Pediatric Critical Care Medicine

Evaluation of Pediatric Cardiac ICU Advanced Practice Provider Education and Practice Variation Objectives: The education, training, and scope of practice of cardiac ICU advanced practice providers is highly variable. A survey was administered to cardiac ICU advanced practice providers to examine specific variations in orientation format, competency assessment during and at the end of orientation, and scope of clinical practice to determine gaps in resources and need for standardization. Design: This study was a cross-sectional descriptive study utilizing survey responses. Setting: Pediatric cardiac ICUs in the United States. Subjects: The survey was delivered to a convenience sample of advanced practice providers currently practicing in pediatric cardiac ICUs. Interventions: A list of pediatric cardiothoracic surgery programs was generated from the Society of Thoracic Surgery database. A self-administered, electronic survey was delivered via email to advanced practice providers at those institutions. Descriptive data were compared using a chi-square test or Fisher exact test depending on the normalcy of data. Continuous data were compared using a Student t test or Mann-Whitney U test. Measurements and Main Results: Eighty-three of 157 advanced practice providers responded (53% response rate, representing 36 institutions [35% of institutions]). Sixty-five percent of respondents started as new graduates. Ninety-three to one-hundred percent obtain a history and physical, order/interpret laboratory, develop management plans, order/titrate medications, and respiratory support. Ability to perform invasive procedures was highly variable but more likely for those in a dedicated cardiac ICU. Seventy-seven percent were oriented by another advanced practice provider, with a duration of orientation less than 4 months (66%). Fifty percent of advanced practice providers had no guidelines in place to guide learning/competency during orientation. Sixty-seven percent were not evaluated in any way on their knowledge or skills during or at the end of orientation. Orientation was rated as poor/fair by the majority of respondents for electrophysiology (58%) and echocardiography (69%). Seventy-one percent rated orientation as moderately effective or less. Respondents stated they would benefit from more structured didactic education with clear objectives, standardized management guidelines, and more simulation/procedural practice. Eighty-five percent were very/extremely supportive of a standardized cardiac ICU advanced practice provider curriculum. Conclusions: Orientation for cardiac ICU advanced practice providers is highly variable, content depends on the institution/preceptor, and competency is not objectively defined or measured. A cardiac ICU advanced practice provider curriculum is needed to standardize education and promote the highest level of advanced practice provider practice. 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. Address requests for reprints to: Lindsey Justice, DNP, APRN, CPNP-AC, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229. E-mail: Lindsey.Justice@cchmc.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Extracorporeal Membrane Oxygenation for Severe Adenoviral Pneumonia in Neonatal, Pediatric, and Adult Patients Objectives: We examined data on patients with severe adenoviral pneumonia from the international registry of the Extracorporeal Life Support Organization to identify risk factors for mortality in patients receiving extracorporeal membrane oxygenation. Design: Retrospective analysis. Setting: International Registry of Extracorporeal Life Support Organization. Patients: We collected de-identified data on all patients with adenoviral pneumonia who needed extracorporeal membrane oxygenation from 1992 to 2016 using International Classification of Diseases, 9th Edition, criteria. Interventions: Our primary outcome measure was in-hospital mortality. We also collected data on demographics, preextracorporeal membrane oxygenation ventilator settings, biochemical variables, extracorporeal membrane oxygenation mode, duration, and complications. Initial bivariate analysis assessed potential associations between mortality and various preextracorporeal membrane oxygenation variables as well as extracorporeal membrane oxygenation factors. Variables with p values of less than 0.1 were considered for logistic regression analysis that identified predictors of mortality. Measurements and Results: There were 542 patients with adenoviral pneumonia who were supported with extracorporeal membrane oxygenation. Overall mortality was 58% (307/529 patients) (neonates 86.4% [108/125 patients], children 49% [158/327 patients], and adults 49% [41/83 patients]). Multivariate regression identified hypercapnia (PCO2 > 45.7; odds