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OBJECTIVE: To describe our experience with pediatric donation after cardiac death. DESIGN: Retrospective chart review of all cases of donation after cardiac death from 1995 to 2005. SETTING: The Children's Hospital of Philadelphia pediatric intensive care unit. PATIENTS: Twelve patients who were pediatric organ donors after cardiac death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Charts for 12 patients were located, and donation after cardiac death was confirmed. There were two females and ten males. Patient age ranged from 1 to 17 yrs (mean 8 yrs). Four patients had severe traumatic brain injury, and eight patients had hypoxic ischemic encephalopathy. The organs procured were 24 kidneys, eight livers, four lungs, and one pancreas. The organs transplanted were 23 kidneys, four livers, and one pancreas. Ten of 12 cases of withdrawal of life-sustaining support occurred in the operating room area; the other two occurred in the holding area and the postanesthesia care unit. Children received a wide range of medications at the time of extubation. No neuromuscular blockers were used. The time of extubation to time of death ranged from 4 mins to 30 mins, with a mean of 14.5 mins. Death was declared based on cardiac asystole confirmed by auscultation and transthoracic impedance, with organ procurement initiated 5 mins later. Regarding who initiated conversation about donation after cardiac death, nine cases were family initiated, one case was physician initiated, and in two there was a collaborative approach with the physician and representative from the organ procurement organization. Of the organs transplanted, all organs other than one kidney and one split liver graft were functioning at 1 yr post-transplant. CONCLUSIONS: Pediatric donation after cardiac death can be performed successfully; its impact on end-of-life care and bereavement needs further investigation. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

To date, health disparities in critically ill children have largely been studied within, not across, specific intensive care unit (ICU) settings, thus impeding collaboration which may help advance the care of critically ill children. The aim of this scoping review is to summarize the literature intentionally designed to examine health disparities, across 3 primary ICU settings (neonatal ICU, pediatric ICU, and cardiac ICU) in the United States. We included over 50 studies which describe health disparities across race and/or ethnicity, area-level indices, insurance status, socioeconomic position, language, and distance., Competing Interests: Disclosure The work of C-A. Gathers and D.C. Murosko was supported by the NIH, United States-funded training grant T32HL098054., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Resuscitation with chest compressions and positive pressure ventilation in Bidirectional Glenn (BDG) or Fontan physiology may compromise passive venous return and accentuate neurologic injury. We hypothesized that arterial pressure and survival would be better in BDG than Fontan patients., Methods: Secondary analyses of the Pediatric Intensive Care Quality of CPR and Improving Outcomes from Pediatric Cardiac Arrest databases. P-values were considered significant if < 0.05., Results: In total, 64 patients had either BDG (42/64, 66%) or Fontan (22/64, 34%) anatomy. Return of spontaneous circulation was achieved in 76% of BDG patients versus 59% of Fontan patients and survival with favorable neurologic outcome in 22/42 (52%) BDG versus 6/22 (27%) Fontan patients, p = 0.067. Twelve of 24 (50%) BDG and 2/7 (29%) Fontan patients who survived to discharge suffered new morbidity as defined by worsening Functional Status Score. More BDG patients achieved adequate DBP (≥25 mmHg for neonates and infants; ≥ 30 mmHg for children) than Fontan patients (21/23 (91%) vs. 5/11 (46%), p = 0.007)., Conclusions: Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after CPR, likely driven by inadequate diastolic blood pressure during resuscitation. One half of the BDG patients who survived to hospital discharge had new neurologic morbidity., Background: Cardiac arrest in patients with congenital heart disease (CHD) may present challenges to resuscitation based on the unique cardiovascular physiology resulting from surgical palliation. Recent resuscitation guidelines for CHD patients highlight the lack of data surrounding these special patient populations. 1 Univentricular heart disease is palliated by a series of cardiac surgeries that stepwise result in passive pulmonary perfusion from the systemic venous system directly to the pulmonary vascular bed. The bidirectional Glenn (BDG) palliation directly anastomoses the superior vena cava (SVC) to the pulmonary arterial system and leaves normal inferior vena cava (IVC) venous return to the heart. 2 The Fontan palliation baffles IVC flow directly to the pulmonary vascular bed which relieves cyanosis due to right to left shunting, but requires systemic ventricular preload to be directly dependent upon pulmonary vascular resistance and intrathoracic pressures. 3 IMPACT STATEMENT: Hemodynamic waveforms from 2 large prospective observational studies now allow for exploration of physiology during cardiopulmonary resuscitation for unique anatomy associated with single ventricle congenital heart disease. Fewer patients with Fontan physiology (46%) achieved an adequate diastolic blood pressure (defined as ≥ 25 mmHg for neonates and infants and ≥ 30 mmHg for children) than bidirectional Glenn patients during cardiopulmonary resuscitation (91%, p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after cardiopulmonary resuscitation. Of the bidirectional Glenn patients who survived, 50% developed a new morbidity as quantified by the Functional Status Score., (© 2024. The Author(s).)

