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Background: Pediatric Intensive Care Unit (PICU) teams provide care for critically ill children with diverse and often complex medical and surgical conditions. Researchers often lack guidance on an approach to select the best outcomes when evaluating this critically ill population. Studies would be enhanced by incorporating multi-stakeholder preferences to better evaluate clinical care. This manuscript outlines the methodology currently being used to develop a PICU Core Outcome Set (COS). This PICU COS utilizes mixed methods, an inclusive stakeholder approach, and a modified Delphi consensus process that will serve as a resource for PICU research programs., Methods: A Scoping Review of the PICU literature evaluating outcomes after pediatric critical illness, a qualitative study interviewing PICU survivors and their parents, and other relevant literature will serve to inform a modified, international Delphi consensus process. The Delphi process will derive a set of minimum domains for evaluation of outcomes of critically ill children and their families. Delphi respondents include researchers, multidisciplinary clinicians, families and former patients, research funding agencies, payors, and advocates. Consensus meetings will refine and finalize the domains of the COS, outline a battery instruments for use in future studies, and prepare for extensive dissemination for broad implementation., Discussion: The PICU COS will be a guideline resource for investigators to assure that outcomes most important to all stakeholders are considered in PICU clinical research in addition to those deemed most important to individual scientists., Trial Registration: COMET database (http://www.comet-initiative.org/, Record ID 1131, 01/01/18)., Competing Interests: Declaration of Competing Interest The authors declare not competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: The mathematical method used to calculate chest compression (CC) rate during cardiopulmonary resuscitation varies in the literature and across device manufacturers. The objective of this study was to determine the variability in calculated CC rates by applying four published methods to the same dataset., Methods: This study was a secondary investigation of the first 200 pediatric cardiac arrest events with invasive arterial line waveform data in the ICU-RESUScitation Project (NCT02837497). Instantaneous CC rates were calculated during periods of uninterrupted CCs. The defined minimum interruption length affects rate calculation (e.g., if an interruption is defined as a break in CCs ≥ 2 s, the lowest possible calculated rate is 30 CCs/min). Average rates were calculated by four methods: 1) rate with an interruption defined as ≥ 1 s; 2) interruption ≥ 2 s; 3) interruption ≥ 3 s; 4) method #3 excluding top and bottom quartiles of calculated rates. American Heart Association Guideline-compliant rate was defined as 100-120 CCs/min. A clinically important change was defined as ±5 CCs/min. The percentage of events and epochs (30 s periods) that changed Guideline-compliant status was calculated., Results: Across calculation methods, mean CC rates (118.7-119.5/min) were similar. Comparing all methods, 14 events (7%) and 114 epochs (6%) changed Guideline-compliant status., Conclusion: Using four published methods for calculating CC rate, average rates were similar, but 7% of events changed Guideline-compliant status. These data suggest that a uniform calculation method (interruption ≥ 1 s) should be adopted to decrease variability in resuscitation science., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity for children encountering community-acquired septic shock., Design: Prospective, cohort-outcome study, conducted 2013-2017., Setting: Twelve academic PICUs in the United States., Patients: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support., Interventions: Demographic, infection, illness severity, organ dysfunction, and resource utilization data were collected daily during PICU admission. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale., Measurements and Main Results: Among 389 children enrolled, mean age was 7.4 ± 5.8 years; 46% were female; 18% were immunocompromised; and 51% demonstrated chronic comorbidities. Baseline Pediatric Overall Performance Category was normal in 38%. Median (Q1-Q3) Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores at PICU admission were 11.0 (6.0-17.0) and 9.0 (6.0-11.0); durations of vasoactive-inotropic and mechanical ventilation support were 3.0 days (2.0-6.0 d) and 8.0 days (5.0-14.0 d); and durations of PICU and hospital stay were 9.4 days (5.6-15.4 d) and 15.7 days (9.2-26.0 d). At 1, 3, 6, and 12 months following PICU admission for the septic shock event, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not regained their baseline health-related quality of life., Conclusions: This investigation provides the first longitudinal description of long-term mortality and clinically relevant, health-related quality of life morbidity among children encountering community-acquired septic shock. Although in-hospital mortality was 9%, 35% of survivors demonstrated significant, health-related quality of life deterioration from baseline that persisted at least 1 year following hospitalization for septic shock.

Objectives: A companion article reports the trajectory of long-term mortality and significant health-related quality of life disability among children encountering septic shock. In this article, the investigators examine critical illness factors associated with these adverse outcomes., Design: Prospective, cohort-outcome study, conducted 2013-2017., Setting: Twelve United States academic PICUs., Patients: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support., Interventions: Illness severity, organ dysfunction, and resource utilization data were collected during PICU admission. Change from baseline health-related quality of life at the month 3 follow-up was assessed by parent proxy-report employing the Pediatric Quality of Life Inventory or the Stein-Jessop Functional Status Scale., Measurements and Main Results: In univariable modeling, critical illness variables associated with death and/or persistent, serious health-related quality of life deterioration were candidates for multivariable modeling using Bayesian information criterion. The most clinically relevant multivariable models were selected among models with near-optimal statistical fit. Three months following septic shock, 346 of 389 subjects (88.9%) were alive and 43 of 389 had died (11.1%); 203 of 389 (52.2%) had completed paired health-related quality of life surveys. Pediatric Risk of Mortality, cumulative Pediatric Logistic Organ Dysfunction scores, PICU and hospital durations of stay, maximum and cumulative vasoactive-inotropic scores, duration of mechanical ventilation, need for renal replacement therapy, extracorporeal life support or cardiopulmonary resuscitation, and appearance of pathologic neurologic signs were associated with adverse outcomes in univariable models. In multivariable regression analysis (odds ratio [95% CI]), summation of daily Pediatric Logistic Organ Dysfunction scores, 1.01/per point (1.01-1.02), p < 0.001; highest vasoactive-inotropic score, 1.02/per point (1.00-1.04), p = 0.003; and any acute pathologic neurologic sign/event, 5.04 (2.15-12.01), p < 0.001 were independently associated with death or persistent, serious deterioration of health-related quality of life at month 3., Conclusions and Relevance: Biologically plausible factors related to sepsis-associated critical illness organ dysfunction and its treatment were associated with poor outcomes at month 3 follow-up among children encountering septic shock.

Aim: Recommendations for standardised communication to reduce chest compression (CC) pauses are lacking. We aimed to achieve consensus and evaluate feasibility and efficacy using standardised communication during cardiopulmonary resuscitation (CPR) events., Methods: Modified Delphi consensus process to design standardised communication elements. Feasibility was pilot tested in 16 simulated CPR scenarios (8 scenarios with physician team leaders and 8 with chest compressors) randomized (1:1) to standardised [INTERVENTION] vs. closed-loop communication [CONTROL]. Adherence and efficacy (duration of CC pauses for defibrillation, intubation, rhythm check) was assessed by audiovisual recording. Mental demand and frustration were assessed by NASA task load index subscales., Results: Consensus elements for standardised communication included: 1) team preparation 15-30 s before CC interruption, 2) pre-interruption countdown synchronized with last 5 CCs, 3) specific action words for defibrillation, intubation, and interrupting/resuming CCs. Median (Q1,Q3) adherence to standardised phrases was 98% (80%,100%). Efficacy analysis showed a median [Q1,Q3] peri-shock pause of 5.1 s. [4.4; 5.8] vs. 7.5 s. [6.3; 8.8] seconds, p < 0.001, intubation pause of 3.8 s. [3.6; 5.0] vs. 6.9 s. [4.8; 10.1] seconds, p = 0.03, rhythm check pause of 4.2 [3.2,5.7] vs. 8.6 [5.0,10.5] seconds, p < 0.001, median frustration index of 10/100 [5,20] vs. 35/100 [25,50], p < 0.001, and median mental demand load of 55/100 [30,70] vs. 65/100 [50,85], p = 0.41 for standardised vs. closed loop communication., Conclusion: This pilot study demonstrated feasibility of using consensus-based standardised communication that was associated with shorter CC pauses for defibrillation, intubation, and rhythm checks without increasing frustration index or mental demand compared to current best practice, closed loop communication., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: To evaluate the association of a single episode of hypotension and burden of hypotension with survival to hospital discharge following resuscitation from pediatric cardiac arrest., Design: Retrospective cohort study., Setting: Single-center PICU., Patients: Patients between 1 day and 18 years old who had a cardiac arrest, received chest compressions for more than 2 minutes, had return of spontaneous circulation for more than 20 minutes, and survived to receive postresuscitation care in the ICU., Interventions: None., Measurement and Main Results: One-hundred sixteen patients were evaluable. Hypotension, defined as systolic blood pressure less than the fifth percentile for age and sex, occurred in 37 patients (32%) within the first 6 hours and 64 (55%) within 72 hours of postresuscitation ICU care. There was no significant difference in survival to discharge for patients who had a single episode of hypotension within 6 hours (51% vs 69%; p = 0.06) or within 72 hours (56% vs 73%; p = 0.06). Burden of hypotension was defined as the percentage of hypotension measurements that were below the fifth percentile. After controlling for patient and cardiac arrest event characteristics, a higher burden of hypotension within the first 72 hours of ICU postresuscitation care was associated with decreased discharge survival (adjusted odds ratio = 0.67 per 10% increase in hypotension burden; 95% CI, 0.48-0.86; p = 0.006)., Conclusions: After successful resuscitation from pediatric cardiac arrest, systolic hypotension was common (55%). A higher burden of postresuscitation hypotension within the first 72 hours of ICU postresuscitation care was associated with significantly decreased discharge survival, after accounting for potential confounders including number of doses of epinephrine, arrest location, and arrest etiology due to airway obstruction or trauma.

