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Thursday, June 27, 2019

Pediatric Critical Care Medicine

The Base Deficit, International Normalized Ratio, and Glasgow Coma Scale (BIG) Score, and Functional Outcome at Hospital Discharge in Children With Traumatic Brain Injury
Objectives: To examine the association of the base deficit, international normalized ratio, and Glasgow Coma Scale (BIG) score on emergency department arrival with functional dependence at hospital discharge (Pediatric Cerebral Performance Category ≥ 4) in pediatric multiple trauma patients with traumatic brain injury. Design: A retrospective cohort study of a pediatric trauma database from 2001 to 2018. Setting: Level 1 trauma program at a university-affiliated pediatric institution. Patients: Two to 17 years old children sustaining major blunt trauma including a traumatic brain injury and meeting trauma team activation criteria. Interventions: None. Measurements and Main Results: Two investigators, blinded to the BIG score, determined discharge Pediatric Cerebral Performance Category scores. The BIG score was measured on emergency department arrival. The 609 study patients were 9.7 ± 4.4 years old with a median Injury Severity Score 22 (interquartile range, 12). One-hundred seventy-one of 609 (28%) had Pediatric Cerebral Performance Category greater than or equal to 4 (primary outcome). The BIG constituted a multivariable predictor of Pediatric Cerebral Performance Category greater than or equal to 4 (odds ratio, 2.39; 95% CI, 1.81–3.15) after adjustment for neurosurgery requirement (odds ratio, 2.83; 95% CI, 1.69–4.74), pupils fixed and dilated (odds ratio, 3.1; 95% CI, 1.49–6.38), and intubation at the scene or referral hospital (odds ratio, 2.82; 95% CI, 1.35–5.87) and other postulated predictors of poor outcome. The area under the BIG receiver operating characteristic curve was 0.87 (0.84–0.90). Using an optimal BIG cutoff less than or equal to 8, sensitivity and negative predictive value for functional dependence at discharge were 93% and 96%, respectively, compared with a sensitivity of 79% and negative predictive value of 91% with Glasgow Coma Scale less than or equal to 8. In children with Glasgow Coma Scale 3, the BIG score was associated with brain death (odds ratio, 2.13; 95% CI, 1.58–2.36). The BIG also predicted disposition to inpatient rehabilitation (odds ratio, 2.26; 95% CI, 2.17–2.35). Conclusions: The BIG score is a simple, rapidly obtainable severity of illness score that constitutes an independent predictor of functional dependence at hospital discharge in pediatric trauma patients with traumatic brain injury. The base deficit, international normalized ratio, and Glasgow Coma Scale score may benefit Trauma and Neurocritical care programs in identifying ideal candidates for traumatic brain injury trials within the therapeutic window of treatment. Presented, in part, as oral presentations at the: 1) Trauma Association of Canada meeting, Toronto, ON, Canada, February 23, 2018; and 2) Pediatric Academic Societies meeting, Toronto, ON, Canada, May 6, 2018. Drs. Davis, Hochstadter, and Schuh conceived the study and wrote the protocol. Dr. Davis supervised data collection by Drs. Hochstadter and Daya. Mr. Stephens performed the data analysis. Drs. Davis, Hochstadter, and Schuh drafted the article and Drs. Davis, Hochstadter, Daya, Kulkarni, Wales, and Schuh contributed substantially to its revision. All authors take responsibility for the article as a whole. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Adrienne Davis, MD, MSc, FRCPC, Division of Pediatric Emergency Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. E-mail: adrienne.davis@sickkids.ca ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass
Objectives: Cardiopulmonary bypass–induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants. Design: Single-center prospective observational cohort pilot study. Setting: Pediatric cardiac ICU at a tertiary children's hospital. Patients: Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion. Intervention: None. Measurements and Main Results: Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2–4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2–4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R2 = 0.43; p = 0.008). Conclusions: Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes. The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government. Dr. Krispinsky is a military service member. This work was prepared as part of his official duties. Title 17 U.S.C. 105 provides that "Copyright protection under this title is not available for any work of the U.S. Government." Title 17 U.S.C. 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Supported, in part, by grants from Vanderbilt University Medical Center. Dr. Stark is supported by a grant from the National Institute of General Medical Sciences (K08 GM117367). Dr. Krispinsky disclosed government work. Dr. Stark's institution received funding from the National Institutes of Health (NIH), and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: luke.t.krispinsky.mil@mail.mil Address requests for reprints to: Fred S. Lamb, MD, PhD, Pediatric Critical Care, Vanderbilt Children's Hospital, 2200 Children's Way, 5111 Doctors' Office Tower, Nashville, TN 37232. E-mail: fred.s.lamb@vanderbilt.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Current Epidemiology of Vocal Cord Dysfunction After Congenital Heart Surgery in Young Infants