Background: Opioids are commonly used to provide analgesia during and after congenital heart surgery. The effects of exposure to opioids on neurodevelopment in neonates and infants are not well understood., Objectives: This study sought to evaluate the associations between cumulative opioid exposure (measured in morphine mg equivalent) over the first year of life and 2-year neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-Third/Fourth Edition [Bayley-III/IV] cognitive, language, and motor scores)., Methods: A single-center retrospective cohort study of infants undergoing congenital heart surgery was performed. Adjustment for measurable confounders was performed through multivariable linear regression., Results: A total of 526 subjects were studied, of whom 32% underwent Society for Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 or 5 operations. In unadjusted analyses, higher total exposure to opioids was associated with worse scores across all 3 Bayley-III/IV domain scores (all P < 0.05). After adjustment for measured confounders, greater opioid exposure was associated with lower Bayley-III/IV scores (cognitive: β = -1.0 per log-transformed morphine mg equivalents, P = 0.04; language: β = -1.2, P = 0.04; and motor: β = -1.1, P = 0.02). Total hospital length of stay, prematurity, genetic syndromes, and worse neighborhood socioeconomic status (represented either by Social Vulnerability Index or Childhood Opportunity Index) were all associated with worse Bayley-III/IV scores across all domains (all P < 0.05)., Conclusions: Greater postnatal exposure to opioids was associated with worse neurodevelopmental outcomes across cognitive, language, and motor domains, independent of other less modifiable factors. This finding should motivate research and efforts to explore reduction in opioid exposure while preserving quality cardiac intensive care., Competing Interests: Funding Support and Author Disclosures This research utilized resources from The Children's Hospital of Philadelphia Cardiac Center Clinical Research Core. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes., Design: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing., Setting: Eighteen PICUs and pediatric cardiac ICUs in the United States., Patients: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded., Interventions: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes., Measurements and Main Results: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01)., Conclusions: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration., Competing Interests: Drs. Kienzle, Berg, Morgan, Reeder, Carcillo, Carpenter, Hall, Horvat, Franzon, Frazier, Friess, Maa, Manga, McQuillen, Meert, Mourani, Naim, Pollack, Sapru, Schnieter, Wolfe, and Sutton received National Institutes of Health (NIH) grant funding to their institution related to this project. Dr. Kienzle disclosed the study was supported by the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; U01HD049934, UG1HD049981, UG1HD049983, UG1HD050096, UG1HD063108, UG1HD083166, UG1HD083170, and UG1HD083171) and National Heart, Lung, and Blood Institute (NHLBI; R01HL131544 and K23HL148541) and by the Children’s Hospital of Philadelphia Research Institute Resuscitation Science Center. Dr. Berg reports membership on Data Safety Monitoring Boards. Dr. Carcillo received funding from the NICHD and the National Institute of General Medical Sciences. Dr. Diddle received funding from Mallinckrodt Pharmaceuticals. Dr. Friess received funding for expert testimony. Drs. Berg’s and Maa’s institutions received funding from the NHLBI. Drs. Berg, Carpenter, Horvat, and McQuillen institutions received funding from the NICHD. Drs. Morgan and Sutton report volunteer leadership roles with the American Heart Association. Dr. Morgan’s institution received funding from the NHLBI (K23HL148541). Dr. Hall received funding from the American Board of Pediatrics, AbbVie, Kiadis, Partner Therapeutics, and Sobi. Dr. Nadkarni receives unrestricted research grants to his institution from the NIH, Agency for Healthcare Research and Quality, Department of Defense, Zoll Medical, Nihon Kohden, Resuscitation Quality Improvement Partners, American Heart Association, and Laerdal Foundation. He serves as the president of the Society of Critical Care Medicine (SCCM). The views expressed are his, and not intended to represent the views of the SCCM. Dr. Wolfe received funding for speaking fees. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: To identify delivery room (DR) characteristics of patients with transposition of the great arteries (TGA) who underwent preoperative balloon atrial septostomy (BAS)., Study Design: Retrospective cohort study of all patients with prenatally diagnosed TGA delivered at our center between 2013 and 2023 who underwent arterial switch operation during the newborn admission., Results: A total of 168 patients were included (median gestational age 39.5 weeks, 64% male, 33% with ventricular septal defect, 8% with aortic arch hypoplasia). BAS was performed in 84 patients (50%). Patients who underwent BAS had higher proportion of intubation in the DR (87% vs 33%, P < .001), lower maximum oxygen saturation in the first 10 minutes (64% vs 74%, P < .001) and 20 minutes (71% vs 81%, P < .001) of life, and lower maximum oxygen saturation at any point in the DR (79% vs 87%, P < .001). Adjusting for confounders (ventricular septal defect, aortic arch anomaly, 5-minute Apgar, birth weight), intubation in the DR (aOR 9.5, 95% CI 3.9, 25.0) and lower maximum oxygen saturation in the DR (aOR 0.9, 95% CI 0.8, 0.9) were independently associated with BAS. By receiver operating characteristic analysis, a maximum oxygen saturation of less than 86% at any time point in the DR discriminated for BAS with a specificity of 0.88, sensitivity of 0.70, and area under the curve of 0.82., Conclusions: Intubation and lower oxygen saturation in the DR are independently associated with BAS in patients with TGA born at our center. A maximum DR saturation of less than 86% best discriminates patients who undergo BAS in our population., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

Background: Tracheal intubation (TI)-associated cardiac arrest (TI-CA) occurs in 1.7% of pediatric ICU TIs. Our objective was to evaluate resuscitation characteristics and outcomes between cardiac arrest patients with and without TI-CA., Methods: Secondary analysis of cardiac arrest patients in both ICU-RESUS trial and ancillary CPR-NOVA study. The primary exposure was TI-CA, defined as cardiac arrest occurred during TI procedure or within 20 min after endotracheal tube placement. The primary outcome was survival to hospital discharge with favorable neurological outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged)., Results: Among 315 children with cardiac arrests, 48 (15.2%) met criteria for TI-CA. Pre-existing medical conditions were similar between groups. Pre-arrest non-invasive mechanical ventilation was more common among TI-CA patients (18/48, 37.5%) compared to non-TI-CA patients (35/267, 13.1%). In 48% (23/48), the TI-CA occurred within 20 min after intubation (i.e., not during intubation). Duration of CPR was longer in TI-CA patients (median 11.0 min, interquartile range [IQR]: 2.5, 35.5) than non-TI-CA patients (median 5.0 min, IQR 2.0, 21.0), p = 0.03. Return of spontaneous circulation occurred in 32/48 (66.7%) TI-CA versus 186/267 (69.7%) non-TI-CA, p = 0.73. Survival to hospital discharge with favorable neurological outcome occurred in 29/48 (60.4%) TI-CA versus 146/267 (54.7%) non-TI-CA, p = 0.53., Conclusions: Fifteen percent of these pediatric ICU cardiac arrests were associated with TI. Half of TI-CA occurred after endotracheal tube placement. While duration of CPR was longer in TI-CA patients, there were no differences in unadjusted outcomes following TI-CA versus non-TI-CA., Trial Registration: The ICU-RESUS (ClinicalTrials.gov Identifier: NCT02837497)., (© 2024. The Author(s).)

Background and Objectives: There are limited tools available following cardiac arrest to prognosticate neurologic outcomes. Prior retrospective and single center studies have demonstrated early EEG features are associated with neurologic outcome. This study aimed to evaluate the prognostic value of EEG for pediatric in-hospital cardiac arrest (IHCA) in a prospective, multicenter study., Methods: This cohort study is a secondary analysis of the ICU-Resuscitation trial, a multicenter randomized interventional trial conducted at 18 pediatric and pediatric cardiac ICUs in the United States. Patients who achieved return of circulation (ROC) and had post-ROC EEG monitoring were eligible for inclusion. Patients < 90 days old and those with pre-arrest Pediatric Cerebral Performance Category (PCPC) scores > 3 were excluded. EEG features of interest included EEG Background Category, and presence of focal abnormalities, sleep spindles, variability, reactivity, periodic and rhythmic patterns, and seizures. The primary outcome was survival to hospital discharge with favorable neurologic outcome. Associations between EEG features and outcomes were assessed with multivariable logistic regression. Prediction models with and without EEG Background Category were developed and receiver operator characteristic curves compared., Results: Of the 1129 patients with an index cardiac arrest who achieved ROC in the parent study, 261 had EEG within 24 h of ROC, of which 151 were evaluable. The cohort included 57% males with a median age of 1.1 years (IQR 0.4, 6.8). EEG features including EEG Background Category, sleep spindles, variability, and reactivity were associated with survival with favorable outcome and survival, (all p < 0.001). The addition of EEG Background Category to clinical models including age category, illness category, PRISM score, duration of CPR, first documented rhythm, highest early post-arrest arterial lactate improved the prediction accuracy achieving an AUROC of 0.84 (CI 0.77-0.92), compared to AUROC of 0.76 (CI 0.67-0.85) (p = 0.005) without EEG Background Category., Conclusion: This multicenter study demonstrates the value of EEG, in the first 24 h following ROC, for predicting survival with favorable outcome after a pediatric IHCA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness., Methods: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status., Results: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p < 0.001)., Conclusions: In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset., (© 2024. The Author(s).)

