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Τρίτη 5 Νοεμβρίου 2019

Achieving Sustainability in Reducing Unplanned Extubations in a Pediatric Cardiac ICU
Objectives: To determine the incidence of unplanned extubations in a pediatric cardiac ICU in order to prove sustainability of our previously implemented quality improvement initiative. Additionally, we sought to identify risk factors associated with unplanned extubations as well as review the overall outcome of this patient population. Design: Retrospective chart review. Setting: Pediatric cardiac ICU at Children’s Hospital of Colorado on the Anschutz Medical Center of the University of Colorado. Patients: Intubated and mechanically ventilated patients in the cardiac ICU from July 2011 to December 2017. Interventions: None. Measurements and Main Results: A total of 2,612 hospitalizations for 2,067 patients were supported with mechanical ventilation. Forty-five patients had 49 episodes of unplanned extubations (four patients > 1 unplanned extubation). The average unplanned extubation rate per 100 ventilator days was 0.4. Patients who had an unplanned extubation were younger (0.09 vs 5.45 mo; p < 0.001), weighed less (unplanned extubation median weight of 3.0 kg [interquartile range, 2.5–4.5 kg] vs control median weight of 6.0 kg [interquartile range, 3.5–13.9 kg]) (p < 0.001), and had a longer length of mechanical ventilation (8 vs 2 d; p < 0.001). Patients who had an unplanned extubation were more likely to require cardiopulmonary resuscitation during their hospital stay (54% vs 18%; p < 0.001) and had a higher likelihood of in-hospital mortality (15% vs 7%; p = 0.001). There was a significant difference in surgical acuity as denoted by The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score and patients with an unplanned extubation had a higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category (p = 0.019). Contributing factors associated with unplanned extubation were poor endotracheal tube tape integrity, inadequate tube securement, and/or inadequate sedation. A low rate of unplanned extubation was maintained even in the setting of increasing patient complexity and an increase in patient volume. Conclusions: A low rate of unplanned extubation is sustainable even in the setting of increased patient volume and acuity. Additionally, early identification of patients at higher risk of unplanned extubation may also contribute to decreasing the incidence of unplanned extubation. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: nina.censoplano@childrenscolorado.org This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Prevalence and Outcomes of Pediatric In-Hospital Cardiac Arrest Associated With Pulmonary Hypertension
Objectives: In adult in-hospital cardiac arrest, pulmonary hypertension is associated with worse outcomes, but pulmonary hypertension–associated in-hospital cardiac arrest has not been well studied in children. The objective of this study was to determine the prevalence of pulmonary hypertension among children with in-hospital cardiac arrest and its impact on outcomes. Design: Retrospective single-center cohort study. Setting: PICU of a quaternary care, academic children’s hospital. Patients: Children (<18 yr old) receiving greater than or equal to 1 minute of cardiopulmonary resuscitation (cardiopulmonary resuscitation) for an index in-hospital cardiac arrest with an echocardiogram in the 48 hours preceding in-hospital cardiac arrest, excluding those with cyanotic congenital heart disease. Interventions: None. Measurements and Main Results: Of 284 in-hospital cardiac arrest subjects, 57 (20%) had evaluable echocardiograms, which were analyzed by a cardiologist blinded to patient characteristics. Pulmonary hypertension was present in 20 of 57 (35%); nine of 20 (45%) had no prior pulmonary hypertension history. Children with pulmonary hypertension had worse right ventricular systolic function, measured by fractional area change (p = 0.005) and right ventricular global longitudinal strain (p = 0.046); more right ventricular dilation (p = 0.010); and better left ventricular systolic function (p = 0.001). Children with pulmonary hypertension were more likely to have abnormal baseline functional status and a history of chronic lung disease or acyanotic congenital heart disease and less likely to have sepsis or acute kidney injury. Children with pulmonary hypertension were more likely to have an initial rhythm of pulseless electrical activity or asystole and were more frequently treated with inhaled nitric oxide (80% vs 32%; p < 0.001) at the time of cardiopulmonary resuscitation. On multivariable analysis, pulmonary hypertension was not associated with event survival (14/20 [70%] vs 24/37 [65%]; adjusted odds ratio, 1.30 [CI95, 0.25–6.69]; p = 0.77) or survival to discharge (8/20 [40%] vs 10/37 [27%]; adjusted odds ratio, 1.17 [CI95, 0.22–6.44]; p = 0.85). Conclusions: Pulmonary hypertension physiology preceding pediatric in-hospital cardiac arrest may be more common than previously described. Among this cohort with a high frequency of inhaled nitric oxide treatment during cardiopulmonary resuscitation, pulmonary hypertension was not associated with survival outcomes. 