Transfusion-Associated Delirium in Children: No Difference Between Short Storage Versus Standard Issue RBCs.

OBJECTIVES: Primary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma. DESIGN: This study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma. SETTING: Twenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial. PATIENTS: Children 3 days to 16 years old who were transfused RBCs within the first 7 days of admission. INTERVENTIONS: Subjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001). CONCLUSIONS: RBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.

Continuous Electroencephalogram and Antiseizure Medication Use in an International Pediatric Traumatic Brain Injury Population.

BACKGROUND: Electrographic seizures are frequent and associated with worse outcomes following traumatic brain injury (TBI). Despite this, the use of continuous electroencephalogram (cEEG) remains low. Our study describes cEEG usage and treatment dosing antiseizure medications (ASMs) in an international pediatric TBI population, hypothesizing that children monitored with cEEG have an increased rate of treatment ASMs because of electrographic seizure detection, compared with children who are not monitored with cEEG. METHODS: This subanalysis of the TBI cohort of the international PANGEA study included children, 7 days to 17 years of age, with acute neurological insults admitted to pediatric intensive care units. We analyzed demographics, injury severity, and therapies including prophylactic or treatment ASMs. We evaluated the relationships between cEEG use, seizure frequency, and receipt of treatment ASMs. [Formula: see text] or Fisher's exact test was used to analyze categorical variables, and the Kruskal-Wallis or Mann-Whitney U-test was used for continuous variables. Multivariable analysis for treatment ASM use was performed using logistic regression. RESULTS: One hundred-twenty-three of 174 patients with TBI were included. Twenty-seven patients (21.9%) underwent cEEG at any point during pediatric intensive care unit admission. Preexisting seizure disorder (18.2% vs. 2.3%, p = 0.014) and neuromuscular blockade use (52.4% vs. 24.1%, p = 0.011) were more frequently observed in the group monitored on cEEG when compared with those that were not. Presenting median Glasgow Coma Scale score was worse in the cEEG group (7 vs. 9, p = 0.044). There was no significant difference in age, use of intracranial pressure monitoring, or hyperosmolar therapy between the cEEG monitored and nonmonitored groups. Patients who were monitored on cEEG were more likely to receive a treatment dose ASM than those without cEEG monitoring (66.7% vs. 28.1%, p = 0.0002). When compared with those without treatment ASM, the treatment ASM group had more electrographic seizures on their first electroencephalogram following injury (51.6% vs. 4%, p = 0.0001) and more clinical seizures (55.8% vs. 0%, p < 0.0001). CONCLUSIONS: Children monitored with cEEG after TBI have an increased prescription of treatment ASMs and clinical and electrographic seizures. The increased rate of treatment ASMs in the cEEG group may indicate increased recognition of electrographic seizures.

Use of Pharmacologic Prophylaxis Against Venous Thromboembolism in Hospitalized Injured Children.

Despite a practice management guideline and risk prediction model for venous thromboembolism (VTE), pediatric-specific evidence on pharmacologic prophylaxis is lacking. In a retrospective study, we characterized receipt of prophylaxis and explored its effectiveness in hospitalized injured patients below 18 years old using data from the Trauma Quality Improvement Program. Concordance of receipt of prophylaxis with guideline and predicted risk of VTE was estimated using κ statistic. Effectiveness was explored using cohorts matched based on the risk prediction model. A total of 11,165 (6.2%) of 180,932 patients received prophylaxis. Those who received prophylaxis were more commonly post-pubertal and more severely injured. Receipt of prophylaxis was fairly concordant with the guideline (κ=0.32) and predicted risk of VTE (κ=0.29). Receipt of prophylaxis was associated with higher rates of VTE likely due to confounding by indication. Low molecular weight heparin seemed more effective against VTE than unfractionated heparin (incidence rate ratio: 0.52; 95% confidence interval: 0.36, 0.75), but less effective when received ≥72 hours after admission to the hospital. We showed that hospitalized injured children did not commonly receive prophylaxis. We also showed that prophylaxis may be effective in hospitalized injured children, but it needs to be proven definitively in a randomized clinical trial.