ratio > 3.2; p < 0.001), immunosuppression (odds ratio, 4.44; 95% CI, 1.69–11.61; p = 0.002] and lack of pharmacologic paralysis (odds ratio, 0.30; 95% CI, 0.16–0.57; p < 0.001] as significant preextracorporeal membrane oxygenation factors for mortality. Neonatal patients had significantly higher mortality than pediatric or adult patients (odds ratio, 10.9; 95% CI, 3.2–37.3; p < 0.001). The presence of renal (odds ratio, 4.4; 95% CI, 2.5–7.7; p < 0.001), neurologic (odds ratio, 2.5; 95% CI, 1.2–5.1; p = 0.014), hemorrhagic (odds ratio, 2.2; 95% CI, 1.2–4.0; p = 0.014), or cardiovascular complications (odds ratio, 2.4; 95% CI, 1.3–4.6; p = 0.006) was associated with higher mortality on extracorporeal membrane oxygenation. Conclusions: Patients with adenoviral pneumonia supported on extracorporeal membrane oxygenation had mortality of 58% over a 25-year-old period. We identified risk factors both before and during extracorporeal membrane oxygenation which were associated with higher mortality. Mortality in neonatal patients was particularly high. 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. This work was performed at Cardiothoracic ICU, National University Heart Centre, Singapore. For information regarding this article, E-mail: ram_ramanathan@nuhs.edu.sg ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

The Effect of Levosimendan Versus Milrinone on the Occurrence Rate of Acute Kidney Injury Following Congenital Heart Surgery in Infants: A Randomized Clinical Trial Objectives: It has been shown that, in contrast to other inotropic agents, levosimendan improves glomerular filtration rate after adult cardiac surgery. The aim of this study was to investigate the efficacy of levosimendan, compared with milrinone, in preventing acute kidney dysfunction in infants after open-heart surgery with cardiopulmonary bypass. Design: Two-center, double-blinded, prospective, randomized clinical trial. Setting: The study was performed in two tertiary pediatric centers, one in Sweden (Gothenburg) and one in Finland (Helsinki). Patients: Infants between 1 and 12 months old, diagnosed with Tetralogy of Fallot, complete atrioventricular septal defect or nonrestrictive ventricular septal defect, undergoing total corrective cardiac surgery with cardiopulmonary bypass. Interventions: Seventy-two infants were randomized to receive a perioperative infusion of levosimendan (0.1 µg/kg/min) or milrinone (0.4 µg/kg/min). The infusion was initiated at the start of cardiopulmonary bypass and continued for 26 hours. Measurements and Main Results: The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1. Secondary outcomes included the following: 1) acute kidney injury according to the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes; 2) acute kidney injury with serum creatinine corrected for fluid balance; 3) plasma neutrophil gelatinase-associated lipocalin; 4) cystatin C; 5) urea; 6) lactate; 7) hemodynamic variables; 8) use of diuretics in the PICU; 9) need of dialysis; 10) length of ventilator therapy; and 11) length of PICU stays. There was no significant difference in postoperative serum creatinine between the treatment groups over time (p = 0.65). The occurrence rate of acute kidney injury within 48 hours was 46.9% in the levosimendan group and 39.5% in the milrinone group (p = 0.70). There were no significant differences in other secondary outcome variables between the groups. Conclusions: Levosimendan compared with milrinone did not reduce the occurrence rate of acute kidney injury in infants after total corrective heart surgery for atrioventricular septal defect, ventricular septal defect, or Tetralogy of Fallot. † Deceased January 9, 2018. Drs. Thorlacius and Castellheim received support for article research from European Society of Anesthesiology, Scandinavian Society of Anesthesiology and Intensive Care Medicine, The Gothenburg Society of Medicine, Queen Silvia's Jubilee Fund, Swedish Society for Anesthesiology and Intensive Care, The Samariten foundation for pediatric research, and funds under the ALF agreement (the Swedish governmental funds for research and education). Drs. Thorlacius, Suominen, Wåhlander, Vistnes, and Castellheim disclosed off-label product use of levosimendan as an inodilator, which is off-label for pediatric patients in Finland and Sweden. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: elin.thorlacius@gu.se ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Matched Retrospective Cohort Study of Thiamine to Treat Persistent Hyperlactatemia in Pediatric Septic Shock Objectives: Thiamine deficiency may propagate lactate production by limiting pyruvate dehydrogenase activity, and studies suggest benefit for thiamine administration in septic adults. We studied the effect of thiamine on physiologic and clinical outcomes for children with septic shock and hyperlactatemia. Design: Retrospective matched cohort study. Setting: Single academic PICU. Patients: Six thiamine-treated cases and nine matched controls. Interventions: None. Measurements and Main Results: The primary outcome was change in blood lactate from prethiamine (T0, cases) or maximum (T0, controls) lactate through 24 hours later (T24). Secondary outcomes were change in lactate over 48 hours (T48) and 72 hours (T72), time to lactate normalization, changes in vasoactive-inotrope score, organ dysfunction severity (daily Pediatric Logistic Organ Dysfunction 2 score), and creatinine, PICU length of stay, and hospital mortality. Lactate was greater than 5 mmol/L for a median of 39 hours (range, 16.1–64.3 hr) prior to thiamine administration for cases compared with 3.4 hours (range, 0–22.9 hr) prior to maximum lactate for controls (p = 0.002). There was no difference in median (interquartile range) change in lactate from T0 to T24 between thiamine-treated cases and controls (–9.0, –17.0 to -5.0 vs –7.2, –9.0 to –5.3 mmol/L, p = 0.78), with both groups exhibiting a rapid decrease in lactate. There were also no differences in secondary outcomes between groups. Conclusions: Treatment of pediatric septic shock with thiamine was followed by rapid improvement in physiologic and clinical outcomes after prolonged hyperlactatemia. Although we are not able to infer that thiamine provided benefit over usual care, the rapid decline in lactate after thiamine despite a prolonged period of hyperlactatemia raises the possibility that thiamine helped to reverse lactate production. Supported, in part, by grant from the National Institute of General Medical Sciences K23GM110496 (to Dr. Weiss) and the Department of Anesthesiology and Critical Care at the Children's Hospital of Philadelphia. Drs. Weiss's and Blowey's institutions received funding from National Institute of General Medical Sciences K23GM110496. Drs. Weiss, Blowey, and Ganetzky received support for article research from the National Institutes of Health (NIH). Dr. Ganetzky received funding from the NIH. Dr. Sutton's institution received funding from NIH National Heart, Lung, and Blood Institute R01; he received funding from Zoll Medical (speaking honoraria); and he disclosed he is a writing group member of the Pediatric Advanced Life Support Guidelines and Chair of the American Heart Association's Get With the Guidelines-Resuscitation Pediatric Research Task Force. The remaining authors have disclosed that they do not have any potential conflicts of interest. This study was performed at the Children's Hospital of Philadelphia. Address requests for reprints to: Scott L. Weiss, MD, MSCE, FCCM, Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 3401 Civic Center Blvd, Wood Building 6th Floor, Suite 6026A, Philadelphia, PA 19104. E-mail: WeissS@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Strengths and Difficulties Questionnaire Assessment of Long-Term Psychological Outcome in Children After Intensive Care Admission Objectives: We investigated the long-term psychologic symptoms of patients who survived pediatric intensive care admission. Design: Longitudinal follow-up study. Setting: Nationwide cohort study based on a national ICU register and a questionnaire survey. Patients: All pediatric patients (0–16 yr old) who were admitted to an ICU in Finland in 2009–2010. Interventions: None. Measurements and Main Results: Six years after ICU admission, all surviving patients were sent the Strengths and Difficulties Questionnaire, and questionnaires regarding chronic diseases and need for medication and therapy. At the end of the follow-up period, there were 3,674 surviving children who had been admitted to an ICU in 2009–2010. Of these children, 1,105 completed the Strengths and Difficulties Questionnaire 6 years after admission. Strengths and Difficulties Questionnaire scores were abnormal for 84 children (7.6%), borderline for 80 (7.2%), and normal for 941 (85.2%). Participants with abnormal scores were younger at admission to the ICU (3.06 vs 4.70 yr; p = 0.02), and more commonly had a chronic disease (79.5% vs 47.4%; p < 0.001), a need for continuous medication (49.4% vs 31.7%; p < 0.001), a need for therapy (58.5% vs 15.9%; p < 0.001), and a need for annual healthcare visits (91.4% vs 85.2%; p = 0.05). Abnormal Strengths and Difficulties Questionnaire scores were associated with higher rates of neurologic (32.1% vs 10.2%), gastrointestinal (7.1% vs 3.9%), psychiatric (3.6% vs 0.5%), and chromosomal disorders (9.5% vs 1.3%), as well as with long-term pain (1.2% vs 0.6%). Conclusions: Participants with abnormal Strengths and Difficulties Questionnaire scores (poor psychologic outcome) at 6 years after childhood ICU admission more commonly suffered neurologic, chromosomal, or psychiatric diagnoses or long-term pain, and generally required higher levels of healthcare services, therapies, and medication. Dr. Kyösti received support for article research from Alma and K. A. Snellman Foundation Finnish grant for Pediatric Research. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: elina.kyosti@ppshp.fi ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Innovation in Central Venous Access Device Security: A Pilot Randomized Controlled Trial in Pediatric Critical Care Objectives: Central venous access devices enable many treatments during critical illness; however, 25% of pediatric central venous access devices fail before completion of treatment due to infection, thrombosis, dislodgement, and occlusion. This is frequently attributed to inadequate securement and dressing of the device; however, high-quality research evaluating pediatric central venous access device securement innovation to prevent central venous access device failure is scarce. This study aimed to establish the feasibility of a definitive randomized control trial examining the effectiveness of current and new technologies to secure central venous access devices in pediatrics. Design: Single-center, parallel group, superiority, pilot randomized control trial. Setting: Anesthetic and intensive care departments of a tertiary pediatric hospital Subjects: One-hundred eighty pediatric patients with nontunneled central venous access device Interventions: Participants were randomized to receive central venous access device securement via standard care (bordered polyurethane dressing, with prolene sutures, chlorhexidine gluconate disc), tissue adhesive (Histoacryl, B Braun, Melsungen, Germany) in addition to standard care; or integrated dressing securement (SorbaView SHIELD [Centurion Medical Products, Franklin, MA], with prolene sutures and chlorhexidine gluconate disc). Outcomes: Primary: Feasibility (including effect size estimates, acceptability); central venous access device failure; central venous access device complications; secondary: individual central venous access device complications, skin damage, dressing performance, and product cost. Measurements and Main Results: Feasibility criteria were achieved as recruitment occurred with acceptable eligibility, recruitment, missing data, and attrition rates, as well as good protocol adherence. Family members and staff-reported comparable levels of acceptability between study arms; however, tissue adhesive was reported as the most difficult to apply. Overall, 6% of central venous access devices failed, including 6% (3/54; incident rate, 13.2 per 1,000 catheter days) standard care, 2% (1/56; incident rate, 3.65 per 1,000 catheter days) integrated, and 8% (5/59; 25.0 per 1,000 catheter days) tissue adhesive. Conclusions: It is feasible to conduct an efficacy randomized control trial of the studied interventions. Further research is required to definitively identify clinical, cost-effective methods to prevent central venous access device failure by examining new dressing and securement technologies and techniques. 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. Ullman's institution has received an unrestricted research grant from Centurion Medical Products (dressing manufacturers) to support research, 3M (dressing manufacturers) to support research, Becton Dickinson (dressing manufacturers) to support research. Drs. Ullman and Rickards' institutions received investigator-initiated grants, or consultancy payments on behalf of Ms. Rickard from vascular access product manufacturers (3M, Adhezion, Angiodynamics, Bard, Baxter, Becton Dickinson, BBraun, Centurion Medical Products, Entrotech, Medtronic, and Smiths Medical). Dr. Long's institution received funding from Griffith University (payment for recruitment and data entry). The remaining authors have disclosed that they do not have any potential conflicts of interest. Clinical trial registration: ACTRN12615000977572. For information regarding this article, E-mail: a.ullman@griffith.edu.au ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Bleeding and Thrombosis With Pediatric Extracorporeal Life Support: A Roadmap for Management, Research, and the Future From the Pediatric Cardiac Intensive Care Society (Part 1) Objectives: To make practical and evidence-based recommendations on improving understanding of bleeding and thrombosis with pediatric extracorporeal life support and to make recommendations for research directions. Data Sources: Evaluation of literature and consensus conferences of pediatric critical care and extracorporeal life support experts. Study Selection: A team of 10 experts with pediatric cardiac and extracorporeal membrane oxygenation experience and expertise met through the Pediatric Cardiac Intensive Care Society to review current knowledge and make recommendations