Background and Objectives: Chart reviews are frequently used for research, care assessments, and quality improvement activities despite an absence of data on reliability and validity. We aim to describe a structured chart review methodology and to establish its validity and reliability., Methods: A generalizable structured chart review methodology was designed to evaluate causes of morbidity or mortality and to identify potential therapeutic advances. The review process consisted of a 2-tiered approach with a primary review completed by a site physician and a short secondary review completed by a central physician. A total of 327 randomly selected cases of known mortality or new morbidities were reviewed. Validity was assessed by using postreview surveys with a Likert scale. Reliability was assessed by percent agreement and interrater reliability., Results: The primary reviewers agreed or strongly agreed in 94.9% of reviews that the information to form a conclusion about pathophysiological processes and therapeutic advances could be adequately found. They agreed or strongly agreed in 93.2% of the reviews that conclusions were easy to make, and confidence in the process was 94.2%. Secondary reviewers made modifications to 36.6% of cases. Duplicate reviews ( n = 41) revealed excellent percent agreement for the causes (80.5%-100%) and therapeutic advances (68.3%-100%). κ statistics were strong for the pathophysiological categories but weaker for the therapeutic categories., Conclusions: A structured chart review by knowledgeable primary reviewers, followed by a brief secondary review, can be valid and reliable., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Importance: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial., Objective: To determine if the transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children., Design, Setting, and Participants: The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded., Interventions: Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group., Main Outcomes and Measures: The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death., Results: Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34)., Conclusions and Relevance: Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells., Trial Registration: ClinicalTrials.gov Identifier: NCT01977547.

Objectives: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis., Design: Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure., Setting: Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network., Patients: Children with severe sepsis and indwelling arterial or central venous catheters., Interventions: Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge., Measurements and Main Results: Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06-6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72-18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35-4.08)., Conclusions: These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children.

Objectives: To assess the association of diastolic blood pressure cutoffs (≥ 25 mm Hg in infants and ≥ 30 mm Hg in children) during cardiopulmonary resuscitation with return of spontaneous circulation and survival in surgical cardiac versus medical cardiac patients. Secondarily, we assessed whether these diastolic blood pressure targets were feasible to achieve and associated with outcome in physiology unique to congenital heart disease (single ventricle infants, open chest), and influenced outcomes when extracorporeal cardiopulmonary resuscitation was deployed., Design: Multicenter, prospective, observational cohort analysis., Setting: Tertiary PICU and cardiac ICUs within the Collaborative Pediatric Critical Care Research Network., Patients: Patients with invasive arterial catheters during cardiopulmonary resuscitation and surgical cardiac or medical cardiac illness category., Interventions: None., Measurements and Main Results: Hemodynamic waveforms during cardiopulmonary resuscitation were analyzed on 113 patients, 88 surgical cardiac and 25 medical cardiac. A similar percent of surgical cardiac (51/88; 58%) and medical cardiac (17/25; 68%) patients reached the diastolic blood pressure targets (p = 0.488). Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients (p = 0.018), but not medical cardiac patients (p = 0.359). Fifty-three percent (16/30) of patients with single ventricles attained the target diastolic blood pressure. In patients with an open chest at the start of chest compressions, 11 of 20 (55%) attained the target diastolic blood pressure. In the 33 extracorporeal cardiopulmonary resuscitation patients, 16 patients (48%) met the diastolic blood pressure target with no difference between survivors and nonsurvivors (p = 0.296)., Conclusions: During resuscitation in an ICU, with invasive monitoring in place, diastolic blood pressure targets of greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in children can be achieved in patients with both surgical and medical heart disease. Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients, but not medical cardiac patients. Diastolic blood pressure targets were feasible to achieve in 1) single ventricle patients, 2) open chest physiology, and 3) extracorporeal cardiopulmonary resuscitation patients.

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.

Utstein-style reporting templates provide a structured framework with which to compare systems of care for cardiac arrest. The 2004 Utstein reporting template encompassed both out-of-hospital and in-hospital cardiac arrest. A 2015 update of the Utstein template focused on out-of-hospital cardiac arrest, which makes this update of the in-hospital template timely. Representatives of the International Liaison Committee on Resuscitation developed an updated in-hospital Utstein reporting template iteratively by meeting face-to-face, by teleconference, and by online surveys between 2013 and 2018. Data elements were grouped by hospital factors, patient variables, pre-event factors, cardiac arrest and postresuscitation processes, and outcomes. Elements were classified as core or supplemental by use of a modified Delphi process. Variables were described as core if they were considered essential. Core variables should enable reasonable comparisons between systems and are considered essential for quality improvement programs. Together with core variables, supplementary variables are considered useful for research., (Copyright © 2019 European Resuscitation Council, American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.)

Aim: Diastolic blood pressure (DBP) during cardiopulmonary resuscitation (CPR) is associated with survival following pediatric in-hospital cardiac arrest. The relationship between intra-arrest haemodynamics and neurological status among survivors of pediatric cardiac arrest is unknown., Methods: This study represents analysis of data from the prospective multicenter Pediatric Intensive Care Quality of cardiopulmonary resuscitation (PICqCPR) Study. Primary predictor variables were median DBP and median systolic blood pressure (SBP) over the first 10min of CPR. The primary outcome measure was "new substantive morbidity" determined by Functional Status Scale (FSS) and defined as an increase in the FSS of at least 3 points or increase of 2 in a single FSS domain. Univariable analyses were completed to investigate the relationship between new substantive morbidity and BPs during CPR., Results: 244 index CPR events occurred during the study period, 77 (32%) CPR events met all inclusion criteria as well as having both DBP and FSS data available. Among 77 survivors, 32 (42%) had new substantive morbidity as measured by the FSS score. No significant differences were identified in DBP (median 30.5mmHg vs. 30.9mmHg, p=0.5) or SBP (median 76.3mmHg vs. 63.0mmHg, p=0.2) between patients with and without new substantive morbidity. Children who developed new substantive morbidity were more likely to have lower pre-arrest FSS than those that did not (median [IQR]: 7.5 [6.0-9.0] versus 9.0 [7.0-13.0], p=0.01)., Conclusion: New substantive morbidity determined by FSS after a pediatric IHCA was associated with baseline functional status, but not DBP during CPR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Thiamine deficiency may propagate lactate production by limiting pyruvate dehydrogenase activity, and studies suggest benefit for thiamine administration in septic adults. We studied the effect of thiamine on physiologic and clinical outcomes for children with septic shock and hyperlactatemia., Design: Retrospective matched cohort study., Setting: Single academic PICU., Patients: Six thiamine-treated cases and nine matched controls., Interventions: None., Measurements and Main Results: The primary outcome was change in blood lactate from prethiamine (T0, cases) or maximum (T0, controls) lactate through 24 hours later (T24). Secondary outcomes were change in lactate over 48 hours (T48) and 72 hours (T72), time to lactate normalization, changes in vasoactive-inotrope score, organ dysfunction severity (daily Pediatric Logistic Organ Dysfunction 2 score), and creatinine, PICU length of stay, and hospital mortality. Lactate was greater than 5 mmol/L for a median of 39 hours (range, 16.1-64.3 hr) prior to thiamine administration for cases compared with 3.4 hours (range, 0-22.9 hr) prior to maximum lactate for controls (p = 0.002). There was no difference in median (interquartile range) change in lactate from T0 to T24 between thiamine-treated cases and controls (-9.0, -17.0 to -5.0 vs -7.2, -9.0 to -5.3 mmol/L, p = 0.78), with both groups exhibiting a rapid decrease in lactate. There were also no differences in secondary outcomes between groups., Conclusions: Treatment of pediatric septic shock with thiamine was followed by rapid improvement in physiologic and clinical outcomes after prolonged hyperlactatemia. Although we are not able to infer that thiamine provided benefit over usual care, the rapid decline in lactate after thiamine despite a prolonged period of hyperlactatemia raises the possibility that thiamine helped to reverse lactate production.