Coagulation Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Previous criteria for coagulation dysfunction in critically ill children were based mainly on expert opinion. OBJECTIVE: To evaluate current evidence regarding coagulation tests associated with adverse outcomes in children to inform criteria for coagulation dysfunction during critical illness. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 by using a combination of medical subject heading terms and text words to define concepts of coagulation dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION: Studies were included if critically ill children with coagulation dysfunction were evaluated, if performance characteristics of assessment and/or scoring tools to screen for coagulation dysfunction were evaluated, and if outcomes related to mortality or functional status, organ-specific outcomes, or other patient-centered outcomes were assessed. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form, along with risk of bias assessment, by a task force member. RESULTS: The systematic review supports the presence of at least 2 of the following criteria reflecting coagulation dysfunction in the absence of liver dysfunction: platelet count <100 000 cells per µL, international normalized ratio >1.5, fibrinogen level <150 mg/dL, and D-dimer value above 10 times the upper limit of normal, or above the assay's upper limit of detection if this limit is below 10 times the upper limit of normal. LIMITATIONS: The proposed criteria for coagulation dysfunction are limited by the available evidence and will require future validation. CONCLUSIONS: Validation of the proposed criteria and identified scientific priorities will enhance our understanding of coagulation dysfunction in critically ill children.

Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.

Vasoactive-Inotropic Score and Vasoactive-Ventilation-Renal Score as Outcome Predictors for Children on Extracorporeal Membrane Oxygenation.

We aimed to determine the association of vasoactive-inotropic score (VIS) and vasoactive-ventilation-renal (VVR) score with in-hospital mortality and functional outcomes at discharge of children who receive ECMO. A sub-analysis of the multicenter, prospectively collected data by the Collaborative Pediatric Critical Care Research Network (CPCCRN) for Bleeding and Thrombosis on ECMO (BATE database) was conducted. Of the 514 patients who received ECMO across eight centers from December 2012 to February 2016, 421 were included in the analysis. Patients > 18 years of age, patients placed on ECMO directly from cardiopulmonary bypass or as an exit procedure, or patients with an invalid or missing VIS score were excluded. Higher VIS (OR = 1.008, 95% CI: 1.002-1.014, p = 0.011) and VVR (OR: 1.006, 95% CI: 1.001-1.012, p = 0.023) were associated with increased mortality. VIS was associated with worse Pediatric Cerebral Performance Category (PCPC) (OR = 1.027, 95% CI: 1.010-1.044, p = 0.002) and Pediatric Overall Performance Category (POPC) score (OR = 1.023, 95% CI: 1.009-1.038, p = 0.002) at discharge. No association was found between VIS or VVR and Functional Status Score (FSS) at discharge. Using multivariable analyses, controlling for ECMO mode, ECMO location, ECMO indication, primary diagnosis, and chronic diagnosis, extremely high VIS and VVR were still associated with increased mortality.

Association of Fluid Balance and Survival of Pediatric Patients Treated With Extracorporeal Membrane Oxygenation.