Importance: Cardiopulmonary resuscitation (CPR) duration is associated with cardiac arrest survival., Objectives: To describe characteristics associated with CPR duration among hospitalized children without return of circulation (ROC) (patient-level analysis) and determine whether hospital median CPR duration in patients without ROC is associated with survival (hospital-level analysis)., Design, Setting, and Participants: This retrospective cohort study of patients undergoing pediatric in-hospital CPR between January 1, 2000, and December 31, 2021, used data from the Get With the Guidelines-Resuscitation registry. Children receiving chest compressions for at least 2 minutes and/or defibrillation were included in the patient-level analysis. For the hospital-level analysis, sites with at least 20 total events and at least 5 events without ROC were included. Data were analyzed from December 1, 2022, to November 15, 2023., Exposures: For the patient-level analysis, the exposure was CPR duration in patients without ROC. For the hospital-level analysis, the exposure was quartile of median CPR duration in events without ROC at each hospital., Main Outcomes and Measures: For the patient-level analysis, outcomes were patient and event factors, including race and ethnicity and event location; we used a multivariable hierarchical linear regression model to assess factors associated with CPR duration in patients without ROC. For the hospital-level analysis, the main outcome was survival to discharge among all site events; we used a random intercept multivariable hierarchical logistic regression model to examine the association between hospital quartile of CPR duration and survival to discharge., Results: Of 13 899 events, 3859 patients did not have ROC (median age, 7 months [IQR, 0 months to 7 years]; 2175 boys [56%]). Among event nonsurvivors, median CPR duration was longer in those with initial rhythms of bradycardia with poor perfusion (8.37 [95% CI, 5.70-11.03] minutes; P < .001), pulseless electrical activity (8.22 [95% CI, 5.44-11.00] minutes; P < .001), and pulseless ventricular tachycardia (6.17 [95% CI, 0.09-12.26] minutes; P = .047) (vs asystole). Shorter median CPR duration was associated with neonates compared with older children (-4.86 [95% CI, -8.88 to -0.84] minutes; P = .02), emergency department compared with pediatric intensive car7 e unit location (-4.02 [95% CI, -7.48 to -0.57] minutes; P = .02), and members of racial or ethnic minority groups compared with White patients (-3.67 [95% CI, -6.18 to -1.17]; P = .004). Among all CPR events, the adjusted odds of survival to discharge differed based on hospital quartile of median CPR duration among events without ROC; compared with quartile 1 (15.0-25.9 minutes), the adjusted odds ratio for quartile 2 (26.0-29.4 minutes) was 1.22 (95% CI, 1.09-1.36; P < .001); for quartile 3 (29.5-32.9 minutes), 1.23 (95% CI, 1.08-1.39; P = .002); and for quartile 4 (33.0-53.0 minutes), 1.04 (95% CI, 0.91-1.19; P = .58)., Conclusions and Relevance: In this retrospective cohort study of pediatric in-hospital CPR, several factors, including age and event location, were associated with CPR duration in event nonsurvivors. The odds of survival to discharge were lower for patients at hospitals with the shortest and longest median CPR durations among events without ROC. Further studies are needed to determine the optimal duration of CPR during pediatric in-hospital cardiac arrest and to provide training guidelines for resuscitation teams to eliminate disparities in resuscitation care.

Rationale: Adult and pediatric studies provide conflicting data regarding whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia, and/or hypocapnia are associated with worse outcomes. Objectives: We sought to determine whether postarrest hypoxemia or postarrest hyperoxemia is associated with lower rates of survival to hospital discharge, compared with postarrest normoxemia, and whether postarrest hypocapnia or hypercapnia is associated with lower rates of survival, compared with postarrest normocapnia. Methods: An embedded prospective observational study during a multicenter interventional cardiopulmonary resuscitation trial was conducted from 2016 to 2021. Patients ⩽18 years old and with a corrected gestational age of ≥37 weeks who received chest compressions for cardiac arrest in one of the 18 intensive care units were included. Exposures during the first 24 hours postarrest were hypoxemia, hyperoxemia, or normoxemia-defined as lowest arterial oxygen tension/pressure (Pa O 2 ) <60 mm Hg, highest Pa O 2 ⩾200 mm Hg, or every Pa O 2 60-199 mm Hg, respectively-and hypocapnia, hypercapnia, or normocapnia, defined as lowest arterial carbon dioxide tension/pressure (Pa CO 2 ) <30 mm Hg, highest Pa CO 2 ⩾50 mm Hg, or every Pa CO 2 30-49 mm Hg, respectively. Associations of oxygenation and carbon dioxide group with survival to hospital discharge were assessed using Poisson regression with robust error estimates. Results: The hypoxemia group was less likely to survive to hospital discharge, compared with the normoxemia group (adjusted relative risk [aRR] = 0.71; 95% confidence interval [CI] =  0.58-0.87), whereas survival in the hyperoxemia group did not differ from that in the normoxemia group (aRR = 1.0; 95% CI = 0.87-1.15). The hypercapnia group was less likely to survive to hospital discharge, compared with the normocapnia group (aRR = 0.74; 95% CI = 0.64-0.84), whereas survival in the hypocapnia group did not differ from that in the normocapnia group (aRR = 0.91; 95% CI = 0.74-1.12). Conclusions: Postarrest hypoxemia and hypercapnia were each associated with lower rates of survival to hospital discharge.