Objectives: Surgery of the aortic arch poses risk of recurrent laryngeal nerve injury due to the anatomic proximity and can manifest as vocal cord dysfunction after surgery. We assessed risk factors for vocal cord dysfunction and calculated surgical procedure associated rates in young infants after congenital heart surgery. Design: Cross section analysis. Setting: Forty-four children's hospitals reporting administrative data to Pediatric Health Information System. Participants: Cardiac surgical patients less than or equal to 90 days old and discharged between January 2004 and June 2014. Interventions: None. Measurements and Main Results: Overall, 2,319 of 46,567 subjects (5%) had vocal cord dysfunction, increasing from 4% to 7% over the study period. Of those with vocal cord dysfunction, 75% had unilateral partial paralysis. Vocal cord dysfunction was significantly more common in newborn infants (74%), those with aortic arch procedures (77%) and with greater surgical complexity. Rates of vocal cord dysfunction ranged from 0.7% to 22.4% across surgical procedure groups. Vocal cord dysfunction was significantly associated with greater use of: prolonged mechanical ventilation (53% vs 40%), diaphragmatic plication (3% vs 1%), feeding tube use (32% vs 8%), surgical airways (4% vs 2%), and prolonged length of stay (44 vs 21 d). Vocal cord dysfunction testing increased significantly over the study (6–14 %), and vocal cord dysfunction diagnosis increased almost two-fold (odds ratio, 1.9; 95% CI, 1.7–2.1) comparing the last to first study quarters with the increase in vocal cord dysfunction diagnosis occurring predominately in surgeries to the aortic arch supported by cardiopulmonary bypass. However, aortic procedures without cardiopulmonary bypass and nonaortic arch procedures were common surgeries accounting for 27% and 23% of vocal cord dysfunction cases despite low overall vocal cord dysfunction rates (3.7% and 2.6%). Conclusions: Vocal cord dysfunction complicated all cardiac surgical procedures among infants including those without aortic arch involvement. Increased efforts to determine appropriate indications for prevention, screening and treatment of vocal cord dysfunction among young infants after congenital heart surgery are needed. This work was performed at the University of Utah. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http:/journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Susan.Bratton@hsc.utah.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Anemia at Discharge From PICU: A Bicenter Descriptive Study
Objective: To determine the prevalence and risk markers of anemia at PICU discharge. Design: Bicenter retrospective cohort study. Setting: Two multidisciplinary French PICUs. Patients: All children admitted during a 5-year period, staying in the PICU for at least 2 days, and for whom a hemoglobin was available at PICU discharge. Interventions: None. Measurements and Main Results: Patient, admission, and PICU stay characteristics were retrospectively collected in the electronic medical records of each participating PICU. Anemia was defined according to the World Health Organization criteria. Among the 3,170 patients included for analysis, 1,868 (58.9%) were anemic at discharge from PICU. The proportion of anemic children differed between age categories, whereas the median hemoglobin level did not exhibit significant variations according to age. After multivariate adjustment, anemia at PICU admission was the strongest predictor of anemia at PICU discharge, and the strength of this association varied according to age (interaction). Children anemic at PICU admission had a reduced risk of anemia at PICU discharge if transfused with RBCs during the PICU stay, if less than 6 months old, or if creatinine level at PICU admission was low. Children not anemic at PICU admission had an increased risk of anemia at PICU discharge if they were thrombocytopenic at PICU admission, if they had higher C-reactive protein levels, and if they received plasma transfusion, inotropic/vasopressor support, or mechanical ventilation during the PICU stay. Conclusions: Anemia is frequent after pediatric critical illness. Anemia status at PICU admission defines different subgroups of critically ill children with specific prevalence and risk markers of anemia at PICU discharge. Further studies are required to confirm our results, to better define anemia during pediatric critical illness, and to highlight the causes of post-PICU stay anemia, its course, and its association with post-PICU outcomes. This work was performed at the Hôpital Universitaire Jeanne de Flandre, Service de Réanimation Pédiatrique 2, Avenue Eugène Avinée, 59037 Lille Cedex, France, and Hôpital Universitaire Femme Mère Enfant, Hospices Civils de Lyon, Service de Réanimation Pédiatrique, 59, Boulevard Pinel, 69677 Lyon-Bron, France. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: pierre.demaret@chc.be ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Epidemiologic Trends of Adoption of Do-Not-Resuscitate Status After Pediatric In-Hospital Cardiac Arrest
Objectives: To evaluate the prevalence of do-not-resuscitate status, assess the epidemiologic trends of do-not-resuscitate status, and assess the factors associated with do-not-resuscitate status in children after in-hospital cardiac arrest using large, multi-institutional data. Design: Generalized estimating equations logistic regression model was used to evaluate the trends of do-not-resuscitate status and evaluate the factors associated with do-not-resuscitate status after cardiac arrest. Setting: American Heart Association's Get With the Guidelines-Resuscitation Registry. Patients: Children (< 18 yr old) with an index in-hospital cardiac arrest and greater than or equal to 1 minute of documented chest compressions were included (2006–2015). Patients with no return of spontaneous circulation after cardiac arrest were excluded. Interventions: None. Measurements and Main Results: In total, 8,062 patients qualified for inclusion. Of these, 1,160 patients (14.4%) adopted do-not-resuscitate status after cardiac arrest. We found low rates of survival to hospital discharge among children with do-not-resuscitate status (do-not-resuscitate vs no do-not-resuscitate: 6.0% vs 69.7%). Our study found that rates of do-not-resuscitate status after cardiac arrest are highest in children with Hispanic ethnicity (16.4%), white race (15.0%), and treatment at institutions with larger PICUs (> 50 PICU beds: 17.8%) and at institutions located in North Central (17.6%) and South Atlantic/Puerto Rico (17.1%) regions of the United States. Do-not-resuscitate status was more common among patients with more preexisting conditions, longer duration of cardiac arrest, greater than 1 cardiac arrest, and among patients requiring extracorporeal cardiopulmonary resuscitation. We also found that trends of do-not-resuscitate status after cardiac arrest in children are decreasing in recent years (2013–2015: 13.8%), compared with previous years (2006–2009: 16.0%). Conclusions: Patient-, hospital-, and regional-level factors are associated with do-not-resuscitate status after pediatric cardiac arrest. As cardiac arrest might be a signal of terminal chronic illness, a timely discussion of do-not-resuscitate status after cardiac arrest might help families prioritize quality of end-of-life care. The group authors contributing for the American Heart Association's Get With The Guidelines-Resuscitation Investigators are: Anne-Marie Guerguerian, Elizabeth Foglia, Ericka Fink, Javier J. Lasa, Michael Gaies, Monica Kleinman, Robert Sutton, Taylor L. Sawyer. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Dr. Parshuram disclosed that he is the named inventor of the Bedside Paediatric Early Warning System. The patent is owned by his institution, the Hospital for Sick Children. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: punkaj_gupta@hotmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Risk Factors for Mortality in Critically Ill Children Requiring Renal Replacement Therapy
Objectives: There is an increased mortality risk in critically ill children who require renal replacement therapy for acute kidney injury and fluid overload. Nevertheless, renal replacement therapy is essential in managing these patients. The objective of this study was to identify risk factors for mortality in critically ill children requiring renal replacement therapy. Design: Single-center, retrospective cohort analysis. Setting: Tertiary care children's hospital. Patients: All patients admitted to an ICU at Boston Children's Hospital from January 2009 to December 2017 who required any form of renal replacement therapy. Interventions: None. Measurements and Main Results: Four-hundred sixty-three patients required inpatient renal replacement therapy over the study period. Of these, there were 98 patients who had 99 unique encounters for renal replacement therapy that met eligibility criteria for analysis. The most common