Objectives: To evaluate the prevalence of do-not-resuscitate status, assess the epidemiologic trends of do-not-resuscitate status, and assess the factors associated with do-not-resuscitate status in children after in-hospital cardiac arrest using large, multi-institutional data., Design: Generalized estimating equations logistic regression model was used to evaluate the trends of do-not-resuscitate status and evaluate the factors associated with do-not-resuscitate status after cardiac arrest., Setting: American Heart Association's Get With the Guidelines-Resuscitation Registry., Patients: Children (< 18 yr old) with an index in-hospital cardiac arrest and greater than or equal to 1 minute of documented chest compressions were included (2006-2015). Patients with no return of spontaneous circulation after cardiac arrest were excluded., Interventions: None., Measurements and Main Results: In total, 8,062 patients qualified for inclusion. Of these, 1,160 patients (14.4%) adopted do-not-resuscitate status after cardiac arrest. We found low rates of survival to hospital discharge among children with do-not-resuscitate status (do-not-resuscitate vs no do-not-resuscitate: 6.0% vs 69.7%). Our study found that rates of do-not-resuscitate status after cardiac arrest are highest in children with Hispanic ethnicity (16.4%), white race (15.0%), and treatment at institutions with larger PICUs (> 50 PICU beds: 17.8%) and at institutions located in North Central (17.6%) and South Atlantic/Puerto Rico (17.1%) regions of the United States. Do-not-resuscitate status was more common among patients with more preexisting conditions, longer duration of cardiac arrest, greater than 1 cardiac arrest, and among patients requiring extracorporeal cardiopulmonary resuscitation. We also found that trends of do-not-resuscitate status after cardiac arrest in children are decreasing in recent years (2013-2015: 13.8%), compared with previous years (2006-2009: 16.0%)., Conclusions: Patient-, hospital-, and regional-level factors are associated with do-not-resuscitate status after pediatric cardiac arrest. As cardiac arrest might be a signal of terminal chronic illness, a timely discussion of do-not-resuscitate status after cardiac arrest might help families prioritize quality of end-of-life care.

Aim: In-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0-20 min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge., Methods: This is a secondary analysis of the Pediatric Intensive Care Quality of CPR (PICqCPR) study of invasively measured blood pressures during intensive care unit CPR. Patients were eligible if they achieved ROSC and had at least one invasively measured blood pressure within the first 20 min following ROSC. Post-ROSC blood pressures were normalized for age, sex and height. "Immediate hypertension" was defined as at least one systolic or diastolic blood pressure >90th percentile. The primary outcome was survival to hospital discharge., Results: Of 102 children, 70 (68.6%) had at least one episode of immediate post-CPR diastolic hypertension. After controlling for pre-existing hypotension, duration of CPR, calcium administration, and first documented rhythm, patients with immediate post-CPR diastolic hypertension were more likely to survive to hospital discharge (79.3% vs. 54.5%; adjusted OR = 2.93; 95%CI, 1.16-7.69)., Conclusions: In this post hoc secondary analysis of the PICqCPR study, 68.6% of subjects had diastolic hypertension within 20 min of ROSC. Immediate post-ROSC hypertension was associated with increased odds of survival to discharge, even after adjusting for covariates of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: Approximately 40% of children who have an in-hospital cardiac arrest (IHCA) in the US survive to discharge. We aimed to evaluate the impact of post-cardiac arrest hypotension during targeted temperature management following IHCA on survival to discharge., Methods: This is a secondary analysis of the therapeutic hypothermia after pediatric cardiac arrest in-hospital (THAPCA-IH) trial. "Early hypotension" was defined as a systolic blood pressure less than the fifth percentile for age and sex for patients not treated with extracorporeal membrane oxygenation (ECMO) or a mean arterial pressure less than fifth percentile for age and sex for patients treated with ECMO during the first 6 h of temperature intervention. The primary outcome was survival to hospital discharge., Results: Of 299 children, 142 (47%) patients did not receive ECMO and 157 (53%) received ECMO. Forty-two of 142 (29.6%) non-ECMO patients had systolic hypotension. Twenty-three of 157 (14.7%) ECMO patients had mean arterial hypotension. After controlling for confounders of interest, non-ECMO patients who had early systolic hypotension were less likely to survive to hospital discharge (40.5% vs. 72%; adjusted OR [aOR] 0.34; 95%CI, 0.12-0.93). There was no difference in survival to discharge by blood pressure groups for children treated with ECMO (30.4% vs. 49.3%; aOR = 0.60; 95%CI, 0.22-1.63)., Conclusions: In this secondary analysis of the THAPCA-IH trial, in patients not treated with ECMO, systolic hypotension within 6 h of temperature intervention was associated with lower odds of discharge survival. Blood pressure groups in patients treated with ECMO were not associated with survival to discharge., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cardiopulmonary resuscitation (CPR) is initiated in hospitalized children with bradycardia and poor perfusion. However, their rate of progression to pulseless cardiac arrest despite CPR and the differences in survival compared with initially pulseless arrest are unknown. We examined the prevalence and predictors of survival of children who progress from bradycardia to pulseless in-hospital cardiac arrest despite CPR., Methods: Pediatric patients >30 days and <18 years of age who received CPR at hospitals participating in Get With The Guidelines-Resuscitation during 2000 to 2016 were included. Each CPR event was classified as bradycardia with pulse, bradycardia with subsequent pulselessness, and initial pulseless cardiac arrest. We assessed risk-adjusted rates of survival to hospital discharge using multilevel Poisson regression models., Results: Overall, 5592 pediatric patients were treated with CPR, of whom 2799 (50.1%) received CPR for bradycardia with poor perfusion and 2793 (49.9%) for initial pulseless cardiac arrest. Among those with bradycardia, 869 (31.0%, or 15.5% of cohort) became pulseless after a median of 3 minutes of CPR (interquartile range, 1-9 minutes). Rates of survival to discharge were 70.0% (1351 of 1930) for bradycardia with pulse, 30.1% (262 of 869) for bradycardia progressing to pulselessness, and 37.5% (1046 of 2793) for initial pulseless cardiac arrest (P for difference across groups <0.001). Children who became pulseless despite CPR for bradycardia had a 19% lower likelihood (risk ratio, 0.81 [95% CI, 0.70, 0.93]; P=0.004) of surviving to hospital discharge than those who were initially pulseless. Among children who progressed to pulselessness despite CPR for bradycardia, a longer interval between CPR and pulselessness was a predictor of lower survival (reference, <2 minutes; for 2-5 minutes, risk ratio, 0.54 [95% CI, 0.41-0.70]; for >5 minutes, risk ratio, 0.41 [95% CI, 0.32-0.53])., Conclusions: Among hospitalized children in whom CPR is initiated, half have bradycardia with poor perfusion at the initiation of chest compressions, and nearly one-third of these progress to pulseless in-hospital cardiac arrest despite CPR. Survival was significantly lower for children who progress to pulselessness despite CPR compared with those who were initially pulseless. These findings suggest that pediatric patients who lose their pulse despite resuscitation attempts are at particularly high risk and require a renewed focus on postresuscitation care.