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 research funds from the Department of Anesthesiology and Critical Care Medicine at the Children’s Hospital of Philadelphia. Dr. Morgan disclosed that this work was internally funded by the Department of Anesthesiology and Critical Care Medicine at the Children’s Hospital of Philadelphia. His institution received funding from National Institutes of Health (NIH) National Institute of Child Health and Human Development (NICHD) and the NIH National Heart, Lung, and Blood Institute (NHLBI), and he is a member of the American Heart Association (AHA) Emergency Cardiovascular Care Committee. Dr. Kilbaugh’s institution received funding from the Department of Defense, NHLBI, National Institute of Neurological Disorders and Stroke, and Mallinckrodt Pharmaceuticals. Dr. McGowan’s institution received funding from Merck and Transonic Systems, and he received funding from Merck. Dr. Berg’s institution received support from the NICHD and NHLBI. Dr. Sutton’s institution received funding from the NICHD, NHLBI, and Mallinckrodt Pharmaceuticals; he received funding from Zoll Medical (speaking honoraria); he was a member of the 2015 and 2018 AHA Pediatric Advanced Life Support writing group; he is the Chair of the AHA’s Get with the Guidelines-Resuscitation Registry Pediatric Research Task Force; and he disclosed that he is a member of the following subcommittees of the AHA Emergency Cardiovascular Care Committee: Systems of Care, Pediatric Emphasis Group, and Science Review Committee. Dr. Himebauch received funding from the Society of Critical Care Medicine (payment and travel expenses for teaching pediatric bedside ultrasound courses). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: morganr1@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Changes in Provider Perceptions Regarding Early Mobility in the PICU
Objectives: Early mobility in the PICU is safe and feasible. However, PICUs continue to meet barriers to implementing early mobility. PICU providers were surveyed before and after initiating an early mobility protocol to determine perceived barriers and continued challenges in performing early mobility. Design: This single-center prospective study surveyed PICU providers regarding 26 potential barriers to early mobility using a five-point Likert scale. A survey was distributed 1 month prior to and 6 months after beginning an early mobility protocol. Setting: Free-standing academic tertiary care children’s hospital. Subjects: PICU providers of various professions. Interventions: Implementation of PICU-wide early mobility protocol. Measurements and Main Results: Paired pre- and post-early mobility protocol implementation surveys from 97 providers were compared. System-based barriers decreased after implementation of the early mobility protocol, such as lack of guidelines (75–20%; p < 0.01), inadequate training (74–33%; p < 0.01), lack of early mobility orders (72–30%; p < 0.01), and delayed recognition of early mobility candidates (68–35%; p < 0.01). Difficulty coordinating early mobility sessions, although significantly decreased, still remained a concern for 66% of providers in the postsurvey. Lack of resources, specifically staff (85–82%; p = 0.68) and equipment (67–60%; p = 0.36), also remained significant barriers. Presence of an endotracheal tube was a barrier for only 29% of providers’ post-early mobility protocol, compared with 69% prior (p < 0.01). Clinical instability remained a top concern (82–79%; p = 0.63) as well as agitation (74–67%; p = 0.23). Day shift providers, with more early mobility exposure, perceived fewer barriers compared with night shift providers. Ninety percentage of post-early mobility survey participants felt that early mobility positively impacted their patients. Conclusions: Implementation of an early mobility protocol significantly changed provider perceptions regarding barriers to early mobility. Certain factors, such as staff availability, coordination difficulty, equipment shortage, and patient clinical factors, continue to be significant challenges to early mobility in the PICU population. This work was performed at the Monroe Carell Jr. Children’s Hospital at Vanderbilt. 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). Vanderbilt Institute of Translational and Clinical Research provided a $2,000 grant used to purchase Early Mobility equipment for this study. Ms. Hanna received funding from Society of Critical Care Medicine (conference fees). Ms. Hanna and Dr. Betters received funding from Vanderbilt Institute of Translational and Clinical Research (for Early Mobility equipment only). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kristina.betters@vanderbilt.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
The Prognostic Value of Early Amplitude-Integrated Electroencephalography Monitoring After Pediatric Cardiac Arrest