diagnoses were respiratory failure, stem cell transplant, and sepsis. The overall mortality was 55.6%. Nonsurvivors had a lower ICU admission weight compared with survivors (30.0 kg vs 44.0 kg; p = 0.037) and a higher degree of fluid accumulation at the time of renal replacement therapy initiation (17.1% vs 8.1%; p = 0.021). In multivariable logistic regression analysis, invasive mechanical ventilation (odds ratio, 7.22; 95% CI, 1.88–27.7), a longer duration of stage 3 acute kidney injury (odds ratio, 1.08; 95% CI, 1.02–1.15), and higher fluid balance in the 72 hours after initiating renal replacement therapy (odds ratio, 1.12; 95% CI, 1.05–1.20) were associated with an increased odds of mortality. Conclusions: Earlier renal replacement therapy initiation with respect to the development of severe acute kidney injury was associated with lower mortality in this cohort of critically ill children. Additionally, invasive mechanical ventilation at the time of renal replacement therapy initiation and a higher degree of fluid accumulation after initiating renal replacement therapy were associated with increased mortality. We confirm that this article has not been published elsewhere and is not under consideration by another journal. All authors have approved the final version of this article and agree with submission to Pediatric Critical Care Medicine. The authors have disclosed that they do not have any potential conflicts of interest. This study was performed at Boston Children's Hospital, Boston, MA. For information regarding this article, E-mail: Daniel.hames@childrens.harvard.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU
Objectives: Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU in the United States. Although individually rare, there are over 6,200 single-gene diseases, which may preclude a genetic diagnosis prior to ICU admission. Rapid whole genome sequencing is an emerging method of diagnosing genetic conditions in time to affect ICU management of neonates; however, its clinical utility has yet to be adequately demonstrated in critically ill children. This study evaluates next-generation sequencing in pediatric critical care. Design: Retrospective cohort study. Setting: Single-center PICU in a tertiary children's hospital. Patients: Children 4 months to 18 years admitted to the PICU who were nominated between July 2016 and May 2018. Interventions: Rapid whole genome sequencing with targeted phenotype-driven analysis was performed on patients and their parents, when parental samples were available. Measurements and Main Results: A molecular diagnosis was made by rapid whole genome sequencing in 17 of 38 children (45%). In four of the 17 patients (24%), the genetic diagnoses led to a change in management while in the PICU, including genome-informed changes in pharmacotherapy and transition to palliative care. Nine of the 17 diagnosed children (53%) had no dysmorphic features or developmental delay. Eighty-two percent of diagnoses affected the clinical management of the patient and/or family after PICU discharge, including avoidance of biopsy, administration of factor replacement, and surveillance for disorder-related sequelae. Conclusions: This study demonstrates a retrospective evaluation for undiagnosed genetic disease in the PICU and clinical utility of rapid whole genome sequencing in a portion of critically ill children. Further studies are needed to identify PICU patients who will benefit from rapid whole genome sequencing early in PICU admission when the underlying etiology is unclear. The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Supported, in part, by grant U19HD077693 from National Institute of Child Health and Human Development and National Human Genome Research Institute. Drs. Sanford's, Briggs's, Watkins's, and Dimmock's institution received funding from Grant U19HD077693 from National Institute of Child Health and Human Development and National Human Genome Research Institute (NHGRI). Drs. Sanford, Clark, Farnaes, Bainbridge, Watkins, Chowdhury, Dimmock, and Kingsmore received support for article research from the National Institutes of Health (NIH). Dr. Sanford also received support for article research from NHGRI. Dr. Briggs disclosed that he is employed by the U.S. Navy. Drs. Bainbridge's and Kingsmore's institutions received funding from the NIH. Dr. Bainbridge disclosed that he is a founder of Codified Genomics LLC. Dr. Dimmock received funding from Biomarin (consultant for Pegvaliase trials), Audentes Therapeutics (Scientific Advisory Board), and Ichorion Therapeutics (consultant for mitochondrial disease drugs). The remaining authors have disclosed that they do not have any potential conflicts of interest. The RCIGM investigators are: Sergey Batalov, Sara Caylor, Katarzyna Ellsworth, Jennifer Friedman, Lisa Salz, Mari Tokita, Kristen Wigby, and Terence Wong. For information regarding this article, E-mail: ncoufal@ucsd.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Factors Impacting Physician Recommendation for Tracheostomy Placement in Pediatric Prolonged Mechanical Ventilation: A Cross-Sectional Survey on Stated Practice
