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.

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.

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.

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.

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.

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.

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 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.

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.

Rates of Venous Thromboembolism and Central Line-Associated Bloodstream Infections Among Types of Central Venous Access Devices in Critically Ill Children.

OBJECTIVES: Central venous access devices, including peripherally inserted central catheters and central venous catheters, are often needed in critically ill patients, but also are associated with complications, including central-line associated bloodstream infections and venous thromboembolism. We compared different central venous access device types and these complications in the PICU. DESIGN: Multicenter, cohort study. SETTING: One hundred forty-eight participating Virtual PICU Systems, LLC, hospital PICU sites. PATIENTS: Pediatric patients with central venous access placed from January 1, 2010, to December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient and central venous access device variables postulated to be associated with central-line associated bloodstream infection and venous thromboembolism were included. Data were analyzed using Pearson chi-square test or Fisher exact test for categorical variables, Mann-Whitney U test for continuous variables, and logistic regression and classification trees for multivariable analysis that examined significant predictors of venous thromboembolism or central-line associated bloodstream infection. Analysis included 74,196 first lines including 4,493 peripherally inserted central catheters and 66,194 central venous catheters. An increased rate of venous thromboembolism (peripherally inserted central catheter: 0.93%, central venous catheter: 0.52%; p = 0.001) (peripherally inserted central catheter: 8.65/1,000 line days, central venous catheter: 6.29/1,000 line days) and central-line associated bloodstream infection (peripherally inserted central catheter: 0.73%, central venous catheter: 0.24%; p = 0.001) (peripherally inserted central catheter: 10.82/1,000 line days, central venous catheter: 4.97/1,000 line days) occurred in peripherally inserted central catheters. In multivariable analysis, central venous catheters had decreased association with central-line associated bloodstream infection (odds ratio, 0.505; 95% CI, 0.336-0.759; p = 0.001) and venous thromboembolism (odds ratio, 0.569; 95% CI, 0.330-0.982; p = 0.043) compared with peripherally inserted central catheters. CONCLUSIONS: Peripherally inserted central catheters are associated with higher rates of central-line associated bloodstream infection and venous thromboembolism than central venous catheters in children admitted to the PICU.

Outcomes of pediatric patients with oncologic disease or following hematopoietic stem cell transplant supported on extracorporeal membrane oxygenation: The PEDECOR experience.

BACKGROUND: Outcomes for patients with oncologic disease and/or after hematopoietic stem cell transplant (HSCT) requiring intensive care unit admission have improved, but indications for and outcomes after extracorporeal membrane oxygenation (ECMO) support in this population are poorly characterized. PROCEDURE: We analyzed data from consecutive patients < 18 years with oncologic disease and/or after HSCT reported to a pediatric ECMO registry by nine pediatric centers in the United States between 2011 and 2018. RESULTS: We identified 18 ECMO patients with oncologic disease and/or HSCT, and 415 ECMO controls matched with a propensity score algorithm based on age, gender, race, severity of illness at admission, and reason for ECMO. The primary indication for ECMO was respiratory failure in 66.7% in the oncologic disease and/or HSCT group, and in 70.7% in the matched ECMO control group. Eleven of 18 patients survived to hospital discharge (61.1%), similar to the matched control group (60.8%), P = 0.979. Children with oncologic disease and/or HSCT had lower mean platelet counts during ECMO and received higher volumes of platelets compared with the control group, mean 14.6 mL/kg/day (standard deviations [SD], 9.8) versus mean 9.3 mL/kg/day (SD, 10.4), P = 0.001. Of the 11 surviving children with oncologic disease and/or HSCT, five sustained new neurologic disorders (45.5%) versus 45 of 222 (20.3%) in the control group, P = 0.061. Bleeding complications were similar in the two groups. CONCLUSIONS: Outcomes of patients with oncologic disease and/or HSCT supported on ECMO in the current era are not significantly different compared with matched ECMO controls and are improved from previously published reports.

Enteral Nutrition Initiation in Children Admitted to Pediatric Intensive Care Units After Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and long-term disability among injured children. Early feeding has been shown to improve outcomes in adults, with some similar evidence in children with severe TBI. We aimed to examine the current practice of initiation of enteral nutrition in children with TBI and to evaluate the risk factors associated with delayed initiation of enteral nutrition. METHODS: This retrospective, multicenter study used the Pediatric Trauma Assessment and Management Database including all children with head trauma discharged from five pediatric intensive care units (PICU) at pediatric trauma centers between January 1, 2013 and December 31, 2013. We compared demographics, injury and procedure data, time to initiation of nutrition, and injury and illness severity scores between patients who received enteral nutrition early (≤ 48 h) and late (> 48 h). Fisher's exact and Mann-Whitney U tests compared discrete and continuous variables. Univariate and multivariable analyses evaluated variables associated with delayed initiation of feeding. Outcomes of interest included mortality, complications, ventilator days, hospital and ICU length of stay, and functional status at ICU discharge. RESULTS: In the 416 patients in the study, the overall mortality was 2.6%. The majority of patients (83%; range 69-88% between five sites, p = 0.0008) received enteral nutrition within 48 h of PICU admission. Lower Glasgow Coma Scale scores and higher Injury Severity Score (ISS) were independently associated with delayed initiation of enteral nutrition. Delayed enteral nutrition was independently associated with worse functional status at PICU discharge (p = 0.02) but was not associated with mortality or increased length of stay. CONCLUSIONS: Children with severe TBI and higher ISS were more likely to have delayed initiation of enteral nutrition. Delayed enteral nutrition was an independent risk factor for worse functional status at ICU discharge for the entire cohort, but not for the severe TBI group.

