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Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Background: Central venous catheter (CVC) use is common in the management of critically ill children, especially those with congenital heart disease. CVCs are known to augment the risk of deep vein thrombosis (DVT), but data on CVC-associated DVTs in the pediatric cardiac intensive care unit (CICU) are limited. In this study, we aim to identify the incidence of and risk factors for CVC-related DVT in this high-risk population, as its complications are highly morbid., Materials and Methods: The PC4 database and a radiologic imaging database were retrospectively reviewed for the demographics and outcomes of patients admitted to the Texas Children's Hospital CICU requiring CVC placement, as well as the incidence of DVT and its complications., Results: Between January 2017 and December 2017, 1215 central lines were placed over 851 admissions. DVT was diagnosed in 8% of admissions with a CVC, 29% of which demonstrated thrombus in the inferior vena cava. The risk factors significantly associated with DVT included the presence of >1 line, higher total line hours, longer intubation times, and extended CICU stay. A diagnosis of low cardiac output syndrome, sepsis, central line-associated bloodstream infection, and cardiac catheterization were also significant risk factors. Interestingly, cardiac surgery with cardiopulmonary bypass appeared to be protective of clot development. DVT was a highly significant risk factor for mortality in these patients., Conclusions: CVC-related DVTs in critically ill children with congenital heart disease are associated with higher risks of morbidity and mortality, highlighting the need for well-designed studies to determine the best preventative and treatment strategies and to establish guidelines for appropriate monitoring and follow-up of these patients., (Published by Elsevier Inc.)

Objectives: Acetaminophen is ubiquitously used as antipyretic/analgesic administered IV to patients undergoing surgery and to critically ill patients when enteral routes are not possible. Widely believed to be safe and free of adverse side effects, concerns have developed in adult literature regarding the association of IV acetaminophen and transient hypotension. We hypothesize that there are hemodynamic effects after IV acetaminophen in the PICU and assess the prevalence of such in a large pediatric cardiovascular ICU population using high-fidelity data., Design: Observational study analyzing an enormous set of continuous physiologic data including millions of beat to beat blood pressures surrounding medication administration., Setting: Quaternary pediatric cardiovascular ICU between January 1, 2013, and November 13, 2017., Patients: All patients less than or equal to 18 years old who received IV acetaminophen. Mechanical support devices excluded., Interventions: None., Measurements and Main Results: Physiologic vital sign data were analyzed in 5-minute intervals starting 60 minutes before through 180 minutes after completion. Hypotension defined as mean arterial pressure -15% from baseline and relative hypotension defined -10%. Only doses where patients received no other medications, including vasopressors, within the previous hour were included. t test and a correlation matrix were used to eliminate correlated factors before a logistic regression analysis was performed. Six-hundred eight patients received 777 IV acetaminophen doses. Median age was 8.8 months (interquartile range, 2-62 mo) with a dose of 12.5 mg/kg (interquartile range, 10-15 mg/kg). Data were normalized for age and reference values. One in 20 doses (5%) were associated with hypotension, and one in five (20%) associated with relative hypotension. Univariate analysis revealed hypotension associated with age, baseline mean arterial pressure, and skin temperature (p = 0.05, 0.01, and 0.09). Logistic regression revealed mean arterial pressure (p = 0.01) and age (p = 0.05) remained predictive for hypotension., Conclusions: In isolation of other medication, a hemodynamic response to IV acetaminophen has a higher prevalence in critically ill children with cardiac disease than previously thought and justifies controlled studies in the perioperative and critical care setting. The added impact on individual patient hemodynamics and physiologic instability will require further study.