The effect of positive fluid balance (FB) on extracorporeal membrane oxygenation (ECMO) outcomes in pediatric patients remains unknown. We sought to evaluate if positive FB in pediatric intensive care unit (PICU) patients with respiratory and/or cardiac failure necessitating ECMO was associated with increased morbidity or mortality. This was a multicenter retrospective cohort study of data from the deidentified PEDiatric ECMO Outcomes Registry (PEDECOR). Patients entered into the database from 2014 to 2017, who received ECMO support, were included. A total of 168 subjects met the study criteria. Univariate analysis showed no significant difference in total FB on ECMO days 1-5 between survivors and non-survivors [median 90 ml/kg (IQR 18-208.5) for survivors vs. median 139.7 ml/kg (IQR 11.2-300.6) for non-survivors, p = 0.334]. There was also no difference in total FB on ECMO days 1-5 in patients with no change in functional outcome as reflected by the Pediatric Outcome Performance Category (POPC) score vs. those who had worsening in POPC score ≥2 at hospital discharge [median 98 ml/kg (IQR 18-267) vs. median 130 ml/kg (IQR 13-252), p = 0.91]. Subjects that required 50 ml/kg or more of blood products over the initial 5 days of ECMO support had an increased rate of mortality with an odds ratio of 5.8 (95% confidence interval of 2.7-12.3; p = 0.048). Our study showed no association of the noted FB with survival after ECMO cannulation. This FB trend was also not associated with POPC at hospital discharge, MV duration, or ECMO duration. The amount of blood product administered was found to be a significant predictor of mortality.

Evaluation of Severity of Illness Scores in the Pediatric ECMO Population.

Though commonly used for adjustment of risk, severity of illness and mortality risk prediction scores, based on the first 24 h of intensive care unit (ICU) admission, have not been validated in the pediatric extracorporeal membrane oxygenation (ECMO) population. We aimed to determine the association of Pediatric Index of Mortality 2 (PIM2), Pediatric Risk of Mortality Score III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores with mortality in pediatric patients on ECMO. This was a retrospective cohort study of children ≤18 years of age included in the Pediatric ECMO Outcomes Registry (PEDECOR) from 2014 to 2018. Logistic regression and Receiver Operating Characteristics (ROC) curves were used to calculate the area under the curve (AUC) to evaluate association of mortality with the scores. Of the 655 cases, 289 (44.1%) did not survive until hospital discharge. AUCs for PIM2, PRISM III, and PELOD predicting mortality were 0.52, 0.52, and 0.51 respectively. PIM2, PRISM III, and PELOD scores are not associated with odds of mortality for pediatric patients receiving ECMO. These scores for a general pediatric ICU population should not be used for prognostication or risk stratification of a select population such as ECMO patients.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III).

BACKGROUND: To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. STUDY DESIGN AND METHODS: This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. RESULTS: A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5 g/dl (10-90th percentile: 6.4-8.8 g/dl), with 45.7% of transfusions being given at 7 to <8 g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. DISCUSSION: Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Transfusion Practices in Pediatric Cardiac Surgery Requiring Cardiopulmonary Bypass: A Secondary Analysis of a Clinical Database.

OBJECTIVES: To describe blood component usage in transfused children with congenital heart disease undergoing cardiopulmonary bypass surgery across perioperative settings and diagnostic categories. DESIGN: Datasets from U.S. hospitals participating in the National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III were analyzed. SETTING: Inpatient admissions from three U.S. hospitals from 2013 to 2016. PATIENTS: Transfused children with congenital heart disease undergoing single ventricular, biventricular surgery, extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight hundred eighty-two transfused patients were included. Most of the 185 children with single ventricular surgery received multiple blood products: 81% RBCs, 79% platelets, 86% plasma, and 56% cryoprecipitate. In the 678 patients undergoing biventricular surgery, 85% were transfused plasma, 75% platelets, 74% RBCs, and 48% cryoprecipitate. All 19 patients on extracorporeal membrane oxygenation were transfused RBCs, plasma, and cryoprecipitate, and 18 were transfused platelets. Intraoperatively, patients commonly received all three components, while postoperative transfusions were predominantly single blood components. Pretransfusion hemoglobin values were normal/low-normal for age for all phases of care for single ventricular surgery (median hemoglobin 13.2-13.5 g/dL). Pretransfusion hemoglobin values for biventricular surgeries were higher intraoperatively compared with other timing (12.2 g/dL vs 11.2 preoperative and postoperative; p < 0.0001). Plasma transfusions for all patients were associated with a near normal international normalized ratio: single ventricular surgeries median international normalized ratio was 1.3 postoperative versus 1.8 intraoperative and biventricular surgeries median international normalized ratio was 1.1 intraoperative versus 1.7 postoperative. Intraoperative platelet transfusions with biventricular surgeries had higher median platelet count compared with postoperative pretransfusion platelet count (244 × 109/L intraoperative vs 69 × 109/L postoperative). CONCLUSIONS: Children with congenital heart disease undergoing cardiopulmonary bypass surgery are transfused many blood components both intraoperatively and postoperatively. Multiple blood components are transfused intraoperatively at seemingly normal/low-normal pretransfusion values. Pediatric evidence guiding blood component transfusion in this population at high risk of bleeding and with limited physiologic reserve is needed to advance safe and effective blood conservation practices.