for future research to establish "best practice" for anticoagulation management related to extracorporeal life support. Data Extraction/Synthesis: The first of a two-part white article focuses on clinical understanding and limitations of medications in use for anticoagulation, including novel medications. For each medication, limitations of current knowledge are addressed and research recommendations are suggested to allow for more definitive clinical guidelines in the future. Conclusions: No consensus on best practice for anticoagulation exists. Structured scientific evaluation to answer questions regarding anticoagulant medication and bleeding and thrombotic events should occur in multicenter studies using standardized approaches and well-defined endpoints. Outcomes related to need for component change, blood product administration, healthcare outcome, and economic assessment should be incorporated into studies. All centers should report data on patients receiving extracorporeal life support to a registry. The Extracorporeal Life Support Organization registry, designed primarily for quality improvement purposes, remains the primary and most successful data repository to date. Drs. Penk and Reddy contributed equally as first coauthors. The work for this project occurred during monthly phone meetings and at each of the institutions listed above for the authors. Dr. Reddy's institution received funding from the National Institutes of Health and the American Heart Association. Dr. Thiagarajan's institution received funding from Bristol Myers Squibb and Pfizer. Dr. Dalton received funding from Innovative ECMO Concepts (consultant), and she disclosed off-label product use of extracorporeal membrane oxygenation. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jamiepenk@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Severity and Mortality Predictors of Pediatric Acute Respiratory Distress Syndrome According to the Pediatric Acute Lung Injury Consensus Conference Definition Objectives: The objective of this study was to assess the prevalence, severity, and outcomes of pediatric acute respiratory distress syndrome in a resource-limited country. In addition, we sought to explore the predisposing factors that predicted the initial severity, a change from mild to moderate-severe severity, and mortality. Design: Retrospective study. Setting: PICU in Songklanagarind Hospital, Songkhla, Thailand. Patients: Children 1 month to 15 years old with acute respiratory failure admitted to the PICU from January 2013 to December 2016. Interventions: None. Measurements and Main Results: From a total of 1,738 patients admitted to PICU, 129 patients (prevalence 7.4%) were diagnosed as pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference definition. The patients were categorized by severity. Fifty-seven patients (44.2%) were mild, 35 (27.1%) were moderate, and 37 (28.1%) were severe. After multivariable analysis was performed, factors significantly associated with moderate to severe disease at the initial diagnosis were Pediatric Risk of Mortality III score (odds ratio, 1.08; 95% CI, 1.03–1.15; p = 0.004), underlying oncologic/hematologic disorder (odds ratio, 0.32; 95% CI, 0.12–0.77; p = 0.012), and serum albumin level (odds ratio, 0.46; 95% CI, 0.27–0.80; p = 0.006), whereas underlying oncologic/hematologic disorder (odds ratio, 5.33; 95% CI, 1.33–21.4) and hemoglobin (odds ratio, 0.63; 95% CI, 0.44–0.89) predicted the progression of this syndrome within 7 days. The 30-day all-cause mortality rate was 51.2% (66/129). The predictors of mortality were the Pediatric Risk of Mortality III score (odds ratio, 1.12; 95% CI, 1.02–1.24; p = 0.017), underlying oncologic/hematologic disorder (odds ratio, 7.81; 95% CI, 2.18–27.94; p = 0.002), receiving systemic steroids (odds ratio, 4.04; 95% CI, 1.25–13.03; p = 0.019), having air leak syndrome (odds ratio, 5.45; 95% CI, 1.57–18.96; p = 0.008), and presenting with multiple organ dysfunction (odds ratio, 7.41; 95% CI, 2.00–27.36; p = 0.003). Conclusions: The prevalence and mortality rate of pediatric acute respiratory distress syndrome in a developing country are high. The oncologic/hematologic comorbidity had a significant impact on the severity of progression and mortality. 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 from the Faculty of Medicine, Prince of Songkla University Research Funding. The author(s) have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: pharsai_16@yahoo.