Objectives: To assess the ability of amplitude-integrated electroencephalography monitoring within 24 hours of the return of spontaneous circulation to prognosticate neurologic outcomes in children following cardiac arrest Design: Retrospective review of prospectively recorded data. An amplitude-integrated electroencephalography background score was calculated according to background activity during the first 24 hours after return of spontaneous circulation, a higher score correlating with more impaired background activity. The primary endpoint was the neurologic outcome as defined by the Pediatric Cerebral Performance Category at PICU discharge (Pediatric Cerebral Performance Category 1–3: a good neurologic outcome; Pediatric Cerebral Performance Category 4–6: a poor neurologic outcome). Setting: A referral PICU. Patients: Thirty children with a median age of 10 months (2–38 mo) and a male/female sex ratio of 1.3 were included. Interventions: None. Measurements and Main Results: Eighteen patients were assigned to the favorable outcome group and 12 to the unfavorable outcome group. The median time between return of spontaneous circulation and amplitude-integrated electroencephalography initiation was 4 hours (3–9 hr). The amplitude-integrated electroencephalography score within 24 hours after return of spontaneous circulation was significantly higher in the children with poor outcomes compared with those with good outcomes (12 ± 4 vs 25 ± 8; p < 0.001). Background activity during amplitude-integrated electroencephalography monitoring was able to predict poor neurologic outcomes at PICU discharge, with an area under the receiver operating characteristic curve of 0.91 (95% CI, 0.81–1.00). Conclusions: Early amplitude-integrated electroencephalography monitoring may help predict poor neurologic outcomes in children within 24 hours following cardiac arrest. The authors have disclosed that they do not have any potential conflict of interest. This study was conducted at Nantes University Hospital, France. For information regarding this article, E-mail: Pierre.bourgoin@chu-nantes.fr ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Oxygenator Impact on Ceftolozane and Tazobactam in Extracorporeal Membrane Oxygenation Circuits
Objectives: To determine the oxygenator impact on alterations of ceftolozane/tazobactam in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane oxygenation circuit including the Quadrox-i oxygenator (Maquet, Wayne, NJ). Design: A 1/4-inch and 3/8-inch, simulated closed-loop extracorporeal membrane oxygenation circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of ceftolozane/tazobactam was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24-hour time points. Ceftolozane/tazobactam was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation Setting: A free-standing extracorporeal membrane oxygenation circuit. Patients: None. Interventions: Single-dose administration of ceftolozane/tazobactam into closed-loop extracorporeal membrane oxygenation circuits prepared with and without an oxygenator in series with serial preoxygenator, postoxygenator, and reference samples obtained for concentration determination over a 24-hour study period. Measurements and Main Results: For the 1/4-inch circuit, there was approximately 92% ceftolozane and 22–25% tazobactam loss with the oxygenator in series and 19–30% ceftolozane and 31–34% tazobactam loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was approximately 85% ceftolozane and 29% tazobactam loss with the oxygenator in series and 25–27% ceftolozane and 23–26% tazobactam loss without an oxygenator in series at 24 hours. The reference ceftolozane and tazobactam concentrations remained relatively constant during the entire study period demonstrating the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation. Conclusions: This ex vivo investigation demonstrated substantial ceftolozane loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and significant ceftolozane loss in the absence of an oxygenator. Tazobactam loss was similar regardless of the presence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific drug dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation. Presented, in part, at the abstract presentation of the 2018 Society of Critical Care Medicine Annual Congress, February 25-28, 2018, San Antonio, TX. Supported, in part, by grant from Merck. Dr. Cies received funding from Merck (who supplied the drug for this study) and Atlantic Diagnostic Laboratories (consultant). He also received funding from Allergan, Melinta, and Thermo Fisher as a consultant (unrelated to this work).The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jeffrey.cies@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Effect of Endotracheal Tube Size, Respiratory System Mechanics, and Ventilator Settings on Driving Pressure
Objectives: We sought to investigate factors that affect the difference between the peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions (resistive pressure) during pressure controlled ventilation across a range of endotracheal tube sizes, respiratory mechanics, and ventilator settings. Design: In vitro study. Setting: Research laboratory. Patients: None. Interventions: An in vitro bench model of the intubated respiratory system during pressure controlled ventilation was used to obtain the difference between peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions across a range of endotracheal tubes sizes (3.0–8.0 mm). Measurements were taken at combinations of pressure above positive end-expiratory pressure (10, 15, and 20 cm H2O), airway resistance (no, low, high), respiratory system compliance (ranging from normal to extremely severe), and inspiratory time at constant positive end-expiratory pressure (5 cm H2O). Multiple regression analysis was used to construct models