Outcomes After Respiratory Extracorporeal Life Support in Teens and Young Adults: An Extracorporeal Life Support Organization Registry Analysis.

OBJECTIVES: A recent study from Germany found that survival after respiratory extracorporeal life support (ECLS) was lower among patients 10-20 years old than 20-30 years old. The objective of this study was to compare survival between teenage and young adult patients who receive respiratory ECLS. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization registry, an international prospective quality improvement database. PATIENTS: All patients ages 16-30 years cannulated for respiratory indications from 1990 to 2020 were included. Patients were divided into two groups, teens (16-19 yr old) and young adults (20-30 yr old). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was survival to discharge. Variables were considered for the multivariate logistic regression model if there was both a statistically significant difference (p ≤ 0.05) and a clinically meaningful absolute difference between the groups. A total of 5,751 patients were included, of whom 1,653 (29%) were teens and 4,098 (71%) were young adults. Survival to discharge was higher in young adults than teens, 69% versus 63% (p < 0.001). Severity of illness was higher among teens; however, survival within each stratum defined by Pao2/Fio2 ratio was higher in young adults than in teens. Use of venoarterial ECLS was higher in teens than in young adults, 15% versus 7%, respectively. Teens were more likely to receive high-frequency oscillatory ventilation and this therapy was associated with a longer time from admission to ECLS initiation. After adjusting for variables that differ significantly between the groups, the odds ratio for survival in young adults compared with teens was 1.14 (95% CI, 1.004-1.3). CONCLUSIONS: In this large multicenter retrospective study, mortality was higher in teens than in young adults who received respiratory ECLS. This difference persisted after adjusting for multiple variables and the mechanism underlying these findings remains unclear.

Pediatric Hematology and Oncology Patients on Extracorporeal Membrane Oxygenation: Outcomes in a Multicenter, Retrospective Cohort, 2009-2021.

OBJECTIVE: To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Multicenter, retrospective study. SETTING: Sixteen PICUs in the United States and Israel. PATIENTS: We included patients aged younger than 19 years with an oncologic diagnosis or HCT who required ECMO support between 2009 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 149 patients were included in the study cohort. There were 118 patients with an oncologic diagnosis and 31 that received HCT. The indications for ECMO were respiratory failure (46%), combined respiratory and cardiac failure (28%), and cardiac failure (25%). Venovenous (V-V) ECMO was used in 45% of patients, with 53% of patients being placed on venoarterial (V-A) ECMO. For oncologic and HCT groups, survival to ECMO decannulation was 52% (62/118) and 64% (20/31), and survival to hospital discharge was 36% (43/118) and 42% (13/31), respectively. After adjusting for other factors, requiring cardiopulmonary resuscitation was associated with greater odds ratio of mortality (3.0 [95% CI, 1.2-7.7]). CONCLUSIONS: Survival to ECMO decannulation of pediatric oncologic and HCT patients in this study was 52-64%, depending upon diagnosis. However, survival to hospital discharge remains poor. Future research should prioritize understanding factors contributing to this survival gap within these patient populations.

Management of Pediatric Pneumonia: A Decade After the Pediatric Infectious Diseases Society and Infectious Diseases Society of America Guideline.

BACKGROUND: Incomplete uptake of guidelines can lead to nonstandardized care, increased expenditures, and adverse clinical outcomes. The objective of this study was to evaluate the impact of the 2011 Pediatric Infectious Diseases Society and Infectious Diseases Society of America (PIDS/IDSA) pediatric community-acquired pneumonia (CAP) guideline that emphasized aminopenicillin use and de-emphasized the use of chest radiographs (CXRs) in certain populations. METHODS: This quasi-experimental study queried a national administrative database of children's hospitals to identify children aged 3 months-18 years with CAP who visited 1 of 28 participating hospitals from 2009 to 2021. PIDS/IDSA pediatric CAP guideline recommendations regarding antibiotic therapy, diagnostic testing, and imaging were evaluated. Segmented regression interrupted time series was used to measure guideline-concordant practices with interruptions for guideline publication and the Coronavirus Disease 2019 (COVID-19) pandemic. RESULTS: Of 315 384 children with CAP, 71 804 (22.8%) were hospitalized. Among hospitalized children, there was a decrease in blood culture performance (0.5% per quarter) and increase in aminopenicillin prescribing (1.1% per quarter). Among children discharged from the emergency department (ED), there was an increase in aminopenicillin prescription (0.45% per quarter), whereas the rate of obtaining CXRs declined (0.12% per quarter). However, use of CXRs rebounded during the COVID-19 pandemic (increase of 1.56% per quarter). Hospital length of stay, ED revisit rates, and hospital readmission rates remained stable. CONCLUSIONS: Guideline publication was associated with an increase of aminopenicillin prescribing. However, rates of diagnostic testing did not materially change, suggesting the need to consider implementation strategies to meaningfully change clinical practice for children with CAP.