Objectives: To characterize the stated practices of qualified Canadian physicians toward tracheostomy for pediatric prolonged mechanical ventilation and whether subspecialty and comorbid conditions impact attitudes toward tracheostomy. Design: Cross sectional web-based survey. Subjects: Pediatric intensivists, neonatologists, respirologists, and otolaryngology-head and neck surgeons practicing at 16 tertiary academic Canadian pediatric hospitals. Interventions: Respondents answered a survey based on three cases (Case 1: neonate with bronchopulmonary dysplasia; Cases 2 and 3: children 1 and 10 years old with pediatric acute respiratory distress syndrome, respectively) including a series of alterations in relevant clinical variables. Measurements and Main Results: We compared respondents' likelihood of recommending tracheostomy at 3 weeks of mechanical ventilation and evaluated the effects of various clinical changes on physician willingness to recommend tracheostomy and their impact on preferred timing (≤ 3 wk or > 3 wk of mechanical ventilation). Response rate was 165 of 396 (42%). Of those respondents who indicated they had the expertise, 47 of 121 (38.8%), 23 of 93 (24.7%), and 40 of 87 (46.0%) would recommend tracheostomy at less than or equal to 3 weeks of mechanical ventilation for cases 1, 2, and 3, respectively (p < 0.05 Case 2 vs 3). Upper airway obstruction was associated with increased willingness to recommend earlier tracheostomy. Life-limiting condition, severe neurologic injury, unrepaired congenital heart disease, multiple organ system failure, and noninvasive ventilation were associated with a decreased willingness to recommend tracheostomy. Conclusion: This survey provides insight in to the stated practice patterns of Canadian physicians who care for children requiring prolonged mechanical ventilation. Physicians remain reluctant to recommend tracheostomy for children requiring prolonged mechanical ventilation due to lung disease alone at 3 weeks of mechanical ventilation. Prospective studies characterizing actual physician practice toward tracheostomy for pediatric prolonged mechanical ventilation and evaluating the impact of tracheostomy timing on clinically important outcomes are needed as the next step toward harmonizing care delivery for such patients. This work was performed at Children's Hospital of Eastern Ontario/University of Ottawa. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Supported, in part, by a Children's Hospital of Eastern Ontario Research Institute resident research grant. Value: $1,500. Drs. Meyer-Macaulay institution received funding from Children's Hospital of Eastern Ontario Research Institute. Dr. Katz's institution received funding from Canadian Institutes of Health Research, Ontario Thoracic Society, Jesse's Journey, and Muscular Dystrophy Canada, and she received funding from Biogen (speaker's bureau) and Connect Experts (medical expert opinion). Dr. Jouvet's institution received funding from Air Liquide Sante, and he disclosed that Philips and Hamilton Medical lent medical devices. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: cmeyermacaulay@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Acquired von Willebrand Syndrome in Pediatric Extracorporeal Membrane Oxygenation Patients: A Single Institution's Experience
Objectives: 1) Describe the prevalence of acquired von Willebrand syndrome in pediatric patients undergoing extracorporeal membrane oxygenation deemed to be at increased risk for the disease in our institution, 2) discuss the challenges of testing for acquired von Willebrand syndrome diagnosis, 3) describe the characteristics of the patient population found to have acquired von Willebrand syndrome and their outcomes, and 4) discuss the potential implications of acquired von Willebrand syndrome on bleeding complications. Design: Retrospective chart review. Setting: PICU and cardiovascular ICU in a single institution. Patients: All PICU and cardiovascular ICU extracorporeal membrane oxygenation patients 0–18 years old who underwent screening for acquired von Willebrand syndrome between January 2014 and December 2016. Interventions: Humate P administration to a small subset of acquired von Willebrand syndrome positive subjects. Measurements and Main Results: Laboratory data of identified patients were analyzed. The diagnosis of acquired von Willebrand syndrome was made based on decreased ristocetin cofactor activity to von Willebrand factor antigen ratio and/or abnormal multimer