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OBJECTIVES: To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use. DESIGN: Secondary analyses of a multicenter prospective observational cohort study. SETTING: Twelve academic PICUs. PATIENTS: Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2-13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%). CONCLUSIONS: Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients' preexisting conditions.

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OBJECTIVES: The objective of this study was to compare survival outcomes and intra-arrest arterial blood pressures between children receiving cardiopulmonary resuscitation for bradycardia and poor perfusion and those with pulseless cardiac arrests. DESIGN: Prospective, multicenter observational study. SETTING: PICUs and cardiac ICUs of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Children (< 19 yr old) who received greater than or equal to 1 minute of cardiopulmonary resuscitation with invasive arterial blood pressure monitoring in place. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 164 patients, 96 (59%) had bradycardia and poor perfusion as the initial cardiopulmonary resuscitation rhythm. Compared to those with initial pulseless rhythms, these children were younger (0.4 vs 1.4 yr; p = 0.005) and more likely to have a respiratory etiology of arrest (p < 0.001). Children with bradycardia and poor perfusion were more likely to survive to hospital discharge (adjusted odds ratio, 2.31; 95% CI, 1.10-4.83; p = 0.025) and survive with favorable neurologic outcome (adjusted odds ratio, 2.21; 95% CI, 1.04-4.67; p = 0.036). There were no differences in diastolic or systolic blood pressures or event survival (return of spontaneous circulation or return of circulation via extracorporeal cardiopulmonary resuscitation). Among patients with bradycardia and poor perfusion, 49 of 96 (51%) had subsequent pulselessness during the cardiopulmonary resuscitation event. During cardiopulmonary resuscitation, these patients had lower diastolic blood pressure (point estimate, -6.68 mm Hg [-10.92 to -2.44 mm Hg]; p = 0.003) and systolic blood pressure (point estimate, -12.36 mm Hg [-23.52 to -1.21 mm Hg]; p = 0.032) and lower rates of return of spontaneous circulation (26/49 vs 42/47; p < 0.001) than those who were never pulseless. CONCLUSIONS: Most children receiving cardiopulmonary resuscitation in ICUs had an initial rhythm of bradycardia and poor perfusion. They were more likely to survive to hospital discharge and survive with favorable neurologic outcomes than patients with pulseless arrests, although there were no differences in immediate event outcomes or intra-arrest hemodynamics. Patients who progressed to pulselessness after cardiopulmonary resuscitation initiation had lower intra-arrest hemodynamics and worse event outcomes than those who were never pulseless.

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OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

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OBJECTIVES: The objective of this study was to associate ventilation rates during in-hospital cardiopulmonary resuscitation with 1) arterial blood pressure during cardiopulmonary resuscitation and 2) survival outcomes. DESIGN: Prospective, multicenter observational study. SETTING: Pediatric and pediatric cardiac ICUs of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Intubated children (≥ 37 wk gestation and < 19 yr old) who received at least 1 minute of cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure and ventilation rate (breaths/min) were manually extracted from arterial line and capnogram waveforms. Guideline rate was defined as 10 ± 2 breaths/min; high ventilation rate as greater than or equal to 30 breaths/min in children less than 1 year old, and greater than or equal to 25 breaths/min in older children. The primary outcome was survival to hospital discharge. Regression models using Firth penalized likelihood assessed the association between ventilation rates and outcomes. Ventilation rates were available for 52 events (47 patients). More than half of patients (30/47; 64%) were less than 1 year old. Eighteen patients (38%) survived to discharge. Median event-level average ventilation rate was 29.8 breaths/min (interquartile range, 23.8-35.7). No event-level average ventilation rate was within guidelines; 30 events (58%) had high ventilation rates. The only significant association between ventilation rate and arterial blood pressure occurred in children 1 year old or older and was present for systolic blood pressure only (-17.8 mm Hg/10 breaths/min; 95% CI, -27.6 to -8.1; p < 0.01). High ventilation rates were associated with a higher odds of survival to discharge (odds ratio, 4.73; p = 0.029). This association was stable after individually controlling for location (adjusted odds ratio, 5.97; p = 0.022), initial rhythm (adjusted odds ratio, 3.87; p = 0.066), and time of day (adjusted odds ratio, 4.12; p = 0.049). CONCLUSIONS: In this multicenter cohort, ventilation rates exceeding guidelines were common. Among the range of rates delivered, higher rates were associated with improved survival to hospital discharge.