The Use of Extracorporeal Life Support in Children With Immune-Mediated Diseases.

OBJECTIVES: To describe the use and outcomes of extracorporeal membrane oxygenation support among children with immune-mediated conditions. DESIGN: Retrospective cohort study. SETTING: The Extracorporeal Life Support Organization registry. PATIENTS: Patients 1 month to 18 years old with International Classification of Diseases, 9th Edition and International Classification of Diseases, 10th Edition codes for immune-mediated conditions from 1989 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 207 patients with an immune-mediated condition received extracorporeal membrane oxygenation, and 50% survived to discharge. Most patients (63%) received extracorporeal membrane oxygenation for respiratory support with 53% survival, 21% received cardiac support (55% survival), and 15% received extracorporeal cardiopulmonary resuscitation (34% survival). The most common diagnosis among nonsurvivors was hemophagocytic lymphohistiocytosis/macrophage activation syndrome with 37% survival. Patients with juvenile idiopathic arthritis (23%) and dermatomyositis (25%) had the lowest survival. Nonsurvivors had a higher frequency of infections, neurologic complications, and renal replacement therapy use. Use of preextracorporeal membrane oxygenation corticosteroids was associated with mortality. CONCLUSIONS: Children with immune-mediated conditions can be successfully supported with extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation use has increased over time, and survival varies considerably by diagnosis.

Antibiotic Choice and Clinical Outcomes in Ambulatory Children with Community-Acquired Pneumonia.

OBJECTIVES: To describe antibiotic prescribing patterns in ambulatory children with community-acquired pneumonia and to assess the relationship between antibiotic selection and clinical outcomes. STUDY DESIGN: This was a retrospective cohort study of ambulatory Medicaid-enrolled children 0-18 years of age diagnosed with community-acquired pneumonia from 2010 to 2016. The exposure was antibiotic class: narrow-spectrum (aminopenicillins), broad-spectrum (amoxicillin/clavulanate and cephalosporins), macrolide monotherapy, macrolides with narrow-spectrum antibiotics, or macrolides with broad-spectrum antibiotics. The associations between antibiotic selection and the outcomes of subsequent hospitalization and development of severe pneumonia (chest drainage procedure, intensive care admission, mechanical ventilation) were assessed, controlling for measures of illness severity. RESULTS: Among 252 177 outpatient pneumonia visits, macrolide monotherapy was used in 43.2%, narrow-spectrum antibiotics in 26.1%, and broad-spectrum antibiotics in 24.7%. A total of 1488 children (0.59%) were subsequently hospitalized and 117 (0.05%) developed severe pneumonia. Compared with children receiving narrow-spectrum antibiotics, the odds of subsequent hospitalization were higher in children receiving broad-spectrum antibiotics (aOR, 1.34; 95% CI, 1.17-1.52) and lower in children receiving macrolide monotherapy (aOR, 0.64; 95% CI, 0.55-0.73) and macrolides with narrow-spectrum antibiotics (aOR, 0.62; 95% CI, 0.39-0.97). Children receiving macrolide monotherapy had lower odds of developing severe pneumonia than children receiving narrow-spectrum antibiotics (aOR, 0.56; 95% CI, 0.33-0.93). However, the absolute risk difference was <0.5% for all analyses. CONCLUSIONS: Macrolides are the most commonly prescribed antibiotic for ambulatory children with community-acquired pneumonia. Subsequent hospitalization and severe pneumonia are rare. Future efforts should focus on reducing broad-spectrum and macrolide antibiotic prescribing.