predicting resistive pressure stratified by endotracheal tube size. Measurements and Main Results: On univariate regression analysis, respiratory system compliance (β –1.5; 95% CI, –1.7 to –1.4; p < 0.001), respiratory system resistance (β 1.7; 95% CI, 1.5–2.0; p < 0.001), pressure above positive end-expiratory pressure (β 1.7; 95% CI, 1.4–2.0; p < 0.001), and inspiratory time (β –0.7; 95% CI, –1.0 to –0.4; p < 0.001) were associated with resistive pressure. Multiple linear regression analysis showed the independent association between increasing respiratory system compliance, increasing airway resistance, increasing pressure above positive end-expiratory pressure, and decreasing inspiratory time and resistive pressure across all endotracheal tube sizes. Inspiratory time was the strongest variable associated with a proportional increase in resistive pressure. The contribution of airway resistance became more prominent with increasing endotracheal tube size. Conclusions: Peak inspiratory pressures measured during pressure controlled ventilation overestimated plateau pressure irrespective of endotracheal tube size, especially with decreased inspiratory time or increased airway resistance. 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: m.c.j.kneyber@umcg.nl ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Nosocomial Infections During Extracorporeal Membrane Oxygenation in Neonatal, Pediatric, and Adult Patients: A Comprehensive Narrative Review
Objectives: Extracorporeal membrane oxygenation is increasingly used in critically ill patients with refractory cardiopulmonary failure. Nosocomial infection acquired during extracorporeal membrane oxygenation represents one of the most frequent complications but the available evidence on the risk of infection and its association with outcomes has not been comprehensively analyzed. We performed a narrative review examining the epidemiology of nosocomial infection during extracorporeal membrane oxygenation, association with clinical outcomes, and preventive strategies. Data Sources: We searched PubMed, Web of Science, EMBASE, and the Cochrane Library between 1972 and June 2018. Study Selection: We included any article which detailed nosocomial infection during extracorporeal membrane oxygenation. Articles were excluded if they were not written in English, detailed extracorporeal membrane oxygenation use for infections acquired prior to extracorporeal membrane oxygenation, or used other forms of extracorporeal support such as ventricular assist devices. Data Extraction: Two reviewers independently assessed eligibility and extracted data. We screened 984 abstracts and included 59 articles in the final review. Data Synthesis: The reported risk of nosocomial infection among patients receiving extracorporeal membrane oxygenation ranged from 3.5% to 64% per extracorporeal membrane oxygenation run, while the incidence of infection ranged from 10.1 to 116.2/1,000 extracorporeal membrane oxygenation days. Nosocomial infections during extracorporeal membrane oxygenation were consistently associated with longer duration of extracorporeal membrane oxygenation and, in several large multicenter studies, with increased mortality. Risk factors for nosocomial infection included duration of extracorporeal membrane oxygenation, mechanical and hemorrhagic complications on extracorporeal membrane oxygenation, and use of venoarterial and central extracorporeal membrane oxygenation. Biomarkers had low specificity for infection in this population. Few studies examined strategies on how to prevent nosocomial infection on extracorporeal membrane oxygenation. Conclusions: Nosocomial infections in extracorporeal membrane oxygenation patients are common and associated with worse outcomes. There is substantial variation in the rates of reported infection, and thus, it is possible that some may be preventable. The evidence for current diagnostic, preventive, and therapeutic strategies for infection during extracorporeal membrane oxygenation is limited and requires further investigation. Supplemental digital content is available for this article. Direct URL citationsappear 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: gmaclaren@iinet.net.au ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Prevalence and Outcomes of Balloon Atrial Septostomy in Neonates With Transposition of Great Arteries
Objectives: Transposition of the great arteries is the most common cyanotic congenital heart defect. Surgical correction usually occurs in the first week of life; presence of restrictive interatrial communication and severe hypoxemia warrants urgent intervention with balloon atrial septostomy and medical stabilization prior to surgery. The main objective of this study is to compare the characteristics, outcomes, and mortality risks in patients with transposition of the great arteries who underwent balloon atrial septostomy during their hospitalization versus transposition of the great arteries patients who have not undergone this procedure. Design: Retrospective analysis of administrative data. Setting: Data from Kids’ Inpatient Database complemented with the National Inpatient Sample dataset for the years 1998–2014, this includes data from participating hospitals in 47 U.S. States and the District of Columbia. Patients: Neonates