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Antipyretic Efficacy of Acetaminophen and Ibuprofen in Critically Ill Pediatric Patients Objectives: To determine the antipyretic efficacy of acetaminophen (IV, enteral, rectal) and ibuprofen (enteral) in critically ill febrile pediatric patients. Design: Retrospective cohort study. Setting: Quaternary care pediatric hospital ICUs. Patients: Pediatric patients less than 19 years old who were febrile (≥ 38.0°C), received a dose of IV acetaminophen, enteral acetaminophen, rectal acetaminophen, or enteral ibuprofen and had at least one temperature measurement in the following 6 hours. Interventions: None. Measurements and Main Results: A total of 3,341 patients (55.8% male, median age 2.5 yr [interquartile range, 0.63–9.2 yr]) met study criteria. Baseline temperature was median 38.6°C (interquartile range, 38.3–38.9°C) measured via axillary (76.9%) route. Patients became afebrile (87.5%) at median 1.4 hours (interquartile range, 0.77–2.3 hr) after the first dose of medication, a –2.9 ± 1.6% change in temperature. Antipyretic medications included as follows: enteral acetaminophen (n = 1,664), IV acetaminophen (n = 682), rectal acetaminophen (n = 637), and enteral ibuprofen (n = 358). Enteral ibuprofen had a significantly greater odds of defervescence on multivariable logistic regression analysis (p = 0.04) with a decrease of –1.97 ± 0.89°C while IV acetaminophen was significant for a decreased time to defervescence at median 1.5 hours (interquartile range 0.8–2.3 hr) after a dose (p = 0.03). Patient age, presence of obesity, and baseline temperature were significant for decreased antipyretic efficacy (p < 0.05). Conclusions: Enteral ibuprofen was the most efficacious antipyretic and IV acetaminophen had the shortest time to defervescence. Dr. Moffett disclosed off-label product use of IV acetaminophen for antipyresis in children. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: bsmoffet@texaschildrens.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Mortality and Factors Associated With Hemorrhage During Pediatric Extracorporeal Membrane Oxygenation Objectives: To quantify and identify factors associated with bleeding events during pediatric extracorporeal membrane oxygenation. Design: Retrospective cohort study with primary outcome of bleeding days on extracorporeal membrane oxygenation. Setting: Single tertiary care children's hospital. Subjects: One-hundred twenty-two children supported with extracorporeal membrane oxygenation for greater than 12 hours during January 2015 through December 2016. Interventions: Bleeding days were identified if mediastinal or cannula site exploration, activated factor VII administration, gastrointestinal, pulmonary, or intracranial hemorrhages occurred. Logistic regression was used to assess factors associated with bleeding days. Measurements and Main Results: Study population was identified from institutional extracorporeal membrane oxygenation database. Clinical, laboratory, and survival data were obtained from medical records. Only data from patients' first extracorporeal membrane oxygenation run were used. One-hundred twenty-two patients with median age of 17 weeks (interquartile range, 1–148 wk) were analyzed. Congenital heart disease (n = 56, 46%) was the most common diagnosis. Bleeding days comprised 179 (16%) of the 1,121 observed extracorporeal membrane oxygenation-patient-days. By extracorporeal membrane oxygenation day 4, 50% of users had experienced a bleeding day. Central rather than peripheral cannulation (odds ratio, 2.58; 95% CI, 1.47–4.52; p < 0.001), older age (odds ratio, 1.31 per increased week; 95% CI, 1.14–1.52; p < 0.001), higher lactate (odds ratio, 1.08 per 1 mmol/L increase; 95% CI, 1.05–1.12; p < 0.001), and lower platelets (odds ratio, 0.87 per 25,000 cell/μL increase; 95% CI, 0.77–0.99; p = 0.005) were associated with bleeding days. Patients who experienced more frequent bleeding (> 75th percentile) had fewer ventilator-free and hospital-free days in the 60 days after cannulation (0 vs 31; p = 0.002 and 0 vs 0; p = 0.008) and higher in-hospital mortality (68 vs 34%; p < 0.001). Conclusions: Central cannulation, older age, low platelets, and high lactate are associated with bleeding days during pediatric extracorporeal membrane oxygenation. Patients who bleed more frequently during extracorporeal membrane oxygenation have higher in-hospital mortality, longer technological dependence, and reduced hospital-free days. This study was performed at Boston Children's Hospital, Boston, MA. Supported, in part, by grant from the Callahan Family Chair Fund. Dr. Thiagarajan's institution received funding from Bristol Myers Squibb and Pfizer. Dr. Alexander's institution received funding from Novartis and Tenax Therapeutics (supply therapeutic agent, levosimendan, only as part of an Expanded Access clinical trial). Dr. Alexander's institution received consultation fees from Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: conor.ohalloran@childrens.harvard.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
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6948891480

alsfakia@gmail.com