Short- Versus Prolonged-Duration Antibiotics for Outpatient Pneumonia in Children.

OBJECTIVE: To identify practice patterns in the duration of prescribed antibiotics for the treatment of ambulatory children with community-acquired pneumonia (CAP) and to compare the frequency of adverse clinical outcomes between children prescribed short-vs prolonged-duration antibiotics. STUDY DESIGN: We performed a retrospective cohort study from 2010-2016 using the IBM Watson MarketScan Medicaid Database, a claims database of publicly insured patients from 11 states. We included children 1-18 years old with outpatient CAP who filled a prescription for oral antibiotics (n = 121 846 encounters). We used multivariable logistic regression to determine associations between the duration of prescribed antibiotics (5-9 days vs 10-14 days) and subsequent hospitalizations, new antibiotic prescriptions, and acute care visits. Outcomes were measured during the 14 days following the end of the dispensed antibiotic course. RESULTS: The most commonly prescribed duration of antibiotics was 10 days (82.8% of prescriptions), and 10.5% of patients received short-duration therapy. During the follow-up period, 0.2% of patients were hospitalized, 6.2% filled a new antibiotic prescription, and 5.1% had an acute care visit. Compared with the prolonged-duration group, the aORs for hospitalization, new antibiotic prescriptions, and acute care visits in the short-duration group were 1.16 (95% CI 0.80-1.66), 0.93 (95% CI 0.85-1.01), and 1.06 (95% CI 0.98-1.15), respectively. CONCLUSIONS: Most children treated for CAP as outpatients are prescribed at least 10 days of antibiotic therapy. Among pediatric outpatients with CAP, no significant differences were found in rates of adverse clinical outcomes between patients prescribed short-vs prolonged-duration antibiotics.

Conversion From Activated Clotting Time to Anti-Xa Heparin Activity Assay for Heparin Monitoring During Extracorporeal Membrane Oxygenation.

OBJECTIVES: Anticoagulation with unfractionated heparin remains the most common therapy used to prevent circuit thrombosis during extracorporeal membrane oxygenation, but no consensus exists on the optimal method or targets for heparin monitoring. From 2015 to 2018, we switched from monitoring heparin during extracorporeal membrane oxygenation using activated clotting times to anti-Xa heparin activity assays. This study describes the transition from activated clotting time to anti-Xa heparin activity assay monitoring and the associated clinical changes. DESIGN: Retrospective analysis at single institution. SETTING: Referral Children's Hospital. PATIENTS: A total of 145 pediatric patients over 152 extracorporeal membrane oxygenation runs using 206 extracorporeal membrane oxygenation circuits. INTERVENTIONS: Anticoagulation protocol quality improvement. MEASUREMENTS AND MAIN RESULTS: From 2015 to 2018, heparin monitoring during extracorporeal membrane oxygenation changed from hourly activated clotting time to anti-Xa heparin activity assay every 6 hours with an associated 75% reduction in the circuit changes per extracorporeal membrane oxygenation day. Over the 4 years, patients with an average anti-Xa heparin activity assay of at least 0.25 U/mL showed a 59% reduction in circuit changes per extracorporeal membrane oxygenation day compared with less than 0.15 U/mL. In addition to its association with reduced circuit changes, anti-Xa heparin activity assay monitoring was also associated with reduced heparin dose changes per day from 11 ± 4 to 2 ± 1 (p < 0.001), smaller heparin dose changes (less variation in dose), and reduced diagnostic phlebotomy volumes from 41 ± 6 to 25 ± 11 mL/day (p < 0.001). The number of patients with reported bleeding decreased from 69% using activated clotting time to 51% (p = 0.03). Transfusion rates did not change. CONCLUSIONS: Over 4 years, we replaced the activated clotting time assay with the anti-Xa heparin activity assay for heparin monitoring during extracorporeal membrane oxygenation. Minimum anti-Xa heparin activity assay levels of 0.25 U/mL were associated with reduced circuit changes. Further studies are needed to determine the optimum anti-Xa heparin activity assay therapeutic range during extracorporeal membrane oxygenation.