admitted with transposition of the great arteries. Interventions: None. Measurements and Main Results: A total of 17,392 neonates with diagnosis of transposition of the great arteries were captured in the databases we used. Male-to-female ratio was 2:1. The rate of balloon atrial septostomy in patients with transposition of the great arteries was 27.7% without significant change over the years. There was no significant difference in mortality between balloon atrial septostomy and no balloon atrial septostomy (6.3% vs 6.7%; p = 0.29). Neonates with balloon atrial septostomy had a two-fold increase in their length of stay compared with no balloon atrial septostomy (16 d vs 7 d; p < 0.0001). Stroke was present in 1.1% of balloon atrial septostomy group versus 0.6% in those who did not have balloon atrial septostomy (odds ratio, 1.85; 95% CI, 1.29–2.65; p < 0.0001). Extracorporeal membrane oxygenation was used more in balloon atrial septostomy group (5.1% vs 3.1%; p < 0.0001). Conclusions: There was no difference in mortality rate between balloon atrial septostomy and no balloon atrial septostomy patients. The prevalence of the diagnosis of stroke in this study was higher in patients who underwent balloon atrial septostomy. Furthermore, comparison of in-hospital mortality in balloon atrial septostomy and no balloon atrial septostomy revealed increased mortality risk in no balloon atrial septostomy patients transferred from other institution, no balloon atrial septostomy patients supported with extracorporeal membrane oxygenation, and balloon atrial septostomy patients diagnosed with stroke. Finally, length of stay and charges were higher in balloon atrial septostomy patients. Dr. Hamzah conceptualized and designed the study and drafted the initial article. Dr. Othman carried out the analyses, reviewed, and revised the article. Drs. Peluso and Sammour reviewed and revised the article. Dr. Aly conceptualized and designed the study and critically reviewed the article for important intellectual content. All authors approved the final article as submitted and agree to be accountable for all aspects of the work. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: HamzahM@ccf.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Catheter-Directed Pharmacologic Thrombolysis for Acute Submassive and Massive Pulmonary Emboli in Children and Adolescents—An Exploratory Report
Objectives: The objective of this study is to report a single-center experience of the safety and efficacy of pulmonary artery catheter-directed thrombolysis for both massive and submassive pulmonary emboli in the pediatric and adolescent population. Design: A 22-month retrospective review of the electronic medical record and picture archiving and communication system was performed of patients less than 21 years old, presenting with massive or submassive pulmonary emboli treated with pulmonary artery catheter-directed thrombolysis at a single, tertiary care pediatric hospital. Multiple variables were analyzed including indications, technical success, clinical efficacy, and complications. Setting: A single, tertiary care pediatric hospital. Patients: Nine patients (mean 13.9 yr; range 6–19 yr) with massive and/or submassive pulmonary emboli who underwent pulmonary artery catheter-directed thrombolysis met inclusion criteria. Interventions: Catheter-directed thrombolysis. Measurements and Main Results: Pulmonary emboli was diagnosed by CT angiography in all cases. Catheter-directed thrombolysis alone was clinically successful (defined as improved cardiopulmonary function following catheter-directed thrombolysis) in seven patients (78%) with two patients not improving following catheter-directed thrombolysis. There were no immediate bleeding complications from catheter-directed thrombolysis therapy. All patients were maintained on anticoagulation treatment following catheter-directed thrombolysis. Catheter-directed thrombolysis was technically successful (defined as successful placement of pulmonary artery infusion catheters with full or partial resolution of thrombus) in all cases. Follow-up pulmonary angiography at the cessation of catheter-directed thrombolysis revealed complete thrombus resolution in four patients (44%) and partial resolution in five patients (55%). Mean pulmonary artery pressures decreased in all patients (mean precatheter-directed thrombolysis pulmonary artery pressure = 37 ± 11 mm Hg; mean postcatheter-directed thrombolysis pulmonary artery pressure = 28 ± 10 mm Hg; p = 0.0164). Conclusions: Pulmonary artery catheter-directed thrombolysis is a technically feasible therapeutic option for children and adolescents with submassive and massive pulmonary emboli. Mr. Ji and Dr. Durrence were involved in the literature search, the writing of the article, and the article preparation. Drs. Gill, Shah, and Hawkins were involved in the management of patient care, patient data, literature search, and editing of the article. Drs. Paden, Patel, and Williamson were involved in the management of patient care, data validation, and construction of the article. All authors approved the final article. Dr. Paden disclosed that he is President-elect of Extracorporeal Life Support Organization (no salary involved), has multiple patents for a novel pediatric renal replacement device (not discussed