Introduction: Disparities in CHD outcomes exist across the lifespan. However, less is known about disparities for patients with CHD admitted to neonatal ICU. We sought to identify sociodemographic disparities in neonatal ICU admissions among neonates born with cyanotic CHD., Materials & Methods: Annual natality files from the US National Center for Health Statistics for years 2009-2018 were obtained. For each neonate, we identified sex, birthweight, pre-term birth, presence of cyanotic CHD, and neonatal ICU admission at time of birth, as well as maternal age, race, ethnicity, comorbidities/risk factors, trimester at start of prenatal care, educational attainment, and two measures of socio-economic status (Special Supplemental Nutrition Program for Women, Infants, and Children [WIC] status and insurance type). Multivariable logistic regression models were fit to determine the association of maternal socio-economic status with neonatal ICU admission. A covariate for race/ethnicity was then added to each model to determine if race/ethnicity attenuate the relationship between socio-economic status and neonatal ICU admission., Results: Of 22,373 neonates born with cyanotic CHD, 77.2% had a neonatal ICU admission. Receipt of WIC benefits was associated with higher odds of neonatal ICU admission (adjusted odds ratio [aOR] 1.20, 95% CI 1.1-1.29, p < 0.01). Neonates born to non-Hispanic Black mothers had increased odds of neonatal ICU admission (aOR 1.20, 95% CI 1.07-1.35, p < 0.01), whereas neonates born to Hispanic mothers were at lower odds of neonatal ICU admission (aOR 0.84, 95% CI 0.76-0.93, p < 0.01)., Conclusion: Maternal Black race and low socio-economic status are associated with increased risk of neonatal ICU admission for neonates born with cyanotic CHD. Further work is needed to identify the underlying causes of these disparities.

Objectives: Cannulation for extracorporeal membrane oxygenation during active extracorporeal cardiopulmonary resuscitation (ECPR) is a method to rescue patients refractory to standard resuscitation. We hypothesized that early arrest hemodynamics and end-tidal C o2 (ET co2 ) are associated with survival to hospital discharge with favorable neurologic outcome in pediatric ECPR patients., Design: Preplanned, secondary analysis of pediatric Utstein, hemodynamic, and ventilatory data in ECPR patients collected during the 2016-2021 Improving Outcomes from Pediatric Cardiac Arrest study; the ICU-RESUScitation Project (ICU-RESUS; NCT02837497)., Setting: Eighteen ICUs participated in ICU-RESUS., Patients: There were 97 ECPR patients with hemodynamic waveforms during cardiopulmonary resuscitation., Interventions: None., Measurements and Main Results: Overall, 71 of 97 patients (73%) were younger than 1 year old, 82 of 97 (85%) had congenital heart disease, and 62 of 97 (64%) were postoperative cardiac surgical patients. Forty of 97 patients (41%) survived with favorable neurologic outcome. We failed to find differences in diastolic or systolic blood pressure, proportion achieving age-based target diastolic or systolic blood pressure, or chest compression rate during the initial 10 minutes of CPR between patients who survived with favorable neurologic outcome and those who did not. Thirty-five patients had ET co2 data; of 17 survivors with favorable neurologic outcome, four of 17 (24%) had an average ET co2 less than 10 mm Hg and two (12%) had a maximum ET co2 less than 10 mm Hg during the initial 10 minutes of resuscitation., Conclusions: We did not identify an association between early hemodynamics achieved by high-quality CPR and survival to hospital discharge with favorable neurologic outcome after pediatric ECPR. Candidates for ECPR with ET co2 less than 10 mm Hg may survive with favorable neurologic outcome., Competing Interests: Drs. Yates’s, Naim’s, Reeder’s, Berg’s, Carpenter’s, Dean’s, Fink’s, Frazier’s, Hall’s, Manga’s, Mourani’s, Sapru’s, Wessel’s, Wolfe’s, Zuppa’s, and Meert’s institution received funding from the National Institutes of Health (NIH). Drs. Yates, Naim, Reeder, Banks, Berg, Carcillo, Carpenter, Dean, Fink, Franzon, Frazier, Freiss, Hall, Horvat, McQuillen, Mourani, Pollack, Sapru, Schneiter, Wessel, Zuppa, Sutton, and Meert received support for article research from the NIH. Drs. Banks’s, Carcillo’s, Horvat’s, Maa’s, McQuillen’s, Pollack’s, and Schneiter’s institutions received funding from the National Institute for Child Health and Human Development. Dr. Banks disclosed government work. Drs. Carcillo’s, Maa’s, and Sutton’s institutions received funding from the National Heart, Lung, and Blood Institute (NHLBI). Dr. Carcillo’s institution received funding from the National Institute for General Medical Sciences. Dr. Diddle disclosed that he is a consultant with Mallinckrodt Pharmaceuticals. Dr. Franzon received funding from Health Navigator Foundation; she disclosed that she is a site investigator for a multisite NIH funded project. Dr. Frazier’s institution received funding from the Neurocritical Care Society and the American Board of Pediatrics. Dr. Hall received funding from AbbVie, Kiadis, and the American Board of Pediatrics. Dr. Morgan’s institution received funding from the NHLBI (K23HL148541). Dr. Wolfe received funding from The Debriefing Academy. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Although neonates and children with congenital heart disease are primarily hospitalized for cardiac and pulmonary diseases, they are also at an increased risk for neurologic injury due to both empiric differences that can exist in their nervous systems and acquired injury from cardiopulmonary pathology and interventions. Although early efforts in care focused on survival after reparative cardiac surgery, as surgical and anesthetic techniques have evolved and survival rates accordingly improved, the focus has now shifted to maximizing outcomes among survivors. Children and neonates with congenital heart disease experience seizures and poor neurodevelopmental outcomes at a higher rate than age-matched counterparts. The aim of neuromonitoring is to help clinicians identify patients at highest risk for these outcomes to implement strategies to mitigate these risks and to also help with neuroprognostication after an injury has occurred. The mainstays of neuromonitoring are (1) electroencephalographic monitoring to evaluate brain activity for abnormal patterns or changes and to identify seizures, (2) neuroimaging to reveal structural changes and evidence of physical injury in and around the brain, and (3) near-infrared spectroscopy to monitor brain tissue oxygenation and detect changes in perfusion. This review will detail the aforementioned techniques and their use in the care of pediatric patients with congenital heart disease., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Aim: Pediatric cardiopulmonary resuscitation (CPR) guidelines recommend starting CPR for heart rates (HRs) less than 60 beats per minute (bpm) with poor perfusion. Objectives were to (1) compare HRs and arterial blood pressures (BPs) prior to CPR among patients with clinician-reported bradycardia with poor perfusion ("BRADY") vs. pulseless electrical activity (PEA); and (2) determine if hemodynamics prior to CPR are associated with outcomes., Methods and Results: Prospective observational cohort study performed as a secondary analysis of the ICU-RESUScitation trial (NCT028374497). Comparisons occurred (1) during the 15 seconds "immediately" prior to CPR and (2) over the two minutes prior to CPR, stratified by age (≤1 year, >1 year). Poisson regression models assessed associations between