Outcomes After In-Hospital Pediatric Recurrent Cardiac Arrests.

OBJECTIVES: The objective of this study is to determine outcomes of recurrent cardiac arrest events in the general pediatric inpatient population. DESIGN: Retrospective cohort study of inpatients in a single institution. SETTING: A tertiary care free-standing children's hospital. PATIENTS: All patients less than 18 years old at Seattle Children's Hospital with recurrent cardiac arrest events occurring from January 1, 2010, to March 1, 2018, were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall survival to hospital discharge was 50% and all survivors had a good neurologic outcome, defined as Pediatric Cerebral Performance Category of 3 or less, or unchanged from baseline. Survival among patients who received extracorporeal life support was 43% and among those who received extracorporeal cardiopulmonary resuscitation, 33%. Initial arrest factors associated with survival included initial rhythm of ventricular tachycardia or ventricular fibrillation, shorter duration of cardiopulmonary resuscitation, and absence of multiple organ dysfunction. Additionally, nonsurvivors had more severe metabolic acidosis in the prearrest and postarrest period. CONCLUSIONS: Survival after pediatric in-hospital recurrent cardiac arrest is higher than previously reported. There is also evidence that initial rhythm other than ventricular tachycardia/ventricular fibrillation and longer duration of cardiopulmonary resuscitation as well as multiple organ dysfunction and more severe lactic acidosis in the peri-arrest period are associated with poor outcomes.

Therapeutic Plasma Exchange in Neonatal Septic Shock: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to examine the use of therapeutic plasma exchange (TPE) as adjunctive therapy in neonatal septic shock. STUDY DESIGN: This retrospective cohort study was performed on a convenience sample of neonates in a quaternary children's hospital between January 2018 and February 2019. RESULTS: We identified three neonates with septic shock who received TPE. Two neonates had adenovirus sepsis, and one had group B streptococcal sepsis. All neonates were on extracorporeal life support (ECLS) when TPE was started. The median duration of TPE was 6 days (interquartile range [IQR]: 3-15), with a median of four cycles (IQR: 3-5). Lactate levels decreased significantly after TPE (median before TPE: 5.4 mmol/L [IQR: 2.4-6.1] vs. median after TPE: 1.2 mmol/L [IQR: 1.0-5.8]; p < 0.001). Platelet levels did not change (median before TPE: 73,000/mm3 [IQR: 49,000-100,000] vs. median after TPE: 80,000/mm3 (IQR: 62,000-108,000); p = 0.2). Organ failure indices improved after TPE in two of the three neonates. Hypocalcemia was seen in all cases despite prophylactic calcium infusions. One neonate died, and two survived to ICU discharge. CONCLUSION: TPE can be safely performed in neonates with septic shock. TPE may have a role as an adjunctive therapy in neonates with septic shock requiring ECLS.

The use of extracorporeal membrane oxygenation in human immunodeficiency virus-positive patients: a review of a multicenter database.

AIM: We chose to evaluate the survival of extracorporeal membrane oxygenation among patients with human immunodeficiency virus in a multicenter registry. METHODS: Retrospective case review of the Extracorporeal Life Support Organization Registry respiratory failure of all patients with human immunodeficiency virus supported with extracorporeal membrane oxygenation. RESULTS: A total of 126 patients were included. Survival to discharge was 36%. Eight infants were supported with extracorporeal membrane oxygenation and three (37.5%) survived to discharge. Respiratory extracorporeal membrane oxygenation was the primary indication (78%) with a 39% survival, while cardiac and extracorporeal cardiopulmonary resuscitation indications accounted for 16% and 6% of patients with survivals of 30% and 12.5%, respectively. These differences did not reach significance. There were no significant differences between survivors and non-survivors in demographic data, but non-survivors had significantly more non-human immunodeficiency virus pre-extracorporeal membrane oxygenation infections than survivors. There were no differences in other pre-extracorporeal membrane oxygenation supportive therapies, mechanical ventilator settings, or arterial blood gas results between survivors and non-survivors. The median duration of mechanical ventilation prior to cannulation was 52 (interquartile range: 13-140) hours, while the median duration of the extracorporeal membrane oxygenation exposure was 237 (interquartile range: 125-622) hours. Ventilator settings were significantly lower after 24 hours compared to pre-extracorporeal membrane oxygenation settings. Complications during extracorporeal membrane oxygenation exposure including receipt of renal replacement therapy, inotropic infusions, and cardiopulmonary resuscitation were more common among non-survivors compared to survivors. Central nervous system complications were rare. CONCLUSION: Survival among patients with human immunodeficiency virus infection who receive extracorporeal membrane oxygenation was less than 40%. Infections before extracorporeal membrane oxygenation cannulation occurred more often in non-survivors. The receipt of renal replacement therapy, inotropic infusions, or cardiopulmonary resuscitation during extracorporeal membrane oxygenation was associated with worse outcome.