Central Venous Catheter-associated Venous Thromboembolism in Children With Hematologic Malignancy.

In pediatric oncology, the diagnosis of a hematologic malignancy and presence of a central venous catheter (CVC) have been identified as significant risk factors for the development of a venous thromboembolism (VTE). There remain little data regarding CVC factors associated with CVC-related VTE. Using the VTE and oncology database in a quaternary care center, a retrospective cohort study was conducted in children below 18 years old with hematologic cancer from November 5, 2012 to April 4, 2016. Patient, CVC factors, and VTE occurrence were analyzed to identify significant patient and CVC factors associated with the development of clinically identified CVC-related VTE. Utilizing the χ, Mann-Whitney, and the Fisher exact tests, patient factors were compared across VTE yes/no groups. Of the 198 study patients, 22 VTE cases were identified. Eighteen VTE events were CVC-associated, occurring in 9% of study population. Peripherally inserted central catheter lines and older ages were associated with VTE. The use of tissue-plasminogen activator for CVC occlusion was associated with decreased VTE rates, suggesting a protective potential.

Comparison of Complication Rates of Central Venous Catheters Versus Peripherally Inserted Central Venous Catheters in Pediatric Patients.

OBJECTIVES: The purpose of our study is to compare the rate of central line-associated blood stream infections and venous thromboembolism in central venous catheters versus peripherally inserted central catheters in hospitalized children. There is a growing body of literature in adults describing an increased rate of venous thromboembolisms and similar rates of central line-associated blood stream infection associated with peripherally inserted central catheters versus central venous catheters. It is not known if the rate of central line-associated blood stream infection and venous thromboembolism differs between peripherally inserted central catheters and central venous catheters in children. Based on current adult literature, we hypothesize that central line-associated blood stream infection rates for peripherally inserted central catheters and central venous catheters will be similar, and the rate of venous thromboembolism will be higher for peripherally inserted central catheters versus central venous catheters. DESIGN: This is a cohort study using retrospective review of medical records and prospectively collected hospital quality improvement databases. SETTING: Quaternary-care pediatric hospital from October 2012 to March 2016. PATIENTS: All patients age 1 day to 18 years old with central venous catheters and peripherally inserted central catheters placed during hospital admission over the study dates were included. Central venous catheters that were present upon hospital admission were excluded. The primary outcomes were rate of central line-associated blood stream infection and rate of venous thromboembolism. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,709 catheters included in the study, 1,126 were peripherally inserted central catheters and 1,583 were central venous catheters. Peripherally inserted central catheters demonstrated a higher rate of both infection and venous thromboembolism than central venous catheters in all reported measures. In multivariable analysis, peripherally inserted central catheters had increased association with central line-associated blood stream infection (odds ratio of 3.15; 95% CI, 1.74-5.71; p = 0.0002) and increased association with venous thromboembolism (odds ratio of 2.71; 95% CI, 1.65-4.45; p < 0.0001) compared with central venous catheters. CONCLUSIONS: Rates of central line-associated blood stream infection and venous thromboembolism were higher in hospitalized pediatric patients with peripherally inserted central catheters as compared to central venous catheters. Our study confirms the need for further investigation into the safety of central access devices to assist in proper catheter selection.

Multicenter Review of Current Practices Associated With Venous Thromboembolism Prophylaxis in Pediatric Patients After Trauma.