Background Whether racial and neighborhood characteristics are associated with bystander cardiopulmonary resuscitation ( BCPR ) in pediatric out-of-hospital cardiac arrest ( OHCA ) is unknown. Methods and Results An analysis was conducted of CARES (Cardiac Arrest Registry to Enhance Survival) for pediatric nontraumatic OHCA s from 2013 to 2017. An index (range, 0-4) was created for each arrest based on neighborhood characteristics associated with low BCPR (>80% black; >10% unemployment; <80% high school; median income, <$50 000). The primary outcome was BCPR . BCPR occurred in 3399 of 7086 OHCA s (48%). Compared with white children, BCPR was less likely in other races/ethnicities (black: adjusted odds ratio [ aOR ], 0.59; 95% CI , 0.52-0.68; Hispanic: aOR , 0.78; 95% CI , 0.66-0.94; and other: aOR , 0.54; 95% CI , 0.40-0.72). Compared with arrests in neighborhoods with an index score of 0, BCPR occurred less commonly for arrests with an index score of 1 ( aOR , 0.80; 95% CI , 0.70-0.91), 2 ( aOR , 0.75; 95% CI , 0.65-0.86), 3 ( aOR , 0.52; 95% CI , 0.45-0.61), and 4 ( aOR , 0.46; 95% CI , 0.36-0.59). Black children had an incrementally lower likelihood of BCPR with increasing index score while white children had an overall similar likelihood at most scores. Black children with an index of 4 were approximately half as likely to receive BCPR compared with white children with a score of 0. Conclusions Racial and neighborhood characteristics are associated with BCPR in pediatric OHCA . Targeted CPR training for nonwhite, low-education, and low-income neighborhoods may increase BCPR and improve pediatric OHCA outcomes.

In 2010, prompted by compelling evidence that demonstrated better patient outcomes in hospitals with higher percentages of nurses with a bachelor of science in nursing (BSN), the Institute of Medicine recommended that 80 percent of the nurse workforce be qualified at that level or higher by 2020. Using data from the American Heart Association's Get With the Guidelines-Resuscitation registry (for 2013-18), RN4CAST-US hospital nurse surveys (2015-16), and the American Hospital Association (2015), we found that each 10-percentage-point increase in the hospital share of nurses with a BSN was associated with 24 percent greater odds of surviving to discharge with good cerebral performance among patients who experienced in-hospital cardiac arrest. Lower patient-to-nurse ratios on general medical and surgical units were also associated with significantly greater odds of surviving with good cerebral performance. These findings contribute to the growing body of evidence that supports policies to increase access to baccalaureate-level education and improve hospital nurse staffing.

Out-of-hospital cardiac arrest (OHCA) remains a leading cause of death worldwide, with substantial geographical, ethnic and socioeconomic disparities in outcome. Successful resuscitation efforts depend on the 'chain of survival', which includes immediate recognition of cardiac arrest and activation of the emergency response system, early bystander cardiopulmonary resuscitation (CPR) with an emphasis on chest compressions, rapid defibrillation, basic and advanced emergency medical services and integrated post-cardiac arrest care. Well-orchestrated telecommunicator CPR programmes can improve rates of bystander CPR - a critical link in the chain of survival. High-performance CPR by emergency medical service providers includes minimizing interruptions in chest compressions and ensuring adequate depth of compressions. Developing local, regional and statewide systems with dedicated high-performing cardiac resuscitation centres for post-resuscitation care can substantially improve survival after OHCA. Innovative digital tools for recognizing cardiac arrest where and when it occurs, notifying potential citizen rescuers and providing automated external defibrillators at the scene hold the promise of improving survival after OHCA. Improved implementation of the chain of survival can save thousands of lives each year.

Objectives: Estimate the inter-rater reliability of critical care nurses performing a pediatric modification of the Glasgow Coma Scale in a contemporary PICU., Design: Prospective observation study., Setting: Large academic PICU., Patients/subjects: All 274 nurses with permanent assignments in the PICU were eligible to participate. A subset of 18 nurses were selected as study registered nurses. All PICU patients were eligible to participate., Interventions: None., Measurements and Main Results: PICU nurses were educated and demonstrated proficiency on a pediatric modification of the Glasgow Coma Scale we created to make it more applicable to a diverse PICU population that included patients who are sedated, mechanically ventilated, and/or have developmental disabilities. Each study registered nurse observed a sample of nurses perform the Glasgow Coma Scale, and they independently scored the Glasgow Coma Scale. Patients were categorized as having developmental disabilities if their preillness Pediatric Cerebral Performance Category score was greater than or equal to 3. Fleiss' Kappa (κ), intraclass correlation coefficient, and percent agreement assessed inter-rater reliability for each Glasgow Coma Scale component (eye, verbal, motor) and age-specific scale (≥ 2 and < 2-yr-old). The overall percent agreement between study registered nurses and nurses was 89% for the eye, 91% for the verbal, and 79% for the motor responses. Inter-rater reliability ranged from good (intraclass correlation coefficient = 0.75) to excellent (intraclass correlation coefficient = 0.96) for testable patients. Agreement on the motor response was significantly lower for children with developmental disabilities (< 2 yr: 59% vs 95%; p = 0.0012 and ≥ 2 yr: 55% vs 91%; p = 0.0012). Agreement was significantly worse for intermediate range Glasgow Coma Scale motor responses compared with responses at the extremes (e.g., motor responses 2, 3, 4 vs 1, 5, 6; p < 0.05)., Conclusions: A pediatric modification of the Glasgow Coma Scale performed by trained PICU nurses has excellent inter-rater reliability, although reliability was reduced in patients with developmental disabilities and for intermediate range Glasgow Coma Scale responses. Further research is needed to determine the effectiveness of this Glasgow Coma Scale modification to detect clinical deterioration.

Aim: Animal studies have established deleterious hemodynamic effects of interrupting chest compressions. The objective of this study was to evaluate the effect of interruptions on invasively measured blood pressures (BPs) during pediatric in-hospital cardiac arrest (IHCA)., Methods: This was a single-center, observational study of pediatric (<18 years) intensive care unit IHCAs in patients with invasive arterial catheters in place. Interruptions were defined as ≥1 s between chest compressions. Diastolic BP (DBP) and systolic BP (SBP) were determined for individual compressions. For the primary analysis, the average DBP and SBP of the 20 compressions preceding each interruption were compared to the average DBP and SBP of the first 20 compressions following each interruption utilizing non-parametric paired analyses. Linear regression evaluated the change in DBP during interruptions and following interruptions., Results: Thirty-two IHCA events met inclusion criteria, yielding 161 evaluable interruptions. The median age was 2.1 years. Return of circulation was achieved in 24 (75%). The median interruption duration was 2.4 [1.4, 7.0] seconds. Most patients were intubated pre-arrest and received epinephrine during CPR. BPs were not different pre- vs. post-interruption (DBP: 28.7 [21.6, 38.2] vs. 28.3 [21.0, 37.4] mmHg, p = 0.81; SBP: 82.0 [51.7, 116.7] vs. 85.4 [55.7, 122.2] mmHg, p = 0.07). DBP decreased 8.41 ± 0.73 mmHg (p < 0.001) during the first second of interruptions and 0.19 ± 0.02 mmHg/s (p < 0.001) in subsequent seconds., Conclusions: BPs following chest compression interruptions did not differ from pre-interruption BPs. These findings suggest that in the setting of high-quality in-hospital CPR, brief chest compression interruptions do not have persistent detrimental hemodynamic impact., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Systems vaccinology approaches have been used successfully to define early signatures of the vaccine-induced immune response. However, the possibility that transcriptomics can also identify a correlate or surrogate for vaccine inflammation has not been fully explored. We have compared four licensed vaccines with known safety profiles, as well as three agonists of Toll-like receptors (TLRs) with known inflammatory potential, to elucidate the transcriptomic profile of an acceptable response to vaccination versus that of an inflammatory reaction. In mice, we looked at the transcriptomic changes in muscle at the injection site, the lymph node that drained the muscle, and the peripheral blood mononuclear cells (PBMCs)isolated from the circulating blood from 4 hr after injection and over the next week. A detailed examination and comparative analysis of these transcriptomes revealed a set of novel biomarkers that are reflective of inflammation after vaccination. These biomarkers are readily measurable in the peripheral blood, providing useful surrogates of inflammation, and provide a way to select candidates with acceptable safety profiles., Competing Interests: PM, DC, YA, JM, JW, SK, DL, RS No competing interests declared, Rv, GD is an employee of the GSK group of companies. Reports ownership of shares and/or restricted shares in GSK, (© 2019, McKay et al.)