Variability in Antibiotic Use Across PICUs.

OBJECTIVES: To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability. DESIGN: Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System. SETTING: Forty-one freestanding children's hospital. SUBJECTS: Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System. INTERVENTIONS: To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use. RESULTS: The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared by all 41 PICUs. CONCLUSIONS: The wide variation in antibiotic use observed across children's hospital PICUs suggests inappropriate antibiotic use.

Venovenous extracorporeal life support in patients with HIV infection and Pneumocystis jirovecii pneumonia.

AIM: As experience with extracorporeal life support (ECLS) increases, indications for its use have expanded to diverse patient populations, including those with HIV infection. Pneumocystis jirovecii pneumonia (PJP) is a particularly devastating complication of HIV infections. The objective of this study was to review ECLS use in HIV-positive patients, with particular emphasis on those with concomitant PJP infection. METHODS: All patients were treated by the same ECLS team, consisting of an ECLS specialist intensivist, cardiothoracic surgeon and allied medical professionals at three healthcare institutions. The same ECLS protocol was utilized for all patients during the study period. A retrospective review was performed for all HIV-positive patients placed on ECLS from May 2011 to October 2014. Demographic, clinical, ECLS and complication data were reviewed to identify risk factors for death. RESULTS: A total of 22 HIV-positive patients received ECLS therapy during the study period. All patients were supported with venovenous ECLS and overall survival to hospital discharge was 68%. Survival amongst the PJP positive cohort was 60%. Non-survivors were more likely to require inotropic medications on ECLS (100% non-survivors vs. 46.7% survivors, p=0.022) and had a longer total duration of ECLS (13 days non-survivors vs. 7 days survivors, p=0.011). No difference was observed between PJP-positive and PJP-negative patients with regard to demographic data, complication rates or survival. CONCLUSION: ECLS is a viable treatment option in carefully selected HIV-positive patients, including those with severe disease as manifested by PJP infection.

Shifting Risks and Conflicting Outcomes-ECMO for Neonates with Congenital Diaphragmatic Hernia in the Modern Era.

OBJECTIVES: To update previously described trends for neonates with congenital diaphragmatic hernia (CDH) receiving ECMO with changes in recommendations for care, and to determine how recent advancements in respiratory care have affected this patient population. STUDY DESIGN: This study is a retrospective review of more than 2500 neonates with CDH who received ECMO listed in the Extracorporeal Life Support Organization (ELSO) registry. Cochran-Armitage and multivariate regression analyses were used to analyze changes in the patient population over time and in mortality-related risk factors. RESULTS: Almost one-half (48.1%) of the term neonates survived to discharge, representing a 13.8% decline in survival over the past 25 years (P < .0001). Over the past 10 years, the prevalence of respiratory acidosis more than doubled (P < .0001) and the prevalence of major complications increased (P < .001). During the same period, the number of ECMO courses longer than 1 week increased (P < .001), whereas the prevalence of multiple complications (>4) decreased (P < .0001). Surgeries performed on ECMO were associated with worse outcomes than those performed off ECMO. ECMO duration no longer represents a mortality-related risk factor. CONCLUSIONS: Survival rates for neonates with CDH receiving ECMO have continued to drop in the modern era. Although the safety of ECMO has improved over the last decade, the number of patients experiencing significant respiratory acidosis has more than doubled-increasing the risk of intracranial hemorrhage and overall mortality. The evidence for permissive hypercapnia remains mixed; nonetheless, we believe that the risks outweigh the rewards in this patient population.