OBJECTIVES: Frequency of venous thromboembolism in pediatric trauma patients admitted to PICUs is not insignificant, ranging up to 6%. Risk factors have been identified in this population. However, there is little consensus of actual venous thromboembolism prophylaxis practice. We examined factors associated with venous thromboembolism prophylaxis in PICUs. DESIGN: A retrospective study evaluating associations with mechanical venous thromboembolism prophylaxis, pharmacologic venous thromboembolism prophylaxis, or dual therapy (DUAL) prophylaxis compared with no venous thromboembolism prophylaxis. Multivariable logistic regression explored the relationship between prophylaxis type and selected covariates with stepwise selection method to identify the independent predictors of venous thromboembolism prophylaxis utilization. SETTING: Five level I/II pediatric trauma centers in the United States. PATIENTS: Children less than 18 years from January 1, 2013, to December 31, 2013, admitted to the PICU after a trauma, identified through combined trauma registry and Virtual Pediatric Systems database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six hundred ninety-two patients were included in the database, with 55 excluded for missing data. Of the remaining 637 patients, 538 (84.5%) had no venous thromboembolism prophylaxis by 48 hours, 77 (12.1%) had only mechanical venous thromboembolism prophylaxis, 11 (1.7%) had DUAL, and 11 (1.7%) had pharmacologic venous thromboembolism prophylaxis alone. Multivariable analysis showed increased age, and orthopedic procedure was associated with all forms of prophylaxis. Orthopedic procedures were associated with higher utilization of dual prophylaxis use (odds ratio, 5.2; 95% CI, 1.2-21.8), pharmacologic venous thromboembolism prophylaxis (odds ratio, 8.5; 95% CI, 2.3-31.7), and mechanical venous thromboembolism prophylaxis (odds ratio, 2.2; 95% CI, 1.1-4.2) alone. Brain/spinal cord procedures (odds ratio, 3.7; 95% CI, 1.9-7.3) and abdominal procedures (odds ratio, 6.6; 95% CI, 2.5-17.1) were associated with mechanical venous thromboembolism prophylaxis. Head injury was associated with a decreased use of any prophylaxis (odds ratio, 0.5; 95% CI, 0.3-0.9). Patient comorbidities were associated with decreased use of mechanical venous thromboembolism prophylaxis (odds ratio, 0.5; 95% CI, 0.3-1.0). CONCLUSIONS: Pharmacologic venous thromboembolism prophylaxis is not common in critically ill children after trauma. Patient age, orthopedic and vascular procedures, and higher injury severity are associated with pharmacologic venous thromboembolism prophylaxis.

Impact of the Timing of Placement of an Intracranial Pressure Monitor on Outcomes in Children with Severe Traumatic Brain Injury.

BACKGROUND: Severe traumatic brain injury (sTBI) is the leading cause of morbidity and mortality from trauma. Brain Trauma Foundation guidelines recommend intracranial pressure (ICP) monitoring in sTBI. We hypothesized that early ICP monitor placement was associated with better outcomes in children. METHODS: This was a retrospective study of children with sTBI admitted to the participating pediatric intensive care units (PICUs) and entered into the Virtual Pediatric Systems (VPS), LLC, database between 1 January 2010 and 31 December 2015. We compared outcomes of patients who had an ICP monitor placed early (≤6 h from PICU admission) to those with later placement (> 6 to < 72 h). We collected demographics, diagnoses, procedure data, illness severity scores, outcomes, and site data. Multivariable regression analysis was used to identify variables independently associated with outcomes. RESULTS: Twenty-seven percent of 3,608 patients with sTBI underwent ICP monitoring, 355 in the early and 156 in the later ICP monitoring groups, respectively. A higher proportion of patients in the early ICP monitoring group had worse markers of illness/injury severity; unadjusted analysis showed higher mortality in this group (31.3 vs. 21.8%, p = 0.029). Multivariable regression analysis showed that ICP monitoring was not independently associated with any of the outcomes. CONCLUSION: Time to ICP monitoring was not associated with outcomes after pediatric sTBI.

Low near infrared spectroscopic somatic oxygen saturation at admission is associated with need for lifesaving interventions among unplanned admissions to the pediatric intensive care unit.

To investigate the association between low near infrared spectroscopy (NIRS) somatic oxygen saturation (<70%) at admission and the need for lifesaving interventions (LSI) in the initial 24 h of a PICU admission. Retrospective chart review of all unplanned admissions to the pediatric intensive care unit (PICU) with NIRS somatic oxygen saturation data available within 4 h of admission, excluding admissions with a cardiac diagnosis. LSI data were collected for the first 24 h after admission. Hemodynamic parameters, laboratory values, illness severity scores and diagnoses were collected. Included PICU admissions were stratified by lowest NIRS value in the first 4 h after admission: low NIRS (<70%) and normal NIRS (≥70%) groups. Rate of LSI from 4 h to 24 h was compared between the two groups. Association of LSI with NIRS saturation and other clinical and laboratory parameters was measured by univariate and multivariate methods. We reviewed 411 consecutive unplanned admissions to the PICU of which 184 (44%) patients underwent NIRS monitoring. A higher proportion of patients who underwent somatic NIRS monitoring required LSIs compared to those without NIRS monitoring (36.4 vs 5.7% respectively, p < 0.0001). The proportion of patients who required LSI was higher in the group with low NIRS (<70%) within the first 4 h compared to those with normal NIRS (≥70%) (77.1 vs 22.1%, p < 0.0001). Fluid resuscitation, blood products and vasoactive medications were the most common LSIs. Multivariable modeling showed NIRS < 70% and heart rate > 2SD for age to be associated with LSIs. ROC curve analysis of the combination of NIRS < 70% and HR >2SD for age had an area under the curve of 0.79 with 78% sensitivity and 76% specificity for association with LSI. Compared to the normal NIRS group, the low NIRS group had higher mortality (10.4 vs 0.7%, p = 0.005) and longer median hospital length of stay (2.9 vs 1.6 days, p < 0.0001). Low somatic NIRS oxygen saturation (<70%) in the first 4 h of an unplanned PICU admission is associated with need for higher number of subsequent lifesaving interventions up to 24 h after admission. Noninvasive, continuous, somatic NIRS monitoring may identify children at high risk of medical instability.