Objectives: Children with medical cardiac disease experience poorer survival to hospital discharge after cardiopulmonary arrest compared with children with surgical cardiac disease. Limited literature exists describing epidemiology and factors associated with mortality in this heterogeneous population. We aim to evaluate the clinical characteristics and outcomes after cardiopulmonary arrest in medical cardiac patients., Design: We performed a retrospective review of pediatric cardiac patients who underwent cardiopulmonary resuscitation in a tertiary care cardiac ICU. Surgical cardiac patients underwent cardiac surgery immediately prior to ICU admission. Nonsurgical cardiac patients were divided into two groups based on the presence of congenital heart disease: congenital heart disease medical or noncongenital heart disease medical. Clinical and outcome variables were collected. Primary outcome was survival to hospital discharge., Settings: Texas Children's Hospital cardiac ICU., Patients: Patients admitted to Texas Children's Hospital cardiac ICU between January 2011 and December 2016., Interventions: None., Measurements and Main Results: Of 150 cardiopulmonary arrest events reviewed, 90 index events were included (46 surgical, 26 congenital heart disease medical, and 18 noncongenital heart disease medical). There was no difference in primary outcome among the three groups. The absence of an epinephrine infusion precardiopulmonary arrest was associated with increased odds of survival in the congenital heart disease medical group (p = 0.03). Noncongenital heart disease medical patients experienced pulseless ventricular tachycardia/ventricular fibrillation more frequently than congenital heart disease medical patients (p = 0.02). Congenital heart disease medical patients had trends toward longer cardiac arrest durations, higher prevalence of neurologic sequelae postcardiopulmonary arrest, and higher mortality when extracorporeal support at cardiopulmonary resuscitation was employed., Conclusions: Although trends in first documented rhythm, neurologic sequelae, and inotropic support prior to cardiopulmonary arrest were noted between groups, no significant differences in survival after cardiac arrest were seen. Larger scale studies are needed to better describe factors associated with cardiopulmonary arrest as well as survival in heterogeneous medical cardiac populations.

Objective: The development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock., Design: Candidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects., Setting: Multiple PICUs in the United States., Interventions: None other than standard care., Measurements and Main Results: The decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91-0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72-0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk., Conclusions: We have derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation.

Introduction: The intrinsic heterogeneity of clinical septic shock is a major challenge. For clinical trials, individual patient management, and quality improvement efforts, it is unclear which patients are least likely to survive and thus benefit from alternative treatment approaches. A robust risk stratification tool would greatly aid decision-making. The objective of our study was to derive and test a multi-biomarker-based risk model to predict outcome in pediatric septic shock., Methods: Twelve candidate serum protein stratification biomarkers were identified from previous genome-wide expression profiling. To derive the risk stratification tool, biomarkers were measured in serum samples from 220 unselected children with septic shock, obtained during the first 24 hours of admission to the intensive care unit. Classification and Regression Tree (CART) analysis was used to generate a decision tree to predict 28-day all-cause mortality based on both biomarkers and clinical variables. The derived tree was subsequently tested in an independent cohort of 135 children with septic shock., Results: The derived decision tree included five biomarkers. In the derivation cohort, sensitivity for mortality was 91% (95% CI 70 - 98), specificity was 86% (80 - 90), positive predictive value was 43% (29 - 58), and negative predictive value was 99% (95 - 100). When applied to the test cohort, sensitivity was 89% (64 - 98) and specificity was 64% (55 - 73). In an updated model including all 355 subjects in the combined derivation and test cohorts, sensitivity for mortality was 93% (79 - 98), specificity was 74% (69 - 79), positive predictive value was 32% (24 - 41), and negative predictive value was 99% (96 - 100). False positive subjects in the updated model had greater illness severity compared to the true negative subjects, as measured by persistence of organ failure, length of stay, and intensive care unit free days., Conclusions: The pediatric sepsis biomarker risk model (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl) reliably identifies children at risk of death and greater illness severity from pediatric septic shock. PERSEVERE has the potential to substantially enhance clinical decision making, to adjust for risk in clinical trials, and to serve as a septic shock-specific quality metric.

Objective: Recently, there has been a shift toward care of children undergoing heart surgery in dedicated pediatric cardiac intensive care units (CICU). The impact of this trend on patient outcomes is unclear. We evaluated postoperative outcomes associated with a CICU versus other ICU models., Patients and Methods: Society of Thoracic Surgeons Congenital Heart Surgery Database participants (2007-2009) who completed an ICU survey were included. In multivariable analysis, we evaluated outcomes associated with a CICU versus other ICUs, adjusting for center volume, patient factors, and Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery surgical risk category., Results: A total of 20 922 patients (47 centers; 25 with a CICU) were included. Overall unadjusted mortality was 3.8%, median length of stay was 6 days (interquartile range: 4-13), and 21% had 1 or more complications. In multivariable analysis, there was no difference in mortality comparing CICUs versus other ICUs (odds ratio: 0.88 [95% confidence interval: 0.65-1.19]). In stratified analysis, CICUs were associated with lower mortality only among those in Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery category 3 (odds ratio: 0.47 [95% confidence interval: 0.25-0.86]), primarily related to atrioventricular canal repair and arterial switch operation. There was no difference in length of stay or complications overall or in stratified analysis., Conclusions: We were not able to detect a difference in postoperative morbidity or mortality associated with the presence of a dedicated CICU for children undergoing heart surgery. There may be a survival benefit in certain subgroups .