GCS-Pupil Score Has a Stronger Association with Mortality and Poor Functional Outcome than GCS Alone in Pediatric Severe Traumatic Brain Injury.

BACKGROUND: The Glasgow Coma Scale (GCS), used to classify the severity of traumatic brain injury (TBI), is associated with mortality and functional outcomes. However, GCS can be affected by sedation and neuromuscular blockade. GCS-Pupil (GCS-P) score, calculated as GCS minus Pupil Reactivity Score (PRS), was shown to better predict outcomes in a retrospective cohort of adult TBI patients. We evaluated the applicability of GCS-P to a large retrospective pediatric severe TBI (sTBI) cohort. METHODS: Admissions to pediatric intensive care units in the Virtual Pediatric Systems (VPS, LLC) database from 2010 to 2015 with sTBI were included. We collected GCS, PRS (number of nonreactive pupils), cardiac arrest, abusive head trauma status, illness severity scores, pediatric cerebral performance category (PCPC) score, and mortality. GCS-P was calculated as GCS minus PRS. χ2 or Fisher's exact test and Mann-Whitney U test compared categorical and continuous variables, respectively. Classification and regression tree analysis identified thresholds of GCS-P and GCS along with other independent factors which were further examined using multivariable regression analysis to identify factors independently associated with mortality and unfavorable PCPC at PICU discharge. RESULTS: Among the 2,682 patients included in the study, mortality was 23%, increasing from 4.7% for PRS = 0 to 80% for PRS = 2. GCS-P identified more severely injured patients with GCS-P scores 1 and 2 who had worse outcomes. GCS-P ≤ 2 had higher odds for mortality, OR = 68.4 (95% CI = 50.6-92.4) and unfavorable PCPC, OR = 17.3 (8.1, 37.0) compared to GCS ≤ 5. GCS-P ≤ 2 also had higher specificity and positive predictive value for both mortality and unfavorable PCPC compared to GCS ≤ 5. CONCLUSIONS: GCS-P, by incorporating pupil reactivity to GCS scoring, is more strongly associated with mortality and poor functional outcome at PICU discharge in children with sTBI.

Transfusion practices in a large cohort of hospitalized children.

BACKGROUND: While previous studies have described the use of blood components in subsets of children, such as the critically ill, little is known about transfusion practices in hospitalized children across all departments and diagnostic categories. We sought to describe the utilization of red blood cell, platelet, plasma, and cryoprecipitate transfusions across hospital settings and diagnostic categories in a large cohort of hospitalized children. STUDY DESIGN AND METHODS: The public datasets from 11 US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) were accessed. All nonbirth inpatient encounters of children 0-18 years of age from 2013 to 2016 were included. RESULTS: 61,770 inpatient encounters from 41,943 unique patients were analyzed. Nine percent of encounters involved the transfusion of at least one blood component. RBC transfusions were most common (7.5%), followed by platelets (3.9%), plasma (2.5%), and cryoprecipitate (0.9%). Children undergoing cardiopulmonary bypass were most likely to be transfused. For the entire cohort, the median (interquartile range) pretransfusion laboratory values were as follows: hemoglobin, 7.9 g/dl (7.1-10.4 g/dl); platelet count, 27 × 109 cells/L (14-54 × 109 cells/L); and international normalized ratio was 1.6 (1.4-2.0). Recipient age differences were observed in the frequency of RBC irradiation (95% in infants, 67% in children, p < .001) and storage duration of RBC transfusions (median storage duration of 12 [8-17] days in infants and 20 [12-29] days in children, p < .001). CONCLUSION: Based on a cohort of patients from 2013 to 2016, the transfusion of blood components is relatively common in the care of hospitalized children. The frequency of transfusion across all pediatric hospital settings, especially in children undergoing cardiopulmonary bypass, highlights the opportunities for the development of institutional transfusion guidelines and patient blood management initiatives.