Pediatric Intubation by Paramedics in a Large Emergency Medical Services System: Process, Challenges, and Outcomes.

STUDY OBJECTIVE: Pediatric intubation is a core paramedic skill in some emergency medical services (EMS) systems. The literature lacks a detailed examination of the challenges and subsequent adjustments made by paramedics when intubating children in the out-of-hospital setting. We undertake a descriptive evaluation of the process of out-of-hospital pediatric intubation, focusing on challenges, adjustments, and outcomes. METHODS: We performed a retrospective analysis of EMS responses between 2006 and 2012 that involved attempted intubation of children younger than 13 years by paramedics in a large, metropolitan EMS system. We calculated the incidence rate of attempted pediatric intubation with EMS and county census data. To summarize the intubation process, we linked a detailed out-of-hospital airway registry with clinical records from EMS, hospital, or autopsy encounters for each child. The main outcome measures were procedural challenges, procedural success, complications, and patient disposition. RESULTS: Paramedics attempted intubation in 299 cases during 6.3 years, with an incidence of 1 pediatric intubation per 2,198 EMS responses. Less than half of intubations (44%) were for patients in cardiac arrest. Two thirds of patients were intubated on the first attempt (66%), and overall success was 97%. The most prevalent challenge was body fluids obscuring the laryngeal view (33%). After a failed first intubation attempt, corrective actions taken by paramedics included changing equipment (33%), suctioning (32%), and repositioning the patient (27%). Six patients (2%) experienced peri-intubation cardiac arrest and 1 patient had an iatrogenic tracheal injury. No esophageal intubations were observed. Of patients transported to the hospital, 86% were admitted to intensive care and hospital mortality was 27%. CONCLUSION: Pediatric intubation by paramedics was performed infrequently in this EMS system. Although overall intubation success was high, a detailed evaluation of the process of intubation revealed specific challenges and adjustments that can be anticipated by paramedics to improve first-pass success, potentially reduce complications, and ultimately improve clinical outcomes.

Antithrombin Concentrate Use in Pediatric Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVE: To describe antithrombin concentrate use and to compare thrombotic and hemorrhagic outcomes throughout the hospital stay in pediatric subjects who received extracorporeal membrane oxygenation in a Pediatric Health Information System-participating children's hospital. DESIGN: Retrospective, multi-center, cohort study. SETTING: Forty-three free-standing children's hospitals participating in Pediatric Health Information System. SUBJECTS: Children older than or equal to 18 years of age who underwent extracorporeal membrane oxygenation between 2003 and 2012. INTERVENTIONS: Subjects were classified as receiving antithrombin if they received at least one dose of antithrombin while on extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: International Classification of Diseases, Ninth Revision, Clinical Modification codes codes were used to identify hemorrhagic and thrombotic complications during their hospitalization. Pediatric Health Information System data were analyzed to determine hospital-length of stay and in-hospital mortality. A total of 1,931 of 8,601 eligible subjects (21.5%) received at least one dose of antithrombin during their extracorporeal membrane oxygenation course. Antithrombin use during extracorporeal membrane oxygenation increased from 2.4% to 51.9% (p < 0.001) over the 10-year study period. Subjects who received antithrombin while on extracorporeal membrane oxygenation were younger (p = 0.02), had more chronic conditions (p < 0.001), and longer hospital stays (p < 0.001). On multivariate analysis, antithrombin use was associated with thrombotic events (odds ratio, 1.55; 95% CI, 1.36-1.77; p < 0.001), hemorrhagic events (odds ratio, 1.27; 95% CI, 1.14-1.42; p < 0.001), and longer hospital length of stays (slope coefficient, 1.05 d; 95% CI, 1.04-1.06; p < 0.001). No difference was observed in mortality (odds ratio, 0.99; 95% CI, 0.89-1.11; p = 0.90). CONCLUSIONS: In this multicenter retrospective cohort study, subjects who received antithrombin during extracorporeal membrane oxygenation had a higher number of thrombotic and hemorrhagic events throughout the hospitalization and longer length of stays without an associated difference in mortality. While limitations exist with this analysis and results should be interpreted with caution, the fact remains that over half of pediatric patients on extracorporeal membrane oxygenation are currently receiving antithrombin without clear benefit, with extra cost, and potential harms, there needs to be strong consideration for a clinical trial.