hemodynamics and outcomes. Primary outcome was return of spontaneous circulation (ROSC). Pre-CPR HRs were lower in BRADY vs. PEA (≤1 year: 63.8 [46.5, 87.0] min -1 vs. 120 [93.2, 150.0], p < 0.001; >1 year: 67.4 [54.5, 87.0] min -1 vs. 100 [66.7, 120], p < 0.014). Pre-CPR pulse pressure was higher among BRADY vs. PEA (≤1 year (12.9 [9.0, 28.5] mmHg vs. 10.4 [6.1, 13.4] mmHg, p > 0.001). Pre-CPR pulse pressure ≥ 20 mmHg was associated with higher rates of ROSC among PEA (aRR 1.58 [CI95 1.07, 2.35], p = 0.022) and survival to hospital discharge with favorable neurologic outcome in both groups (BRADY: aRR 1.28 [CI95 1.01, 1.62], p = 0.040; PEA: aRR 1.94 [CI95 1.19, 3.16], p = 0.008). Pre-CPR HR ≥ 60 bpm was not associated with outcomes., Conclusions: Pulse pressure and HR are used clinically to differentiate BRADY from PEA. A pre-CPR pulse pressure >20 mmHg was associated with improved patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To assess associations between outcome and cardiopulmonary resuscitation (CPR) quality for in-hospital cardiac arrest (IHCA) in children with medical cardiac, surgical cardiac, or noncardiac disease., Design: Secondary analysis of a multicenter cluster randomized trial, the ICU-RESUScitation Project (NCT02837497, 2016-2021)., Setting: Eighteen PICUs., Patients: Children less than or equal to 18 years old and greater than or equal to 37 weeks postconceptual age receiving chest compressions (CC) of any duration during the study., Interventions: None., Measurements and Main Results: Of 1,100 children with IHCA, there were 273 medical cardiac (25%), 383 surgical cardiac (35%), and 444 noncardiac (40%) cases. Favorable neurologic outcome was defined as no more than moderate disability or no worsening from baseline Pediatric Cerebral Performance Category at discharge. The medical cardiac group had lower odds of survival with favorable neurologic outcomes compared with the noncardiac group (48% vs 55%; adjusted odds ratio [aOR] [95% CI], aOR 0.59 [95% CI, 0.39-0.87], p = 0.008) and surgical cardiac group (48% vs 58%; aOR 0.64 [95% CI, 0.45-0.9], p = 0.01). We failed to identify a difference in favorable outcomes between surgical cardiac and noncardiac groups. We also failed to identify differences in CC rate, CC fraction, ventilation rate, intra-arrest average target diastolic or systolic blood pressure between medical cardiac versus noncardiac, and surgical cardiac versus noncardiac groups. The surgical cardiac group had lower odds of achieving target CC depth compared to the noncardiac group (OR 0.15 [95% CI, 0.02-0.52], p = 0.001). We failed to identify a difference in the percentage of patients achieving target CC depth when comparing medical cardiac versus noncardiac groups., Conclusions: In pediatric IHCA, medical cardiac patients had lower odds of survival with favorable neurologic outcomes compared with noncardiac and surgical cardiac patients. We failed to find differences in CPR quality between medical cardiac and noncardiac patients, but there were lower odds of achieving target CC depth in surgical cardiac compared to noncardiac patients., Competing Interests: This study was funded by the following grants from the National Institute of Health National Heart, Lung and Blood Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development: R01HL131544, R01HD049934, UG1HD049981, UG1HD049983, UG1050096, UG1HD063108, UG1HD083166, UG1HD083170, UG1HD083171, and K23HL148541. Drs. Sutton and Manga’s institution received funding from the National Heart, Lung, and Blood Institute. Drs. Sutton, Reeder, Bell, Berg, Carcillo, Carpenter, Dean, Fernandez, Fink, Frazier, Friess, Graham, Hall, Horvat, Manga, McQuillen, Meert, Morgan, Mourani, Nadkarni, Pollack, Sapru, Schneiter, Wessel, Yates, Zuppa, and Naim received support for article research from the National Institutes of Health (NIH). Drs. Reeder, Bell, Berg, Carcillo, Carpenter, Dean, Fink, Friess, Hall, Meert, Morgan, Mourani, Nadkarni, Pollack, Sapru, Wessel, Yates, Zuppa, and Naim’s institutions received funding from the NIH. Dr. Carcillo’s institution received funding from the National Institute of General Medical Sciences. Dr. Diddle received funding from Mallinckrodt Pharmaceuticals via his institution. Dr. Fink’s institution received funding from the Neurocritical Care Society; she received funding from the American Board of Pediatrics. Dr. Franzon’s institution received funding from ICU-RESUScitation/Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Dr. Hall received funding from Abbvie and Kiadis. Drs. Horvat, Maa, Manga, McQuillen, and Schneiter’s institutions received funding from the National Institute of Child Health and Human Development. Dr. Nadkarni’s institution received funding from Laerdal Foundation-RQI Programs, Nihon-Kohden, Philips, Defibtech, and HeartHero; he received funding from the Society of Critical Care Medicine as President (2023–2024) and the NIH; he disclosed that he is a volunteer for Citizen cardiopulmonary resuscitation Foundation Board, the American Heart Association Committees, and the International Liaison Committee on Resuscitation Board. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Historically, our center has primarily used deep hypothermic circulatory arrest, but in recent years some surgeons have selectively used regional cerebral perfusion as an alternative. We aimed to compare the incidence of postoperative electroencephalographic seizure incidence in neonates undergoing surgery with regional cerebral perfusion and deep hypothermic circulatory arrest., Methods: A retrospective analysis was performed in neonates who underwent surgery between 2012 and 2022 with either deep hypothermic circulatory arrest or regional cerebral perfusion with routine postoperative continuous electroencephalography monitoring for 48 hours. Propensity matching was performed to compare postoperative seizure risk between the 2 groups., Results: Among 1136 neonates undergoing cardiac surgery with cardiopulmonary bypass, regional cerebral perfusion was performed in 99 (8.7%) and deep hypothermic circulatory arrest in 604 (53%). The median duration of regional cerebral perfusion was 49 minutes (interquartile range, 38-68) and deep hypothermic circulatory arrest was 41 minutes (interquartile range, 31-49). The regional cerebral perfusion group had significantly longer total support, cardiopulmonary bypass, and aortic crossclamp times. Overall seizure incidence was 11% (N = 76) and 13% (N = 35) in the most recent era (2019-2022). The unadjusted seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 64, 11%). After propensity matching, the seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 37, 12%) (odds ratio, 0.97; 95% CI, 0.55-1.71; P = . 92)., Conclusions: In this contemporary single-center experience, the incorporation of regional cerebral perfusion did not result in a change in seizure incidence in comparison with deep hypothermic circulatory arrest. However, unmeasured confounders may have impacted these findings. Further studies are needed to determine the impact, if any, of regional cerebral perfusion on postoperative seizure incidence., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Introduction: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge., Methods: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled in the ICU-RESUScitation trial (NCT02837497). The lowest documented systolic BP (SBP) and diastolic BP (DBP) were percentile-adjusted for age, height and sex. Receiver operator characteristic curves and cubic spline analyses controlling for illness category and presence of pre-arrest hypotension were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Optimal cutoffs for post-arrest BP thresholds were based on analysis of receiver operator characteristic curves and spline curves. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes., Results: Among 693 index events with 0-6 h post-arrest BP data, identified thresholds were: SBP > 10th percentile and DBP > 50th percentile for age, sex and height. Fifty-one percent (n = 352) of subjects had lowest SBP above threshold and 50% (n = 346) had lowest DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP: aRR 1.21 [95% CI 1.10, 1.33]; DBP: aRR 1.23 [1.12, 1.34]) and survival to hospital discharge with favorable neurologic outcome (SBP: aRR 1.22 [1.10, 1.35]; DBP: aRR 1.27 [1.15, 1.40]) (all p < 0.001)., Conclusions: Following pediatric IHCA, subjects had higher rates of survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome when BP targets above a threshold of SBP > 10th percentile for age and DBP > 50th percentile for age during the first 6 h post-arrest., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aim: To evaluate associations between characteristics of simulated point-of-care cardiopulmonary resuscitation (CPR) training with simulated and actual intensive care unit (ICU) CPR performance, and with outcomes of children after in-hospital cardiac arrest., Methods: This is a pre-specified secondary analysis of the ICU-RESUScitation Project; a prospective, multicentre cluster randomized interventional trial conducted in 18 ICUs from October 2016-March 2021. Point-of-care bedside simulations with real-time feedback to allow multidisciplinary ICU staff to practice CPR on a portable manikin were performed and quality metrics (rate, depth, release velocity, chest compression fraction) were recorded. Actual CPR performance was recorded for children 37 weeks post-conceptual age to 18 years who received chest compressions of any duration, and included intra-arrest haemodynamics and CPR mechanics. Outcomes included survival to hospital discharge with favourable neurologic status., Results: Overall, 18,912 point-of-care simulations were included. Simulation characteristics associated with both simulation and actual performance included site, participant discipline, and timing of simulation training. Simulation characteristics were not associated with survival with favourable neurologic outcome. However, participants in the top 3 sites for improvement in survival with favourable neurologic outcome were more likely to have participated in a simulation in the past month, on a weekday day, to be nurses, and to achieve targeted depth of compression and chest compression fraction goals during simulations than the bottom 3 sites., Conclusions: Point-of-care simulation characteristics were associated with both simulated and actual CPR performance. More recent simulation, increased nursing participation, and simulation training during daytime hours may improve CPR performance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘This study was funded by the following grants from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute and the Eunice Kennedy ShriverNational Institute of Child Health and Human Development: R01HL131544, U01HD049934, UG1HD049981, UG1HD049983, UG1HD050096, UG1HD063108, UG1HD083166, UG1HD083170, UG1HD083171, and K23HL148541. Two of the co-authors, Dr. Robert Berg and Dr. Vinay Nadkarni, are members of the Resuscitation Editorial Board.’., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Previous studies have identified pulmonary hypertension (PH) as a relatively common diagnosis in children with in-hospital cardiac arrest (IHCA), and preclinical laboratory studies have found poor outcomes and low systemic blood pressures during CPR for PH-associated cardiac arrest. The objective of this study was to determine the prevalence of PH among children with IHCA and the association between PH diagnosis and intra-arrest physiology and survival outcomes., Methods: This was a prospectively designed secondary analysis of patients enrolled in the ICU-RESUS clinical trial (NCT02837497). The primary exposure was a pre-arrest diagnosis of PH. The primary survival outcome was survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline). The primary physiologic outcome was event-level average diastolic blood pressure (DBP) during CPR., Results: Of 1276 patients with IHCAs during the study period, 1129 index IHCAs were enrolled; 184 (16.3%) had PH and 101/184 (54.9%) were receiving inhaled nitric oxide at the time of IHCA. Survival with favorable neurologic outcome was similar between patients with and without PH on univariate (48.9% vs. 54.4%; p = 0.17) and multivariate analyses (aOR 0.82 [95%CI: 0.56, 1.20]; p = 0.32). There were no significant differences in CPR event outcome or survival to hospital discharge. Average DBP, systolic BP, and end-tidal carbon dioxide during CPR were similar between groups., Conclusions: In this prospective study of pediatric IHCA, pre-existing PH was present in 16% of children. Pre-arrest PH diagnosis was not associated with statistically significant differences in survival outcomes or intra-arrest physiologic measures., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Financial support for this project was provided through the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD049934, UG1HD049981, UG1HD049983, UG1HD050096, UG1HD063108, UG1HD083166, UG1HD083170, and UG1HD083171) and National Heart, Lung, and Blood Institute (R01HL131544, R01HL147616, K23HL148541, and K23HL153759) and by the Children’s Hospital of Philadelphia Resuscitation Science Center and Department of Anesthesiology and Critical Care Medicine., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Racial and ethnic disparities in resource use among children with CHD remain understudied. We sought to evaluate associations between race, ethnicity, and resource utilisation in children with CHD., Materials and Methods: Annual data from the National Health Interview Survey were collected for years 2010-2018. Children with self-reported CHD and Non-Hispanic White race, Non-Hispanic Black race, or Hispanic ethnicity were identified. Resource use in the preceding year was identified with four measures: primary place of care visited when sick, receiving well-child checkups, number of emergency department visits, and number of office visits. Cohort characteristics were compared across racial and ethnic groups using Kruskal-Wallis and Fisher's exact tests. Multivariable logistic regression was used to determine the association of race and ethnicity with likelihood of having an emergency department visit., Results: We identified 209 children for the primary analysis. Non-Hispanic Black children had significantly more emergency department visits in the prior year, with 11.1% having ≥6 emergency department visits compared to 0.7% and 5.6% of Non-Hispanic White and Hispanic children. Further, 35.2% of Hispanic children primarily received care at clinics/health centres, compared to 17% of Non-Hispanic White children and 11.1% of Non-Hispanic Black children (p = 0.03). On multivariable analysis, Black race was associated with higher odds of emergency department visit compared to White race (odds ratio = 4.19, 95% confidence interval = 1.35 to 13.04, p = 0.01)., Conclusion: In a nationally comprehensive, contemporary cohort of children with CHD, there were some significant racial and ethnic disparities in resource utilisation. Further work is needed to consider the role of socio-economics and insurance status in perpetuating these disparities.