Life-Threatening Bleeding in Children: A Prospective Observational Study.

OBJECTIVES: The purpose of our study was to describe children with life-threatening bleeding. DESIGN: We conducted a prospective observational study of children with life-threatening bleeding events. SETTING: Twenty-four childrens hospitals in the United States, Canada, and Italy participated. SUBJECTS: Children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under massive transfusion protocol were included. INTERVENTIONS: Children were compared according bleeding etiology: trauma, operative, or medical. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, therapies administered, and clinical outcomes were analyzed. Among 449 enrolled children, 55.0% were male, and the median age was 7.3 years. Bleeding etiology was 46.1% trauma, 34.1% operative, and 19.8% medical. Prior to the life-threatening bleeding event, most had age-adjusted hypotension (61.2%), and 25% were hypothermic. Children with medical bleeding had higher median Pediatric Risk of Mortality scores (18) compared with children with trauma (11) and operative bleeding (12). Median Glasgow Coma Scale scores were lower for children with trauma (3) compared with operative (14) or medical bleeding (10.5). Median time from bleeding onset to first transfusion was 8 minutes for RBCs, 34 minutes for plasma, and 42 minutes for platelets. Postevent acute respiratory distress syndrome (20.3%) and acute kidney injury (18.5%) were common. Twenty-eight-day mortality was 37.5% and higher among children with medical bleeding (65.2%) compared with trauma (36.1%) and operative (23.8%). There were 82 hemorrhage deaths; 65.8% occurred by 6 hours and 86.5% by 24 hours. CONCLUSIONS: Patient characteristics and outcomes among children with life-threatening bleeding varied by cause of bleeding. Mortality was high, and death from hemorrhage in this population occurred rapidly.

Variation in Neonatal Transfusion Practice.

OBJECTIVE: To estimate the incidence of blood product transfusion, including red blood cells, platelets, and plasma, and characterize pretransfusion hematologic values for infants during their initial hospitalization after birth. STUDY DESIGN: Retrospective cohort study using data from 7 geographically diverse US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) from 2013 to 2016. Pretransfusion hematologic values were evaluated closest to each transfusion and no more than 24 hours beforehand. RESULTS: Data from 60 243 infants were evaluated. The incidence of any transfusion differed by gestational age (P < .0001), with 80% (95% CI 76%-84%) transfused at <27 weeks of gestation (n = 329) and 0.5% (95% CI 0.5%-0.6%) transfused at ≥37 weeks of gestation (n = 53 919). The median pretransfusion hemoglobin was 11.2 g/dL (10th-90th percentile 8.8-14.1) for the entire cohort, ranging from 10.5 g/dL (8.8-12.3) for infants born extremely preterm at <27 weeks of gestation to 13.0 g/dL (10.5-15.5) for infants born at term. The median pretransfusion platelet count (×109/L) was 71 (10th-90th percentile 26-135) for the entire cohort, and was >45 for all gestational age groups examined. The median pretransfusion international normalized ratio for the entire cohort was 1.7 (10th-90th percentile 1.2-2.8). CONCLUSIONS: There is wide variability in pretransfusion hemoglobin, platelet count, and international normalized ratio values for neonatal transfusions. Our findings suggest that a large proportion of neonatal transfusions in the US are administered at thresholds greater than supported by the best-available evidence and highlight an opportunity for improved patient blood management.