Impact of Kidney Disease on Survival in Neonatal Extracorporeal Life Support.

OBJECTIVE: To investigate the prevalence and survival to discharge of neonates with kidney disease who received extracorporeal life support. DESIGN: We analyzed the Extracorporeal Life Support Organization international registry of neonates (< 30 d old) who received extracorporeal life support from 1989 to 2012. We used International Classification of Diseases and Related Health Problems, 9th Revision, Clinical Modification, codes to identify neonates with kidney disease at time of cannulation for extracorporeal life support. SETTING: Participating Extracorporeal Life Support Organization centers. PATIENTS: All neonates who received extracorporeal life support at an Extracorporeal Life Support Organization center from 1989 to 2012. INTERVENTIONS: We performed bivariate logistic regression to estimate associations between survival and covariates. We used unadjusted and adjusted logistic regression to compare survival to discharge between neonates with and without kidney disease. Odds ratios were estimated separately for three groups based on extracorporeal life support indication: pulmonary indication without congenital diaphragmatic hernia, pulmonary indication with congenital diaphragmatic hernia, and cardiac indication. Adjusted models included covariates identified as significant in bivariate models for each group. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was survival to discharge from hospitalization. Of the 28,755 neonates who received extracorporeal life support, 405 had kidney disease (extracorporeal life support indication: 210 pulmonary indication without congenital diaphragmatic hernia, 65 pulmonary indication with congenital diaphragmatic hernia, and 130 cardiac indication). Survival was lower in neonates with kidney disease than those without (49% vs 82% pulmonary indication without congenital diaphragmatic hernia, 25% vs 51% pulmonary indication with congenital diaphragmatic hernia, 21% vs 41% cardiac indication). Kidney disease was associated with reduced survival in adjusted models (95% CI for odds ratio 0.31-0.59 pulmonary indication without congenital diaphragmatic hernia, 0.27-0.89 pulmonary indication with congenital diaphragmatic hernia, 0.31-0.77 cardiac indication). CONCLUSIONS: Neonates with kidney disease who receive extracorporeal life support have poorer survival to discharge compared with other neonates who receive extracorporeal life support, suggesting that kidney disease should be considered when making extracorporeal life support initiation decisions.

Antithrombin concentrates use in children on extracorporeal membrane oxygenation: a retrospective cohort study.

OBJECTIVE: To investigate whether receipt of any antithrombin concentrate improves laboratory and clinical outcomes in children undergoing extracorporeal membrane oxygenation for respiratory failure during their hospitalization compared with those who did not receive antithrombin. DESIGN: Retrospective cohort study. SETTING: Single, tertiary-care pediatric hospital. PATIENTS: Sixty-four neonatal and pediatric patients who underwent extracorporeal membrane oxygenation for respiratory failure between January 2007 and September 2011. INTERVENTION: Exposure to any antithrombin concentrate during their extracorporeal membrane oxygenation course compared with similar children who never received antithrombin concentrate. MEASUREMENTS AND MAIN RESULTS: Thirty patients received at least one dose of antithrombin during their extracorporeal membrane oxygenation course and 34 patients did not receive any. The median age at admission was less than 1-month old. Age, duration of extracorporeal membrane oxygenation, or first antithrombin level did not differ significantly between the two cohorts. The mean plasma antithrombin level in those who never received antithrombin was 42.2% compared with 66% in those who received it. However, few levels reached the targeted antithrombin level of 120% and those who did fell back to deficient levels within an average of 6.8 hours. For those who received antithrombin concentrate, heparin infusion rates decreased by an average of 10.2 U/kg/hr for at least 12 hours following administration. No statistical differences were noted in the number of extracorporeal membrane oxygenation circuit changes, in vivo clots or hemorrhages, transfusion requirements, hospital or ICU length of stay, or in-hospital mortality. CONCLUSIONS: Intermittent, on-demand dosing of antithrombin concentrate in pediatric patients on extracorporeal membrane oxygenation for respiratory failure increased antithrombin levels, but not typically to the targeted level. Patients who received antithrombin concentrate also had decreased heparin requirements for at least 12 hours after dosing. However, no differences were noted in the measured clinical endpoints. A prospective, randomized study of this intervention may require different dosing strategies; such a study is warranted given the unproven efficacy of this costly product.