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OBJECTIVE: To investigate the association between body habitus and mortality in critically ill children with sepsis or septic shock. STUDY DESIGN: This was a retrospective cohort study of prospectively collected data of children admitted to US pediatric intensive care units (PICUs) with a primary or secondary diagnosis of sepsis or septic shock. We separated body habitus into underweight, normal weight, overweight, and obese. Outcomes were mortality (primary), treatment with invasive mechanical ventilation (secondary), and time to PICU discharge for survivors (secondary). Multivariable analyses using mixed-effects logistic regression and shared frailty models clustered by unit and adjusted for confounding variables were used to assess the association between body habitus and outcomes. RESULTS: There were 7038 children with sepsis or septic shock. Mortality was 10.1% (n = 714) and 52.9% (n = 3720) required invasive mechanical ventilation. Body habitus was not associated with mortality after controlling for hospital level effects and confounding variables. Children who were overweight and obese had greater odds of invasive mechanical ventilation (overweight OR 1.23 [95% CI 1.05-1.45], P = .011 and obese OR 1.57 [95% CI 1.37-1.80], P < .001) compared with children of normal weight. In survivors treated with invasive mechanical ventilation, children who were obese had a longer time to PICU discharge than children of normal weight (obese hazard ratio for discharge 0.84 [95% CI, 0.77-0.92], P < .0001). CONCLUSIONS: There was no association between body habitus and mortality in critically ill children with sepsis. Children who were overweight and obese were more likely to receive invasive mechanical ventilation and mechanically ventilated survivors who were obsese had a longer time to PICU discharge.

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OBJECTIVE: To use an objective metric of effort of breathing to determine optimal high flow nasal cannula (HFNC) flow rates in children <3 years of age. STUDY DESIGN: Single-center prospective trial in a 24-bed pediatric intensive care unit of children <3 years of age on HFNC. We measured the percent change in pressure∙rate product (PRP) (an objective measure of effort of breathing) as a function of weight-indexed flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/minute. For a subgroup of patients, 2 different HFNC delivery systems (Fisher & Paykel [Auckland, New Zealand] and Vapotherm [Exeter, New Hampshire]) were compared. RESULTS: Twenty-one patients (49 titration episodes) were studied. The most common diagnoses were bronchiolitis and pneumonia. Overall, there was a significant difference in the percent change in PRP from baseline (of 0.5 L/kg/minute) with increasing flow rates for the entire cohort (P < .001) with largest change at 2.0 L/kg/min (-21%). Subgroup analyses showed no significant difference in percent change in PRP from baseline when comparing the 2 different HFNC delivery systems (P = .12). Patients ≤8 kg experienced a larger percent change in PRP as HFNC flow rates were increased (P = .001) than patients >8 kg. CONCLUSIONS: The optimal HFNC flow rate to reduce effort of breathing in infants and young children is approximately 1.5-2.0 L/kg/minute with more benefit seen in children ≤8 kg.