Importance: Guidelines for declaration of brain death in children were revised in 2011 by the Society of Critical Care Medicine, American Academy of Pediatrics, and Child Neurology Society. Despite widespread medical, legal, and ethical acceptance, ongoing controversies exist with regard to the concept of brain death and the procedures for its determination., Objectives: To determine the epidemiology and clinical characteristics of pediatric patients declared brain dead in the United States., Design, Setting, and Participants: This study involved the abstraction of all patient deaths from the Virtual Pediatric Systems national multicenter database between January 1, 2012, and June 30, 2017. All patients who died in pediatric intensive care units (PICUs) were included., Main Outcomes and Measures: Patient demographics, preillness developmental status, severity of illness, cause of death, PICU medical and physical length of stay, and organ donation status, as well as comparison between patients who were declared brain dead vs those who sustained cardiovascular or cardiopulmonary death., Results: Of the 15 344 patients who died, 3170 (20.7%) were declared brain dead; 1861 of these patients (58.7%) were male, and 1401 (44.2%) were between 2 and 12 years of age. There was a linear association between PICU size and number of patients declared brain dead per year, with an increase of 4.27 patients (95% CI, 3.46-5.08) per 1000-patient increase in discharges (P < .001). The median (interquartile range) of patients declared brain dead per year ranged from 1 (0-3) in smaller PICUs (defined as those with <500 discharges per year) to 10 (7-15) for larger PICUs (those with 2000-4000 discharges per year). The most common causative mechanisms of brain death were hypoxic-ischemic injury owing to cardiac arrest (1672 of 3170 [52.7%]), shock and/or respiratory arrest without cardiac arrest (399 of 3170 [12.6%]), and traumatic brain injury (634 of 3170 [20.0%]). Most patients declared brain dead (681 of 807 [84.4%]) did not have preexisting neurological dysfunction. Patients who were organ donors (1568 of 3144 [49.9%]) remained in the PICU longer after declaration of brain death compared with those who were not donors (median [interquartile range], 29 [6-41] hours vs 4 [1-8] hours; P < .001)., Conclusions and Relevance: Brain death occurred in one-fifth of PICU deaths. Most children declared brain dead had no preexisting neurological dysfunction and had an acute hypoxic-ischemic or traumatic brain injury. Brain death determinations are infrequent, even in large PICUs, emphasizing the importance of ongoing education for medical professionals and standardization of protocols to ensure diagnostic accuracy and consistency.

Objectives: Children with dependence on respiratory or feeding technologies are frequently admitted to the PICU, but little is known about their characteristics or outcomes. We hypothesized that they are at increased risk of critical illness-related morbidity and mortality compared with children without technology dependence., Design: Secondary analysis of prospective, probability-sampled cohort study of children from birth to 18 years old. Demographic and clinical characteristics were assessed. Outcomes included death, survival with new morbidity, intact survival, and survival with functional status improvement., Setting: General and cardiovascular PICUs at seven participating children's hospitals as part of the Trichotomous Outcome Prediction in Critical Care study., Subjects: Children from birth to 18 years of age as part of the Trichotomous Outcome Prediction in Critical Care study., Interventions: None., Measurements and Main Results: Children with technology dependence composed 19.7% (1,989/10,078) of PICU admissions. Compared with those without these forms of technology dependence, these children were younger, received more ICU-specific therapeutics, and were more frequently readmitted to the ICU. Death occurred in 3.7% of technology-dependent patients (n = 74), and new morbidities developed in 4.5% (n = 89). Technology-dependent children who developed new morbidities had higher Pediatric Risk of Mortality scores and received more ICU therapies than those who did not. A total of 3.0% of technology-dependent survivors (n = 57) showed improved functional status at hospital discharge., Conclusions: Children with feeding and respiratory technology dependence composed approximately 20% of PICU admissions. Their new morbidity rates are similar to those without technology dependence, which contradicts our hypothesis that children with technology dependence would demonstrate worse outcomes. These comparable outcomes, however, were achieved with additional resources, including the use of more ICU therapies and longer lengths of stay. Improvement in functional status was seen in some technology-dependent survivors of critical illness.

Objectives: To develop a prognostic model for predicting mortality at time of extracorporeal membrane oxygenation initiation for children which is important for determining center-specific risk-adjusted outcomes., Design: Multivariable logistic regression using a large national cohort of pediatric extracorporeal membrane oxygenation patients., Setting: The ICUs of the eight tertiary care children's hospitals of the Collaborative Pediatric Critical Care Research Network., Patients: Five-hundred fourteen children (< 19 yr old), enrolled with an initial extracorporeal membrane oxygenation run for any indication between January 2012 and September 2014., Interventions: None., Measurements and Main Results: A total of 514 first extracorporeal membrane oxygenation runs were analyzed with an overall mortality of 45% (n = 232). Weighted logistic regression was used for model selection and internal validation was performed using cross validation. The variables included in the Pediatric Extracorporeal Membrane Oxygenation Prediction model were age (pre-term neonate, full-term neonate, infant, child, and adolescent), indication for extracorporeal membrane oxygenation (extracorporeal cardiopulmonary resuscitation, cardiac, or respiratory), meconium aspiration, congenital diaphragmatic hernia, documented blood stream infection, arterial blood pH, partial thromboplastin time, and international normalized ratio. The highest risk of mortality was associated with the presence of a documented blood stream infection (odds ratio, 5.26; CI, 1.90-14.57) followed by extracorporeal cardiopulmonary resuscitation (odds ratio, 4.36; CI, 2.23-8.51). The C-statistic was 0.75 (95% CI, 0.70-0.80)., Conclusions: The Pediatric Extracorporeal Membrane Oxygenation Prediction model represents a model for predicting in-hospital mortality among children receiving extracorporeal membrane oxygenation support for any indication. Consequently, it holds promise as the first comprehensive pediatric extracorporeal membrane oxygenation risk stratification model which is important for benchmarking extracorporeal membrane oxygenation outcomes across many centers.

Objectives: To evaluate the variation of hospital rates of delayed epinephrine administration in pediatric patients with nonshockable in-hospital cardiac arrest, and the association of those rates with event, 24-hour, and overall survival to hospital discharge., Design: A retrospective evaluation was performed. Delayed epinephrine was defined as greater than 5 minutes between the time the need for chest compressions was identified and epinephrine was administered. The main outcome was the association of hospital rate of delayed epinephrine administration with survival to hospital discharge. Secondary outcomes were event and 24-hour survival. Evaluation used hierarchical logistic regression and included 13 patient/event-level and seven hospital-level factors., Setting: Hospitals with greater than 6 months data in the American Heart Association's Get With the Guidelines-Resuscitation registry (2000-2016) and greater than or equal to five total pediatric cardiac arrests with nonshockable rhythm., Patients: Children less than 18 years old with index nonshockable in-hospital cardiac arrest treated with greater than or equal to one epinephrine dose., Interventions: None., Measurements and Main Results: One-thousand four-hundred sixty-two patients at 69 hospitals were included: 218 patients (14.9%) had epinephrine delay rates ranging from 0% to 80% of events (median, 15.6%; interquartile range, 7-25%). The median and interquartile range of hospital level delay was 16% (7-25%). Patient/event-level predictors of delayed epinephrine were asystole (odds ratio, 1.54 [95% CI, 1.10-2.16]) and insertion of an endotracheal tube (odds ratio, 1.86 [95% CI, 1.27-2.73]). Hospital size less than 200 compared with greater than or equal to 500 beds (odds ratio, 3.07 [95% CI, 1.22-7.73]) and ICU location (odds ratio, 0.51 [95% CI, 0.36-0.74]) were associated with epinephrine delay rates. After adjustment, increasing quartiles of epinephrine delay were associated with lower patient and hospital-level return of spontaneous circulation (p = 0.019, p = 0.006) and 24-hour survival (p = 0.018, p = 0.002) respectively, but not survival to discharge (p = 0.20, p = 0.24)., Conclusions: Delayed epinephrine administration following pediatric nonshockable in-hospital cardiac arrest varies significantly between hospitals. Hospitals with higher rates of delayed epinephrine administration had worse patient- and hospital-level outcomes after adjusting for multiple patient- and hospital-level factors. Delayed epinephrine administration may directly contribute to increased mortality risk and/or may be a marker of unmeasured elements of hospital resuscitation performance.