Outcome of pediatric hematopoietic stem cell transplant recipients requiring mechanical ventilation.

PURPOSE: To assess the risk factors for intensive care unit admission among children receiving hematopoietic stem cell transplantation (HSCT) and to test the hypothesis that multiple organ failure (MOF) increases the odds of death among HSCT patients who receive mechanical ventilation (MV). METHODS: The chart of all consecutive HSCTs at Seattle Children's Hospital and pediatric HSCT patients admitted to the pediatric critical care unit of a tertiary care pediatric hospital from January 2000 to September 2006 were reviewed retrospectively. RESULTS: Charts of 266 HSCT patients were reviewed. Nonmalignant disease compared to hematologic malignancy, acute graft versus host disease grades III and IV, and second transplant increased the odds of pediatric intensive care unit admission. Among patients receiving MV for >24 hours, 9 (25%) survived for 6 months, while 8 patients (22%) were long-term survivors with a median follow-up time of 3.6 years, a significant improvement compared to a long-term survival of 7% (odds ratio 0.25, 95% confidence intervals: 0.09-0.72, P = .01) reported in a previously published cohort of pediatric HSCT patients at the same institution from 1983 to 1996. Cardiovascular failure, duration of MV for greater than 1 week, and prolonged receipt of continuous renal replacement therapy (CRRT) increased the risk of mortality. CONCLUSIONS: Six-month survival of pediatric HSCT patients was 25% and the odds of death were increased by cardiovascular failure but not by MOF. Receipt of mechanical support (ventilation, CRRT) or cardiovascular support (inotropic agents) decreased the likelihood of long-term survival.

Extracorporeal cardiopulmonary resuscitation outcomes in term and premature neonates*.

OBJECTIVE: Extracorporeal cardiopulmonary resuscitation appears to improve survival in patients with acute refractory cardiopulmonary failure. This analysis was performed to determine survival outcomes and predictors of in-hospital mortality for term and preterm neonates who received extracorporeal cardiopulmonary resuscitation. DESIGN: Retrospective review of data from the Extracorporeal Life Support Organization international registry. SETTING: Pediatric and neonatal ICUs. PATIENTS: Infants less than or equal to 30 days. INTERVENTIONS: Extracorporeal cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and survival data from patients who received extracorporeal cardiopulmonary resuscitation between 1998 and 2010 were analyzed to determine factors that affect in-hospital mortality. Overall survival to hospital discharge for the 641 neonates who received extracorporeal cardiopulmonary resuscitation was 39%. In univariate analysis, gestational age correlated inversely with stroke (odds ratio, 0.84 [95% CI, 0.75-0.95]; p = 0.006) and death (odds ratio, 0.87 [95% CI, 0.78-0.96]; p = 0.005) as did corrected gestational age (odds ratio, 0.89 [95% CI, 0.81-0.97]; p = 0.006) and birth weight (odds ratio, 0.53 [95% CI, 0.38-0.74]; p < 0.001). Dysrhythmia as the primary diagnosis had significantly lower odds of death than single-ventricle cardiac disease (odds ratio, 0.24 [95% CI, 0.06-0.95]; p = 0.04). Higher pre-extracorporeal cardiopulmonary resuscitation oxygenation decreased the odds of death (odds ratio, 0.996 [95% CI, 0.994-0.999]; p = 0.01), whereas complications occurring on extracorporeal life support increased the odds of death. In the multivariate analysis, lower birth weight and pre-extracorporeal cardiopulmonary resuscitation oxygenation, as well as complications including CNS hemorrhage, pulmonary hemorrhage, acidosis, renal replacement therapy, and mechanical complications, increased the odds of death. CONCLUSIONS: Overall survival for neonates receiving extracorporeal cardiopulmonary resuscitation is similar to older pediatric patients but decreases with lower gestational age and weight. Despite this, many low-birth weight neonates survive to hospital discharge.