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OBJECTIVE: To directly compare effort of breathing between high flow nasal cannula (HFNC), nasal intermittent mechanical ventilation (NIMV), and nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: This was a single center prospective cross-over study for patients <6 months in the cardiothoracic or pediatric intensive care unit receiving nasal noninvasive respiratory support after extubation. We measured effort of breathing using esophageal manometry with pressure-rate product (PRP) on all 3 modes. NIMV synchrony was determined by comparing patient efforts (esophageal manometry) with mechanically delivered breaths (spirometry in ventilator circuit). On NIMV, PRP and synchrony was also measured after adding a nasal clip on 26 patients. RESULTS: Forty-two children were included. Median (IQR) age was 2 (0.5, 4) months. There was no difference in median PRP between HFNC 6 liters per minute, 355 (270,550), NIMV 12/5 cm H2O, 341 (235, 472), and NCPAP 5 cm H2O, 340 (245,506) (P?=?.33). Results were similar regardless of HFNC flow rate or NIMV inspiratory pressure. Median PRP on CPAP of 5 cm H2O prior to extubation 255 (176, 375) was significantly lower than all postextubation values (P??.07)). However, as NIMV synchrony improved (>60%), PRP on NIMV was lower than on HFNC. CONCLUSIONS: For infants, effort of breathing is similar on HFNC, NIMV, and NCPAP after extubation, regardless of flow rate or inspiratory pressure. We speculate that bi-level NIMV may be superior if high levels of synchrony can be achieved.

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OBJECTIVE: Identify variables independently associated with delivered tidal volume (VT) and measured mean airway pressure during high-frequency oscillatory ventilation across the range of pediatric endotracheal tube sizes. DESIGN: In vitro study. SETTING: Research laboratory. INTERVENTIONS: An in vitro bench model of the intubated pediatric respiratory system during high-frequency oscillatory ventilation was used to obtain delivered VT and mean airway pressure (in the distal lung) for various endotracheal tube sizes. Measurements were taken at different combinations of ventilator set mean airway pressure (Paw), amplitude (ΔP), frequency, and test lung compliance. Multiple regression analysis was used to construct multivariable models predicting delivered VT and mean airway pressure. MEASUREMENTS AND MAIN RESULTS: Variables independently associated with higher delivered VT for all endotracheal tube sizes include higher ΔP (p < 0.001), lower frequency (p < 0.001), and higher test lung compliance (p < 0.001). A multiplicative interaction between frequency and ΔP magnifies the delivered VT when ΔP is high and frequency is low (p < 0.001). Delivered mean airway pressure becomes lower than set Paw as ΔP increases (p < 0.001) and frequency increases (p < 0.05). Ventilator set Paw is the largest determinant of delivered mean airway pressure; however, increasing ΔP resulted in a lower delivered mean airway pressure. For example, in a 4.0 mm ID endotracheal tube, increasing ΔP by 10 cm H2O resulted in an average decrease of delivered mean airway pressure by 4.5%. CONCLUSIONS: This is the first study to quantify the interaction between ΔP and frequency in delivered VT and the effect of ΔP and frequency on delivered mean airway pressure. These results demonstrate the need to measure or estimate VT and delivered pressures during high-frequency oscillatory ventilation and may be useful in determining optimal strategies for lung protective ventilation during high-frequency oscillatory ventilation.

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OBJECTIVE: To investigate differences in sepsis mortality between prepubertal and postpubertal males and females. STUDY DESIGN: This was a retrospective review of the Virtual PICU Systems (VPS) database (including 74 pediatric intensive care units [PICUs]) for 2006-2008. We included prepubertal (aged 2-7 years) and postpubertal (aged 16-21 years) children with a primary diagnosis of sepsis admitted to a participating PICU. RESULTS: Prepubertal females (n = 272; 9.9% mortality) and prepubertal males (n = 303; 10.9% mortality) had similar mortality and severity of illness (Pediatric Index of Mortality 2 risk of mortality [PIM 2 ROM]). Postpubertal females (n = 233; mortality, 5.6%) had lower mortality than postpubertal males (n = 212; mortality, 11.8%; P = .03). PIM 2 ROM was higher for postpubertal males than postpubertal females (P = .02). After controlling for hospital specific effects with multivariate modeling, in postpubertal children, female gender was independently associated with a lower initial severity of illness (PIM 2 ROM: OR, 0.77; 95% CI, 0.62-0.96; P = .02). CONCLUSION: Sepsis mortality is similar in prepubertal males and females. However, postpubertal males have a higher sepsis mortality than postpubertal females, likely related to their greater severity of illness on PICU admission. These outcome differences in postpubertal children may reflect a hormonal influence on the response to infection or differences in underlying comorbidities, source of infection, or behavior.