Right ventricular (RV) dysfunction early after tetralogy of Fallot (TOF) increases post-operative morbidity. We investigated associations of circulating biomarkers and socioeconomic factors with early post-operative RV systolic function. Single-center prospective cohort study of infants undergoing TOF repair. Six serologic biomarkers of myocardial fibrosis and wall stress collected at the time of surgery were measured with immunoassay. Geocoding was performed for socioeconomic factors. Multivariate adaptive regression splines (MARS) models identified factors associated with RV function parameters: fractional area change (FAC), global longitudinal strain and strain rate, and free wall strain and strain rate. Seventy-one patients aged 3.5 months (IQR 2.4, 5.2) were included. Galectin-3 was the highest ranked predictor for FAC, global longitudinal strain, and free wall strain, and procollagen type-I carboxy-terminal propeptide (PICP) was the highest ranked predictor for global longitudinal strain rate and free wall strain rate. Several neighborhood characteristics were also highly ranked. Models adjusted R 2 ranged from 0.71 to 0.85 (FAC, global longitudinal strain/strain rate), and 0.55-0.57 (RV free wall strain/strain rate). A combination of serologic biomarkers, socioeconomic, and clinical variables explain a significant proportion of the variability in RV function after TOF repair. These factors may inform pre-operative risk-stratification for these patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To evaluate associations between calcium administration and outcomes among children with in-hospital cardiac arrest and among specific subgroups in which calcium use is hypothesized to provide clinical benefit., Methods: This is a secondary analysis of observational data collected prospectively as part of the ICU-RESUScitation project. Children 37 weeks post-conceptual age to 18 years who received chest compressions in one of 18 intensive care units from October 2016-March 2021 were eligible. Data included child and event characteristics, pre-arrest laboratory values, pre- and intra-arrest haemodynamics, and outcomes. Outcomes included sustained return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with favourable neurologic outcome. A propensity score weighted cohort was used to evaluate associations between calcium use and outcomes. Subgroups included neonates, and children with hyperkalaemia, sepsis, renal insufficiency, cardiac surgery with cardiopulmonary bypass, and calcium-avid cardiac diagnoses., Results: Of 1,100 in-hospital cardiac arrests, median age was 0.63 years (IQR 0.19, 3.81); 450 (41%) received calcium. Among the weighted cohort, calcium use was not associated with sustained ROSC (aOR, 0.87; CI95 0.61-1.24; p = 0.445), but was associated with lower rates of both survival to hospital discharge (aOR, 0.68; CI95 0.52-0.89; p = 0.005) and survival with favourable neurologic outcome at hospital discharge (aOR, 0.75; CI95 0.57-0.98; p = 0.038). Among subgroups, calcium use was associated with lower rates of survival to hospital discharge in children with sepsis and renal insufficiency., Conclusions: Calcium use was common during paediatric in-hospital cardiac arrest and associated with worse outcomes at hospital discharge., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Epinephrine is provided during cardiopulmonary resuscitation (CPR) to increase systemic vascular resistance and generate higher diastolic blood pressure (DBP) to improve coronary perfusion and attain return of spontaneous circulation (ROSC). The DBP response to epinephrine during pediatric CPR and its association with outcomes have not been well described. Thus, the objective of this study was to measure the association between change in DBP after epinephrine administration during CPR and ROSC., Methods: This was a prospective multicenter study of children receiving ≥ 1 min of CPR with ≥ 1 dose of epinephrine and evaluable invasive arterial BP data in the 18 ICUs of the ICU-RESUS trial (NCT02837497). Blood pressure waveforms underwent compression-by-compression quantitative analysis. The mean DBP before first epinephrine dose was compared to mean DBP two minutes post-epinephrine. Patients with ≥ 5 mmHg increase in DBP were characterized as "responders.", Results: Among 147 patients meeting inclusion criteria, 66 (45%) were characterized as responders and 81 (55%) were non-responders. The mean increase in DBP with epinephrine was 4.4 [- 1.9, 11.5] mmHg (responders: 13.6 [7.5, 29.3] mmHg versus non-responders: - 1.5 [- 5.0, 1.5] mmHg; p < 0.001). After controlling for a priori selected covariates, epinephrine response was associated with ROSC (aRR 1.60 [1.21, 2.12]; p = 0.001). Sensitivity analyses identified similar associations between DBP response thresholds of ≥ 10, 15, and 20 mmHg and ROSC; DBP responses of ≥ 10 and ≥ 15 mmHg were associated with higher aRR of survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score of 1-3 or no worsening from baseline)., Conclusions: The change in DBP following epinephrine administration during pediatric in-hospital CPR was associated with return of spontaneous circulation., (© 2023. The Author(s).)