Background: Because pediatric trauma-related mortality continues to decline, metrics assessing morbidity are needed to evaluate the impact of treatment after injury. Based on its value for assessing children with traumatic brain injuries and other critical illnesses, Functional Status Scale (FSS), a tool that measures function in six domains (communication, feeding, mental, motor, sensory, and respiratory), was evaluated as an outcome measure for the overall population of injured children., Methods: Children with at least one injury (Abbreviated Injury Scale [AIS] severity ≥1) surviving to discharge between December 2011 and April 2013 were identified in a previous study of intensive care unit admissions. Morbidity was defined as additional morbidity in any domain (domain FSS change ≥2 or 'new domain morbidity') and additional overall morbidity (total FSS change ≥3) between preinjury status and discharge. Associations between injury profiles and the development of morbidity were analyzed., Results: We identified 553 injured children, with a mean of 2.0 ± 1.9 injuries. New domain and overall morbidity were observed in 17.0% and 11.0% of patients, respectively. New domain morbidity was associated with an increasing number of body regions with an injury with AIS ≥ 2 (p < 0.001), with severe (AIS ≥ 4) head (p = 0.04) and spine (p = 0.01) injuries and with at moderately severe (AIS ≥ 2) lower extremity injuries (p = 0.01). New domain morbidity was more common among patients with severe spine and lower extremity injuries (55.6% and 48.7%, respectively), with greatest impact in the motor domain (55.6% and 43.6%, respectively). New domain morbidity was associated with increasing injury severity score, number of moderately severe injuries and number of body regions with more than a moderately severe injury (p < 0.001 for all)., Conclusions: Higher morbidity measured by the FSS is associated with increasing injury severity. These findings support the use of the FSS as a metric for assessing outcome after pediatric injury., Level of Evidence: Prognostic/Epidemiologic, level III.

Objectives: Less than half of the thousands of children who suffer in-hospital cardiac arrests annually survive, and neurologic injury is common among survivors. Hemodynamic-directed cardiopulmonary resuscitation improves short-term survival, but its impact on longer term survival and mitochondrial respiration-a potential neurotherapeutic target-remains unknown. The primary objectives of this study were to compare rates of 24-hour survival with favorable neurologic outcome after cardiac arrest treated with hemodynamic-directed cardiopulmonary resuscitation versus standard depth-guided cardiopulmonary resuscitation and to compare brain and heart mitochondrial respiration between groups 24 hours after resuscitation., Design: Randomized preclinical large animal trial., Setting: A large animal resuscitation laboratory at a large academic children's hospital., Subjects: Twenty-eight 4-week-old female piglets (8-11 kg)., Interventions: Twenty-two swine underwent 7 minutes of asphyxia followed by ventricular fibrillation and randomized treatment with either hemodynamic-directed cardiopulmonary resuscitation (n = 10; compression depth titrated to aortic systolic pressure of 90 mm Hg, vasopressors titrated to coronary perfusion pressure ≥ 20 mm Hg) or depth-guided cardiopulmonary resuscitation (n = 12; depth 1/3 chest diameter, epinephrine every 4 min). Six animals (sham group) underwent anesthesia and instrumentation without cardiac arrest. The primary outcomes were favorable neurologic outcome (swine Cerebral Performance Category ≤ 2) and mitochondrial maximal oxidative phosphorylation utilizing substrate for complex I and complex II (OXPHOSCI+CII) in the cerebral cortex and hippocampus., Measurements and Main Results: Favorable neurologic outcome was more likely with hemodynamic-directed cardiopulmonary resuscitation (7/10) than depth-guided cardiopulmonary resuscitation (1/12; p = 0.006). Hemodynamic-directed cardiopulmonary resuscitation resulted in higher intra-arrest coronary perfusion pressure, aortic pressures, and brain tissue oxygenation. Hemodynamic-directed cardiopulmonary resuscitation resulted in higher OXPHOSCI+CII (pmol oxygen/s × mg/citrate synthase) in the cortex (6.00 ± 0.28 vs 3.88 ± 0.43; p < 0.05) and hippocampus (6.26 ± 0.67 vs 3.55 ± 0.65; p < 0.05) and higher complex I respiration (pmol oxygen/s × mg) in the right (20.62 ± 1.06 vs 15.88 ± 0.81; p < 0.05) and left ventricles (20.14 ± 1.40 vs 14.17 ± 1.53; p < 0.05)., Conclusions: In a model of asphyxia-associated pediatric cardiac arrest, hemodynamic-directed cardiopulmonary resuscitation increases rates of 24-hour survival with favorable neurologic outcome, intra-arrest hemodynamics, and cerebral and myocardial mitochondrial respiration.

During paediatric cardiopulmonary resuscitation (CPR), patients may transition between pulseless electrical activity (PEA), asystole, ventricular fibrillation/tachycardia (VF/VT), and return of spontaneous circulation (ROSC). The aim of this study was to quantify the dynamic characteristics of this process., Methods: ECG recordings were collected in patients who received CPR at the Children's Hospital of Philadelphia (CHOP) between 2006 and 2013. Transitions between PEA (including bradycardia with poor perfusion), VF/VT, asystole, and ROSC were quantified by applying a multi-state statistical model with competing risks, and by smoothing the Nelson-Aalen estimator of cumulative hazard., Results: Seventy-four episodes of cardiac arrest were included. Median age of patients was 15 years [IQR 11-17], 50% were female and 62% had a respiratory aetiology of arrest. Presenting cardiac arrest rhythms were PEA (60%), VF/VT (24%) and asystole (16%). A temporary surge of PEA was observed between 10 and 15 min due to a doubling of the transition rate from ROSC to PEA (i.e. 're-arrests'). The prevalence of sustained ROSC reached an asymptotic value of 30% at 20 min. Simulation suggests that doubling the transition rate from PEA to ROSC and halving the relapse rate might increase the prevalence of sustained ROSC to 50%., Conclusion: Children and adolescents who received CPR were prone to re-arrest between 10 and 15 min after start of CPR efforts. If the rate of PEA to ROSC transition could be increased and the rate of re-arrests reduced, the overall survival rate may improve., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Limited data exist on the effects of extracorporeal membrane oxygenation on pharmacokinetics of cefepime in critically ill pediatric patients. The objective was to describe cefepime disposition in children treated with extracorporeal membrane oxygenation using population pharmacokinetic modeling., Design: Multicenter, prospective observational study., Setting: The pediatric and cardiac ICUs of six sites of the Collaborative Pediatric Critical Care Research Network., Patients: Seventeen critically ill children (30 d to < 2 yr old) on extracorporeal membrane oxygenation who received cefepime as standard of care between January 4, 2014, and August 24, 2015, were enrolled., Interventions: None., Measurements and Main Results: A pharmacokinetic model was developed to evaluate cefepime disposition differences due to extracorporeal membrane oxygenation. A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data. The typical value of clearance in this study was 7.1 mL/min (1.9 mL/min/kg) for a patient weighing 5.8 kg. This value decreased by approximately 40% with the addition of renal replacement therapy. The typical value for V1 was 1,170 mL. In the setting of blood transfusions, V1 increased by over two-fold but was reduced with increasing age of the extracorporeal membrane oxygenation circuit oxygenator., Conclusions: Cefepime clearance was reduced in pediatric patients treated with extracorporeal membrane oxygenation compared with previously reported values in children not receiving extracorporeal membrane oxygenation. The model demonstrated that the age of the extracorporeal membrane oxygenation circuit oxygenator is inversely correlated to V1. For free cefepime, only 14 of the 19 doses (74%) demonstrated a fT&#95;minimum inhibitory concentration of 16 mg/L, an appropriate target for the treatment of pseudomonal infections, for greater than 70% of the dosing interval. Pediatric patients on extracorporeal membrane oxygenation might benefit from the addition of therapeutic drug monitoring of cefepime to assure appropriate dosing.

Objectives: Autopsy rates in North American Children's hospitals have not been recently evaluated. Our objectives were 1) to determine the autopsy rates from patients cared for in PICUs during a portion of their hospital stay, 2) to identify patient characteristics associated with autopsies, and 3) to understand the relative role of medical examiner cases., Design: Secondary analysis of data prospectively collected from a sample of patients (n = 10,078) admitted to PICUs affiliated with the Collaborative Pediatric Critical Care Research Network between December 2011 and April 2013., Setting: Eight quaternary care PICUs., Patients: Patients in the primary study were less than 18 years old, admitted to a PICU and not moribund on PICU admission. Patients included in this analysis were those who died during their hospital stay., Interventions: None., Measurements and Main Results: Sociodemographic, clinical, hospital, and PICU data were compared between patients who had autopsies conducted and those who did not and between medical examiner and nonmedical examiner autopsies. Of 10,078 patients, 275 died of which 36% (n = 100) had an autopsy performed. Patients with cancer who died were less likely to receive autopsies (p = 0.005), whereas those who died after trauma or cardiac arrest had autopsies performed more often (p < 0.01). Autopsies were more common in patients with greater physiologic instability at admission (p < 0.001), and those who received more aggressive PICU care. Medical examiner cases comprised nearly half of all autopsies (n = 47; 47%) were conducted in patients presenting with greater physiologic instability (p < 0.001) and more commonly after catastrophic events such as cardiac arrest or trauma (p < 0.001)., Conclusions: In this first multicenter analysis of autopsy rates in children, 36% of deaths had autopsies conducted, of which nearly half were conducted by the medical examiner. Deaths with autopsy are more likely to be previously healthy children that had catastrophic events prior to admission.