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OBJECTIVE: To characterize the clinical course, therapies, and outcomes of children with fatal and near-fatal asthma admitted to pediatric intensive care units (PICUs). STUDY DESIGN: This was a retrospective chart abstraction across the 8 tertiary care PICUs of the Collaborative Pediatric Critical Care Research Network (CPCCRN). Inclusion criteria were children (aged 1-18 years) admitted between 2005 and 2009 (inclusive) for asthma who received ventilation (near-fatal) or died (fatal). Data collected included medications, ventilator strategies, concomitant therapies, demographic information, and risk variables. RESULTS: Of the 261 eligible children, 33 (13%) had no previous history of asthma, 218 (84%) survived with no known complications, and 32 (12%) had complications. Eleven (4%) died, 10 of whom had experienced cardiac arrest before admission. Patients intubated outside the PICU had a shorter duration of ventilation (median, 25 hours vs 84 hours; P < .001). African-Americans were disproportionately represented among the intubated children and had a shorter duration of intubation. Barotrauma occurred in 15 children (6%) before admission. Pharmacologic therapy was highly variable, with similar outcomes. CONCLUSION: Of the children ventilated in the CPCCRN PICUs, 96% survived to hospital discharge. Most of the children who died experienced cardiac arrest before admission. Intubation outside the PICU was correlated with shorter duration of ventilation. Complications of barotrauma and neuromyopathy were uncommon. Practice patterns varied widely among the CPCCRN sites.

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OBJECTIVE: To investigate parents' perspectives on the desirability, content, and conditions of a physician-parent conference after their child's death in the pediatric intensive care unit (PICU). STUDY DESIGN: Audio-recorded telephone interviews were conducted with 56 parents of 48 children. All children died in the PICU of one of six children's hospitals in the National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) 3 to 12 months before the study. RESULTS: Only seven (13%) parents had a scheduled meeting with any physician to discuss their child's death; 33 (59%) wanted to meet with their child's intensive care physician. Of these, 27 (82%) were willing to return to the hospital to meet. Topics that parents wanted to discuss included the chronology of events leading to PICU admission and death, cause of death, treatment, autopsy, genetic risk, medical documents, withdrawal of life support, ways to help others, bereavement support, and what to tell family. Parents sought reassurance and the opportunity to voice complaints and express gratitude. CONCLUSIONS: Many bereaved parents want to meet with the intensive care physician after their child's death. Parents seek to gain information and emotional support, and to give feedback about their PICU experience.

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OBJECTIVE: To report our experience with cuffed endotracheal tubes (ETT) in a large cohort of critically ill children. Study design We prospectively collected data over a 1-year period concerning long-term intubation on 860 critically ill children admitted to our intensive care unit. Tube sizes were dictated by the modified Cole formula for uncuffed ETT (age [y]/4+4 mm ID) and chosen one-half size less for cuffed ETT. Cuff pressure was regularly monitored to maintain a small leak at peak inspiratory pressure. The choice of ETT was made by the physician responsible for the initial airway management. RESULTS: There were 597 patients in the first 5 years of life, with 210 having cuffed ETT. There were no significant differences in the use of racemic epinephrine for postextubation subglottic edema, the rate of successful extubation or the need for tracheotomy between those with cuffed and uncuffed ETT in any age group. CONCLUSIONS: Our data suggest that the traditional teaching in pediatric anesthesia and intensive care, including current pediatric life support recommendations, need to be reviewed for children to benefit from the advantages of modern low-pressure cuffed ETT during critical illnesses.

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