2021.

Setting: Two similarly sized and organized PICUs in the United States.

Patients: Children 6 months to 17 years old who were mechanically ventilated for acute respiratory failure.

Interventions: R 2 seven-item chronotherapeutic bundle, including: 1) replication of child's pre-hospital daily routine (i.e., sleep/wake, feeding, activity patterns); 2) cycled day-night light/sound modulation; 3) minimal effective sedation; 4) night fasting with bolus enteral daytime feedings; 5) early progressive mobility; 6) nursing care continuity; and 7) parent diaries.

Measurements and main results: Children underwent environmental (light, sound) and patient (actigraphy, activity log, salivary melatonin, electroencephalogram) monitoring. Parents completed the Child's Daily Routine and Sleep Survey (CDRSS) and Family-Centered Care Scale. The primary outcome was post-extubation daytime activity consolidation (Daytime Activity Ratio Estimate [DARE]). Twenty baseline-phase (2017-2019) and 36 intervention-phase (2019-2021) participants were enrolled. During the intervention phase, nurses used the CDRSS to construct children's PICU schedules. Overall compliance with nurse-implemented R 2 elements 1-5 increased from 18% (interquartile range, 13-30%) at baseline to 63% (53-68%) during the intervention phase ( p < 0.001). Intervention participants were exposed to their pre-hospitalization daily routine ( p = 0.002), cycled day-night light/sound modulation ( p < 0.001), and early progressive mobility on more PICU days ( p = 0.02). Sedation target identification, enteral feeding schedules, and nursing care continuity did not differ between phases. Parent diaries were seldom used. DARE improved during the intervention phase and was higher pre-extubation (median 62% vs. 53%; p = 0.04) but not post-extubation (62% vs. 57%; p = 0.56).

Conclusions: In the PICU, implementation of an individualized nurse-implemented chronotherapeutic bundle is feasible. Children who received the R 2 bundle had increased pre-extubation daytime activity consolidation compared to children receiving usual care. Given variation in protocol adherence, further R 2 testing should include interprofessional collaboration, pragmatic trial design, and implementation science strategies.