Venovenous Versus Venoarterial Extracorporeal Membranous Oxygenation in Inotrope Dependent Pediatric Patients With Respiratory Failure.

Patients with respiratory failure requiring inotropes or vasopressors are often placed on venoarterial (VA) extracorporeal membrane oxygenation (ECMO), as venovenous (VV) ECMO does not provide direct circulatory support. This retrospective multicenter study compared outcomes for 103 pediatric patients, with hemodynamic compromise, placed on VV ECMO for respiratory failure to those placed on VA ECMO. The primary outcome was survival to hospital discharge. Fifty-seven (55%) study participants were supported on VV ECMO. The two groups had similar PRISM III scores at pediatric intensive care unit (PICU) admission, and vasoactive-inotropic scores at ECMO cannulation. More VV ECMO patients received inhaled nitric oxide (iNO) (54.4 vs. 34.8%; p = 0.04) and had a higher oxygenation index (median 41.5 vs. 19.5; p = 0.04) pre-ECMO. More VA ECMO patients had cardiac dysfunction and cardiac arrest pre-ECMO (50 vs. 14%; p < 0.0001). In univariable analysis, survival to hospital discharge was higher in the VV vs. VA ECMO group (72 vs. 44%; p = 0.005), however, in multivariable models, cannulation type was confounded by cardiopulmonary resuscitation and was not independently associated with survival. VV survivors had longer ECMO duration compared with VA survivors (median, 7 vs. 4.5 days; p = 0.036) but similar PICU and hospital days. No significant difference was noted in functional outcomes or comorbidities at discharge. Cannulation type is not independently associated with survival to hospital discharge in pediatric patients on vasoactive infusions at the time of ECMO cannulation for respiratory indications.

Age-Dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-Associated Thrombosis in Critically Ill Children: A Post Hoc Analysis of a Bayesian Phase 2b Randomized Clinical Trial.

OBJECTIVES: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children. DESIGN: Post hoc analysis of a Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with newly inserted central venous catheter. INTERVENTIONS: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2-0.5 international units/mL versus usual care. MEASUREMENTS AND MAIN RESULTS: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37-2.44) in infants and 0.24 (95% credible interval, 0.04-0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78-437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7-74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17-61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count. CONCLUSIONS: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin.

Risks of venous thrombosis and bleeding in critically ill adolescents after trauma or major surgery.

BACKGROUND: The risks of venous thromboembolism (VTE) and bleeding in critically ill adolescents based on interventions received and anatomic site of trauma or major surgery may identify a cohort eligible for enrollment in a trial of pharmacologic prophylaxis. METHODS: This retrospective cohort study using the Virtual Pediatric Systems database included adolescents admitted to pediatric intensive care units after trauma or major surgery between 2013 and 2017. Mixed effects logistic regression was used to determine the adjusted risks of VTE and bleeding with central venous catheterization (CVC), mechanical ventilation (MV) and anatomic site of trauma or major surgery. The adjusted risks were used to identify the cohort eligible for enrollment. MEASUREMENTS AND MAIN RESULTS: VTE developed in 212 (0.8%) of 27,647 adolescents. The adjusted risk of VTE was >2% with CVC and 2 or more of MV and trauma or major surgery to the brain or abdomen. Excluding those with bleeds present on admission or at high risk of bleeding, 375 (1.4%) adolescents would be eligible for enrollment. CONCLUSIONS: VTE is generally uncommon in adolescents after trauma or major surgery. The small proportion of adolescents who are at high risk of VTE and at low risk of bleeding impacts the feasibility of a trial. LEVEL OF EVIDENCE: Prognostic Study Level II.

Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial.

OBJECTIVES: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children. DESIGN: Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding. INTERVENTION: Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm). MEASUREMENTS AND MAIN RESULTS: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms. CONCLUSIONS: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.