analysis. Clinical data were extracted from the chart and through the Pediatric Extracorporeal Membrane Oxygenation Outcome Registry to describe the demographics, comorbidities, and outcomes of this patient population. In the 2 years, 29 patients had laboratory testing performed for surveillance and in cases of clinical bleeding. Of these, 23 (79%) were positive by criteria. No significant difference in mortality rate was found between patients with acquired von Willebrand syndrome versus without. We also did not find a significant difference in the blood product utilization or bleeding complications between patients with acquired von Willebrand syndrome versus without. Humate P was administered in 39% of patients (9/23) who were positive for acquired von Willebrand syndrome, but no significant difference was seen in blood product utilization or bleeding complications between acquired von Willebrand syndrome patients receiving Humate P versus those who did not. Conclusions: Acquired von Willebrand syndrome is a common but under recognized disorder in pediatric extracorporeal membrane oxygenation patients. The clinical implications of this disorder on bleeding and its potential treatments are still unclear. Supported, in part, by grant from the Division of Pediatric Critical Care of Baylor College of Medicine. Dr. Teruya received funding from STAGO, Evaheart, and Octapharma. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at the Texas Children's Hospital. The article falls under nonhuman subject category and was approved by the Baylor College of Medicine Institutional Review Board. For information regarding this article, E-mail: axruth@texaschildrens.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Specific Viral Etiologies Are Associated With Outcomes in Pediatric Acute Respiratory Distress Syndrome
Objectives: Infectious pneumonia is the most common cause of acute respiratory distress syndrome, with viruses frequently implicated as causative. However, the significance of viruses in pediatric acute respiratory distress syndrome is unknown. We aimed to characterize the epidemiology of viral pneumonia in pediatric acute respiratory distress syndrome and compare characteristics and outcomes between pneumonia subjects with and without viruses. Secondarily, we examined the association between specific viruses and outcomes. Design: We performed a secondary analysis of a prospectively enrolled pediatric acute respiratory distress syndrome cohort. Subjects with pneumonia acute respiratory distress syndrome underwent testing of respiratory secretions for viruses and culture for bacteria and fungi and were stratified according to presence or absence of a virus. Setting: Tertiary care children's hospital. Patients: Children with acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Of 544 children with acute respiratory distress syndrome, 282 (52%) had pneumonia as their inciting etiology, of whom 212 were virus-positive. In 141 of 282 (50%) pneumonia acute respiratory distress syndrome cases, a virus was the sole pathogen identified. Virus-positive pneumonia had fewer organ failures but worse oxygenation, relative to virus-negative pneumonia, with no differences in antibiotic use, ventilator duration, or mortality. Subjects with respiratory syncytial virus-associated acute respiratory distress syndrome had lower mortality (0%), and subjects with influenza-associated acute respiratory distress syndrome had shorter ventilator duration, relative to other viral acute respiratory distress syndrome. Nonadeno herpesviruses, tested for exclusively in immunocompromised subjects, had greater than 80% mortality. Conclusions: Pneumonia was the most common cause of pediatric acute respiratory distress syndrome, and viruses were commonly isolated as the sole pathogen. Respiratory syncytial virus and influenza were associated with better outcomes relative to other viral etiologies. Viral pneumonias in immunocompromised subjects, particularly nonadeno herpesviruses, drove the mortality rate for pneumonia acute respiratory distress syndrome. Specific viral etiologies are associated with differential outcomes in pediatric acute respiratory distress syndrome and should be accounted for in future studies. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Dr. Thomas's institution received funding from Gene Fluidics, and he received funding from Therabron and CareFusion. Dr. Yehya's institution received funding from the National Institutes of Health (NIH) (K23-HL136688)/National Heart, Lung, and Blood Institute, and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at Children's Hospital of Philadelphia. For information regarding this article, E-mail: yehyan@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Alexandros Sfakianakis
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