IntroductionNeurodevelopmental disabilities in children with CHD can result from neurologic injury sustained in the cardiac ICU when children are at high risk of acute neurologic injury. Physicians typically order and specify frequency for serial bedside nursing clinical neurologic assessments to evaluate patients' neurologic status.Materials and methodsWe surveyed cardiac ICU physicians to understand how these assessments are performed, and the attitudes of physicians on the utility of these assessments. The survey contained questions regarding assessment elements, assessment frequency, communication of neurologic status changes, and optimisation of assessments. RESULTS: Surveys were received from 50 institutions, with a response rate of 86%. Routine clinical neurologic assessments were reported to be performed in 94% of institutions and standardised in 56%. Pupillary reflex was the most commonly reported assessment. In all, 77% of institutions used a coma scale, with Glasgow Coma Scale being most common. For patients with acute brain injury, 82% of institutions reported performing assessments hourly, whereas assessment frequency was more variable for low-risk and high-risk patients without overt brain injury. In all, 84% of respondents thought their current practice for assessing and monitoring neurologic status was suboptimal. Only 41% felt that the Glasgow Coma Scale was a valuable tool for assessing neurologic function in the cardiac ICU, and 91% felt that a standardised approach to assessing pre-illness neurologic function would be valuable. CONCLUSIONS: Routine nursing neurologic assessments are conducted in most surveyed paediatric cardiac ICUs, although assessment characteristics vary greatly between institutions. Most clinicians rated current neurologic assessment practices as suboptimal.

Background: Early identification of children at risk for cardiac arrest would allow for skill training associated with improved outcomes and provides a prevention opportunity., Objective: Develop and assess a predictive model for cardiopulmonary arrest using data available in the first 4 h., Methods: Data from PICU patients from 8 institutions included descriptive, severity of illness, cardiac arrest, and outcomes., Results: Of the 10074 patients, 120 satisfying inclusion criteria sustained a cardiac arrest and 67 (55.9%) died. In univariate analysis, patients with cardiac arrest prior to admission were over 6 times and those with cardiac arrests during the first 4 h were over 50 times more likely to have a subsequent arrest. The multivariate logistic regression model performance was excellent (area under the ROC curve = 0.85 and Hosmer-Lemeshow statistic, p = 0.35). The variables with the highest odds ratio's for sustaining a cardiac arrest in the multivariable model were admission from an inpatient unit (8.23 (CI: 4.35-15.54)), and cardiac arrest in the first 4 h (6.48 (CI: 2.07-20.36). The average risk predicted by the model was highest (11.6%) among children sustaining an arrest during hours >4-12 and continued to be high even for days after the risk assessment period; the average predicted risk was 9.5% for arrests that occurred after 8 PICU days., Conclusions: Patients at high risk of cardiac arrest can be identified with routinely available data after 4 h. The cardiac arrest may occur relatively close to the risk assessment period or days later., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Based on laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data, the American Heart Association Consensus Statement on CPR Quality recommends titrating CPR performance to achieve end-tidal carbon dioxide (ETCO2) >20 mmHg., Aims: We prospectively evaluated whether ETCO2 > 20 mmHg during CPR was associated with survival to hospital discharge., Methods: Children ≥37 weeks gestation in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for ≥1 min and ETCO2 monitoring prior to and during CPR between July 1, 2013 and June 31, 2016 were included. ETCO2 and Utstein-style cardiac arrest data were collected. Multivariable Poisson regression models with robust error estimates were used to estimate relative risk of outcomes., Results: Blinded investigators analyzed ETCO2 waveforms from 43 children. During CPR, the median ETCO2 was 23 mmHg [quartiles, 16 and 28 mmHg], median ventilation rate was 29 breaths/min [quartiles, 24 and 35 breaths/min], and median duration of CPR was 5 min [quartiles, 2 and 16 min]. Return of spontaneous circulation occurred after 71% of CPR events and 37% of patients survived to hospital discharge. For children with mean ETCO2 during CPR > 20 mmHg, the adjusted relative risk for survival was 0.92 (0.41, 2.08), p = 0.84. The median mean ETCO2 among children who survived to hospital discharge was 20 mmHg [quartiles; 15, 28 mmHg] versus 23 mmHg [16, 28 mmHg] among non-survivors., Conclusion: Mean ETCO2 > 20 mmHg during pediatric in-hospital CPR was not associated with survival to hospital discharge, and ETCO2 was not different in survivors versus non-survivors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The quality of cardiopulmonary resuscitation (CPR) has been shown to impact patient outcomes. However, post-CPR morbidity and mortality remain high, and CPR optimization is an area of active research. One approach to optimizing CPR involves establishing reliable CPR performance measures and then modifying CPR parameters, such as compressions and ventilator breaths, to enhance these measures. We aimed to define a reliable CPR performance measure, optimize the CPR performance based on the defined measure and design a dynamically optimized scheme that varies CPR parameters to optimize CPR performance., Materials and Methods: We selected total blood gas delivery (systemic oxygen delivery and carbon dioxide delivery to the lungs) as an objective function for maximization. CPR parameters were divided into three categories: rescuer dependent, patient dependent, and constant parameters. Two optimization schemes were developed using simulated annealing method: a global optimization scheme and a sequential optimization scheme., Results and Discussion: Variations of CPR parameters over CPR sequences (cycles) were analyzed. Across all patient groups, the sequential optimization scheme resulted in significant enhancement in the effectiveness of the CPR procedure when compared to the global optimization scheme., Conclusions: Our study illustrates the potential benefit of considering dynamic changes in rescuer-dependent parameters during CPR in order to improve performance. The advantage of the sequential optimization technique stemmed from its dynamically adapting effect. Our CPR optimization findings suggest that as CPR progresses, the compression to ventilation ratio should decrease, and the sequential optimization technique can potentially improve CPR performance. Validation in vivo is needed before implementing these changes in actual practice.

Objectives: To describe factors associated with hemolysis during pediatric extracorporeal membrane oxygenation and the relationships between hemolysis, complications, and mortality., Design: Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014., Setting: Three Collaborative Pediatric Critical Care Research Network-affiliated hospitals., Patients: Age less than 19 years and treated with extracorporeal membrane oxygenation., Interventions: None., Measurements and Main Results: Hemolysis was defined based on peak plasma free hemoglobin levels during extracorporeal membrane oxygenation and categorized as none (< 0.001 g/L), mild (0.001 to < 0.5 g/L), moderate (0.5 to < 1.0 g/L), or severe (≥ 1.0 g/L). Of 216 patients, four (1.9%) had no hemolysis, 67 (31.0%) had mild, 51 (23.6%) had moderate, and 94 (43.5%) had severe. On multivariable analysis, variables independently associated with higher daily plasma free hemoglobin concentration included the use of in-line hemofiltration or other continuous renal replacement therapy, higher hemoglobin concentration, higher total bilirubin concentration, lower mean heparin infusion dose, lower body weight, and lower platelet count. Using multivariable Cox modeling, daily plasma free hemoglobin was independently associated with development of renal failure during extracorporeal membrane oxygenation (defined as creatinine > 2 mg/dL [> 176.8 μmol/L] or use of in-line hemofiltration or continuous renal replacement therapy) (hazard ratio, 1.04; 95% CI, 1.02-1.06; p < 0.001), but not mortality (hazard ratio, 1.01; 95% CI, 0.99-1.04; p = 0.389)., Conclusions: Hemolysis is common during pediatric extracorporeal membrane oxygenation. Hemolysis may contribute to the development of renal failure, and therapies used to manage renal failure such as in-line hemofiltration and other forms of continuous renal replacement therapy may contribute to hemolysis. Hemolysis was not associated with mortality after controlling for other factors. Monitoring for hemolysis should be a routine part of extracorporeal membrane oxygenation practice, and efforts to reduce hemolysis may improve patient care.