in this manuscript), has received grants from private organizations related to extracorporeal membrane oxygenation research (not discussed in this manuscript), and he disclosed off label product use of the majority of drugs and techniques described in the manuscript in a pediatric population. Dr. Patel’s institution received funding from Pediatric Research Alliance Junior Faculty Focused Pilot Grant; she received funding from Daiichi Sankyo; she disclosed acting as institutional principal investigator for phase 2 and phase 3 clinical trials in children with venous thromboembolism; and she disclosed off-label product use of tissue plasminogen activator for a pediatric population. Dr. Williamson disclosed receiving a departmental grant to study resuscitation of pediatric trauma (unrelated to current work). The remaining authors have disclosed that they do not have any potential conflicts of interest. Written informed consent was obtained from the patients for publication of this case series, including accompanying images. For information regarding this article, E-mail: matt.hawkins@emory.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
Outcomes Associated With Multiple Organ Dysfunction Syndrome in Critically Ill Children With Hyperglycemia
Objectives: Patterns and outcomes of multiple organ dysfunction syndrome are unknown in critically ill children with hyperglycemia. We aimed to determine whether tight glycemic control to a lower vs. higher range influenced timing, duration, or resolution of multiple organ dysfunction syndrome as well as characterize the clinical outcomes of subgroups of multiple organ dysfunction syndrome in children enrolled in the Heart And Lung Failure-Pediatric INsulin Titration trial. Design: Planned secondary analysis of the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. Setting: Thirty-five PICUs. Patients: Critically ill children with hyperglycemia who received the Heart And Lung Failure-Pediatric INsulin Titration protocol from 2012 to 2016. Interventions: Randomization to a lower versus higher glucose target group. Measurements and Main Results: Of 698 patients analyzed, 48 (7%) never developed multiple organ dysfunction syndrome, 549 (79%) had multiple organ dysfunction syndrome without progression, 32 (5%) developed new multiple organ dysfunction syndrome, and 69 (10%) developed progressive multiple organ dysfunction syndrome. Of those whose multiple organ dysfunction syndrome resolved, 192 (34%) experienced recurrent multiple organ dysfunction syndrome. There were no significant differences in the proportion of multiple organ dysfunction syndrome subgroups between Heart And Lung Failure-Pediatric INsulin Titration glucose target groups. However, patients with new or progressive multiple organ dysfunction syndrome had fewer ICU-free days through day 28 than those without new or progressive multiple organ dysfunction syndrome, and progressive multiple organ dysfunction syndrome patients had fewer ICU-free days than those with new multiple organ dysfunction syndrome: median 25.1 days for never multiple organ dysfunction syndrome, 20.2 days for multiple organ dysfunction syndrome without progression, 18.6 days for new multiple organ dysfunction syndrome, and 0 days for progressive multiple organ dysfunction syndrome (all comparisons p < 0.001). Patients with recurrent multiple organ dysfunction syndrome experienced fewer ICU-free days than those without recurrence (median, 11.2 vs 22.8 d; p < 0.001). Conclusions: Tight glycemic control target range was not associated with differences in the proportion of new, progressive, or recurrent multiple organ dysfunction syndrome. New or progressive multiple organ dysfunction syndrome was associated with poor clinical outcomes, and progressive multiple organ dysfunction syndrome was associated with worse outcomes than new multiple organ dysfunction syndrome. In future studies, new multiple organ dysfunction syndrome and progressive multiple organ dysfunction syndrome may need to be considered separately, as they represent distinct subgroups with different, potentially modifiable risk factors. Patients with recurrent multiple organ dysfunction syndrome represent a newly characterized, high-risk group which warrants attention in future research. Members of the Heart And Lung Failure-Pediatric INsulin Titration (HALF-PINT) Study Investigators are listed in the Appendix (Supplemental Digital Content 1, http://links.lww.com/PCC/B101). 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 the National Heart, Lung, and Blood Institute (U01 HL107681 and U01 HL108028). Drs. Marsillio’s, Wypij’s, and Ms. Asaro’s institutions received funding from National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute. Drs. Marsillio, Srinivasan, Wypij, Agus, Nadkarni, and Ms. Asaro received support for article research from the NIH. Dr. Sorce’s institution received funding from the NIH. This work was completed at Ann & Robert H. Lurie Children’s Hospital of Chicago, Boston Children’s Hospital, and Children’s Hospital of Philadelphia based on data from the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. For information regarding this article, E-mail: LMarsillio@luriechildrens.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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