Background: Chest compression (CC) research primarily focuses on finding the 'optimum' compression waveform using a variety of compression efficacy metrics. Blood flow is rarely measured systematically with high fidelity. Using a programmable mechanical chest compression device, we studied the effect of inter-compression pauses in a swine model of cardiac arrest, testing the hypothesis that a single 'optimal' CC waveform exists based on measurements of resulting blood flow., Methods: Hemodynamics were studied in 9 domestic swine (∼30 kg) using multiple flow probes and standard physiological monitoring. After 10 min of ventricular fibrillation, five mechanical chest compression waveforms (5.1 cm, varying inter-compression pauses) were delivered for 2 min each in a semi-random pattern, totaling 50 compression minutes. Linear Mixed Models were used to estimate the effect of compression waveform on hemodynamics., Results: Blood flow and pressure decayed significantly with time in both arteries and veins. No waveform maximized blood flow in all vessels simultaneously and the waveform generating maximal blood flow in a specific vessel changed over time in all vessels. A flow mismatch between paired arteries and veins, e.g. abdominal aorta and inferior vena cava, also developed over time. The waveform with the slowest rate and shortest duty cycle had the smallest mismatch between flows after about 30 min of CPR., Conclusions: This data challenges the concept of a single optimal CC waveform. Time dependent physiological response to compressions and no single compression waveform optimizing flow in all vessels indicate that current descriptions of CPR don't reflect patient physiology., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Importance: Delayed defibrillation (>2 minutes) in adult in-hospital cardiac arrest (IHCA) is associated with worse outcomes. Little is known about the timing and outcomes of defibrillation in pediatric IHCA., Objective: To determine whether time to first defibrillation attempt in pediatric IHCA with a first documented shockable rhythm is associated with survival to hospital discharge., Design, Setting, and Participants: In this cohort study, data were obtained from the Get With The Guidelines-Resuscitation national registry between January 1, 2000, and December 31, 2015, and analyses were completed by October 1, 2017. Participants were pediatric patients younger than 18 years with an IHCA and a first documented rhythm of pulseless ventricular tachycardia or ventricular fibrillation and at least 1 defibrillation attempt., Exposures: Time between loss of pulse and first defibrillation attempt., Main Outcomes and Measures: The primary outcome was survival to hospital discharge. Secondary outcomes were return of circulation, 24-hour survival, and favorable neurologic outcome at hospital discharge., Results: Among 477 patients with a pulseless shockable rhythm (median [interquartile range] age, 4 years [3 months to 14 years]; 285 [60%] male), 338 (71%) had a first defibrillation attempt at 2 minutes or less after pulselessness. Children were less likely to be shocked in 2 minutes or less for ward vs intensive care unit IHCAs (48% [11 of 23] vs 72% [268 of 371]; P = .01]). Thirty-eight percent (179 patients) survived to hospital discharge. The median (interquartile range) reported time to first defibrillation attempt was 1 minute (0-3 minutes) in both survivors and nonsurvivors. Time to first defibrillation attempt was not associated with survival in unadjusted analysis (risk ratio [RR] per minute increase, 0.96; 95% CI, 0.92-1.01; P = .15) or adjusted analysis (RR, 0.99; 95% CI, 0.94-1.06; P = .86). There was no difference in survival between those with a first defibrillation attempt in 2 minutes or less vs more than 2 minutes in unadjusted analysis (132 of 338 [39%] vs 47 of 139 [34%]; RR, 0.87; 95% CI, 0.66-1.13; P = .29) or multivariable analysis (RR, 0.99; 95% CI, 0.75-1.30; P = .93). Time to first defibrillation attempt was also not associated with secondary outcome measures., Conclusions and Relevance: In contrast to published adult IHCA and pediatric out-of-hospital cardiac arrest data, no significant association was observed between time to first defibrillation attempt in pediatric IHCA with a first documented shockable rhythm and survival to hospital discharge.

Introduction: Our objectives are to (1) describe the pathogens, site, timing and risk factors for acquired infection during neonatal and pediatric ECMO and (2) explore the association between acquired infection and mortality., Methods: Secondary analysis of prospective data collected by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014. Clinical factors associated with acquired infection were assessed with multivariable Cox regression. Factors associated with mortality were assessed with logistic regression., Results: Of 481 patients, 247 (51.3%) were neonates and 400 (83.2%) received venoarterial ECMO. Eighty (16.6%) patients acquired one or more infections during ECMO; 60 (12.5%) patients had bacterial, 21 (4.4%) had fungal and 11 (2.3%) had viral infections. The site of infection included respiratory for 53 (11.0%) patients, bloodstream for 21 (4.4%), urine for 20 (4.2%) and other for 7 (1.5%). Candida species were most common. Median time to infection was 5.2 days (IQR 2.3, 9.6). On multivariable analysis, a greater number of procedures for ECMO cannula placement was independently associated with increased risk of acquired infection during ECMO (Hazard Ratio 2.13 (95% CI 1.22, 3.72), p<0.01) and receiving ECMO in a neonatal ICU compared to a pediatric or cardiac ICU was associated with decreased risk (Hazard Ratio pediatric ICU 4.25 (95% CI 2.20, 8.20), cardiac ICU 2.91 (95% CI 1.48, 5.71), neonatal ICU as reference, p<0.001). Acquired infection was not independently associated with mortality., Conclusion: ECMO procedures and location may contribute to acquired infection risk; however, acquired infection did not predict mortality in this study.

Aim: The primary aim of this study was to evaluate the association between chest compression rates and 1) arterial blood pressure and 2) survival outcomes during pediatric in-hospital cardiopulmonary resuscitation (CPR)., Methods: Prospective observational study of children ≥37 weeks gestation and <19 years old who received CPR in an intensive care unit (ICU) as part of the Pediatric Intensive Care Unit Quality of CPR Study (PICqCPR) of the Collaborative Pediatric Critical Care Research Network (CPCCRN). Arterial blood pressure and compression rate were determined from manually extracted arterial line waveform data during the first 10 min of CPR. The primary outcome was survival to hospital discharge. Modified Poisson regression models assessed the association between rate categories (80-<100, 100-120 [Guidelines], >120-140, >140) and outcomes., Results: Compression rate data were available for 164 patients. More than half (98/164; 60%) were <1 year old. Return of circulation was achieved in 148/164 (90%); survival to hospital discharge in 77/164 (47%). Percentage of events with average rate within Guidelines was 32.9%. Compared to Guidelines, higher rate categories were associated with lower systolic blood pressures (>120-140, p = 0.010; >140, p = 0.077), but not survival. A rate between 80-<100 per minute was associated with a higher rate of survival to hospital discharge (aRR 1.92, CI95 1.13, 3.29, p = 0.017) and survival with favorable neurological outcome (aRR 2.12, CI95 1.09, 4.13, p = 0.027) compared to Guidelines., Conclusion: Non-compliance with compression rate Guidelines was common in this multicenter cohort. Among ICU patients, slightly lower rates were associated with improved outcomes compared to Guidelines., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The "Age of Blood in Children in Pediatric Intensive Care Unit" (ABC PICU) study is a randomized controlled trial (RCT) that aims to determine if red blood cell (RBC) unit storage age affects outcomes in critically ill children. While RBCs can be stored for up to 42 days in additive solutions, their efficacy and safety after long-term storage have been challenged. Preclinical and clinical observational evidence suggests loss of efficacy and lack of safety of older RBC units, especially in more vulnerable populations such as critically ill children. Because there is a belief that shorter storage will improve outcomes, some physicians and institutions systematically transfuse fresh RBCs to children. Conversely, the standard practice of blood banks is to deliver the oldest available RBC unit (first-in, first-out policy) in order to decrease wastage., Methods/design: The ABC PICU study, is a double-blind superiority trial comparing the development of "New or Progressive Multiple Organ Dysfunction Syndrome" (NPMODS) in 1538 critically ill children randomized to either transfusion with RBCs stored for ≤ 7 days or to standard-issue RBCs (oldest in inventory). Patients are being recruited from 52 centers in the US, Canada, France, Italy, and Israel., Discussion: The ABC PICU study should have significant implications for blood procurement services. A relative risk reduction of 33% is postulated in the short-storage arm. If a difference is found, this will indicate that fresher RBCs do improve outcomes in the pediatric intensive care unit population and would justify that use in critically ill children. If no difference is found, this will reassure clinicians and transfusion medicine specialists regarding the safety of the current system of allocating the oldest RBC unit in inventory and will discourage clinicians from preferentially requesting fresher blood for critically ill children., Trial Registration: ClinicalTrials.gov, ID: NCT01977547 . Registered on 6 November 2013.

Objectives: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model., Methods: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis., Results: DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming., Conclusions: DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.