The design and conduct of pediatric sedation studies in critically ill patients have historically been challenging due to the complexity of the pediatric intensive care unit (PICU) environment and the difficulty of establishing equipoise. Clinical trials, for instance, represent 1 important means of advancing our knowledge in this field, but there is a paucity of such studies in the literature. Accounting for ground-level factors in planning for each trial phase (eg, enrollment, intervention, assessment, and follow-up) and the presence of broader system limitations is of key importance. In addition, there is a need for early planning, coordination, and obtaining buy-in from individual study sites and staff to ensure success, particularly for multicenter studies. This review synthesizes the current state of pediatric sedation research and the myriad of challenges in designing and conducting successful trials in this particular area. The review poses consideration for future research directions, including novel study designs, and discusses electroencephalography monitoring and neurodevelopmental outcomes of PICU survivors., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort., Design: Prospective observational study., Setting: Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020., Patients: Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR., Interventions: None., Measurements and Main Results: Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051)., Conclusions: These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR., Competing Interests: Drs. Berg, Morgan, Reeder, Bell, Carcillo, Carpenter, Dean, Fink, Hall, McQuillen, Meert, Mourani, Pollack, Sapru, Wessel, Wolfe, Yates, Zuppa, and Sutton received National Institutes of Health (NIH) grant funding to their institution related to this project. Drs. Berg’s and Sutton’s institutions received funding from the National Heart, Lung, and Blood Institute (NHLBI). Drs. Berg’s, Horvat’s, McQuillen’s, Sapru’s, Schneiter’s, and Zuppa’s institutions received funding from the National Institute of Child Health and Human Development (NICHD). Drs. Berg, Morgan, Reeder, Bell, Carcillo, Carpenter, Dean, Fink, Franzon, Frazier, Friess, Hall, Horvat, Manga, McQuillen, Meert, Mourani, Naim, Pollack, Sapru, Schneiter, Wessel, Wolfe, Yates, and Sutton received support for article research from the NIH. Dr. Morgan’s institution received funding from the NHLBI (K23HL148541). Drs. Reeder’s, Bell’s, Carcillo’s, Carpenter’s, Dean’s, Fink’s, Frazier’s, Friess’s, Hall’s, Manga’s, Meert’s, Mourani’s, Nadkarni’s, Naim’s, Pollack’s, Wessel’s, Wolfe’s, and Yates’ institutions received funding from the NIH. Dr. Fink’s institution received funding from the Neurocritical Care Society; she received funding from the Child Neurology Society. Drs. Fink and Hall received funding from the American Board of Pediatrics. Dr. Hall received funding from Abbvie and Kiadis. Dr. Maa’s institution received funding from the Children’s Hospital of Philadelphia, the NHBLI (R01HL131544), and the NICHD (U01HD049934, UG1HD049981, UG1HD049983, UG1HD050096, UG1HD063108, UG1HD083166, UG1HD083170, and UG1HD083171). Dr. Nadkarni’s institution received funding from Zoll Medical, the American Heart Association RQI Partners, and Nihon-Kohden; he disclosed that he is the Society of Critical Care Medicine President elect Citizen. CPR Foundation Board member volunteer, and an International Liaison Committee on Resuscitation board member volunteer. Dr. Notterman received funding from GenoTwin SAB. Dr. Sutton disclosed that he is the Chair of the Pediatric Research Task Force of the American Heart Association’s Get with the Guidelines Resuscitation National Registry and a Pediatric Advanced Life Support author. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: The COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes., Design: Multicenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021)., Setting: Data source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial., Patients: Children (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS., Interventions: None., Measurements and Main Results: Among 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46]; p = 0.04)., Conclusions: Using the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors., Competing Interests: Drs. Morgan, Wolfe, Reeder, Alvey, Frazier, Friess, Maa, McQuillen, Meert, Yates, Bell, Burns, Carcillo, Carpenter, Dean, Fink, Franzon, Hall, Horvat, Manga, Mourani, Naim, Pollack, Sapru, Wessel, Zuppa, and Sutton received support for article research from the National Institutes of Health (NIH). Drs. Wolfe, Reeder, Alvey, Frazier, Friess, Meert, Yates, Carpenter, Dean, Fink, Hall, Manga, Mourani, Naim, Pollack, Sapru, and Zuppa’s institutions received funding from the NIH. Dr. Wolfe received funding from The Debriefing Academy and Zoll. Drs. Maa, Carcillo, and Sutton’s institutions received funding from the National Heart, Lung, and Blood Institute. Drs. Maa’s, McQuillen’s, Bell’s, Carcillo’s, and Horvat’s institutions received funding from the National Institute of Child Health and Human Development. Dr. Carcillo’s institution received funding from the National Institute of General Medical Sciences. Dr. Fink’s institution received funding from the Neurocritical Care Society; she received funding from the American Board of Pediatrics. Dr. Franzon received funding from the Health Navigator Foundation. Dr. Hall received funding fom La Jolla Pharmaceuticals, Abbvie, and Kiadis. Dr. Hall reports grant funding from the NIH, serving as a consultant for LaJolla Pharmaceuticals (service on a data safety and monitoring board [DSMB]) and Abbvie (service on a DSMB), and licensing income from Kiadis. Dr. Pollack reports grant funding from the NIH and from Mallinckrodt Pharmaceuticals, LLC. Dr. Tilford disclosed that he is an employee of Central Michigan University and University Pediatricians. Dr. Wessel’s institution received funding from the Children’s Hospital of Philadelphia; he received funding from the NIH. Dr. Sutton disclosed that he is the chair of the Pediatric Research Task Force of the American Heart Association’s Get with the Guidelines-Resuscitation Registry. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To evaluate associations between sodium bicarbonate use and outcomes during pediatric in-hospital cardiac arrest (p-IHCA)., Design: Prespecified secondary analysis of a prospective, multicenter cluster randomized interventional trial., Setting: Eighteen participating ICUs of the ICU-RESUScitation Project (NCT02837497)., Patients: Children less than or equal to 18 years old and greater than or equal to 37 weeks post conceptual age who received chest compressions of any duration from October 2016 to March 2021., Interventions: None., Measurements and Main Results: Child and event characteristics, prearrest laboratory values (2-6 hr prior to p-IHCA), pre- and intraarrest hemodynamics, and outcomes were collected. In a propensity score weighted cohort, the relationships between sodium bicarbonate use and outcomes were assessed. The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Of 1,100 index cardiopulmonary resuscitation events, median age was 0.63 years (interquartile range, 0.19-3.81 yr); 528 (48.0%) received sodium bicarbonate; 773 (70.3%) achieved ROSC; 642 (58.4%) survived to hospital discharge; and 596 (54.2%) survived to hospital discharge with favorable neurologic outcome. Among the weighted cohort, sodium bicarbonate use was associated with lower survival to hospital discharge rate (adjusted odds ratio [aOR], 0.7; 95% CI, 0.54-0.92; p = 0.01) and lower survival to hospital discharge with favorable neurologic outcome rate (aOR, 0.69; 95% CI, 0.53-0.91; p = 0.007). Sodium bicarbonate use was not associated with ROSC (aOR, 0.91; 95% CI, 0.62-1.34; p = 0.621)., Conclusions: In this propensity weighted multicenter cohort study of p-IHCA, sodium bicarbonate use was common and associated with lower rates of survival to hospital discharge., Competing Interests: Drs. Reeder’s, Carcillo’s, Carpenter’s, Dean’s, Fink’s, Frazier’s, Friess’, Hall’s, Manga’s, Morgan’s, Mourani’s, Nadkarni’s, Naim’s, Palmer’s, Pollack’s, Wessel’s, Wolfe’s, Yates’, Zuppa’s, Sutton’s, and Meert’s institutions received funding from the National Institutes of Health (NIH). Drs. Reeder, Berg, Carcillo, Carpenter, Dean, Fink, Frazier, Friess, Hall, Horvat, Maa, McQuillen, Morgan, Mourani, Nadkarni, Naim, Palmer, Pollack, Wessel, Wolfe, Yates, Zuppa, and Meert received support for article research from the NIH. Dr. Berg’s institution received funding from the National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network grant and the National Heart, Lung, and Blood Institute (NHLBI) ICU-RESUS trial grant. Dr. Fink’s institution received funding from the Neurocritical Care Society; she received funding from the American Board of Pediatrics and the Child Neurology Society. Dr. Friess received funding from an expert witness testimony. Dr. Hall received funding from Abbvie, La Jolla Pharmaceuticals, and Kiadis. Drs. Horvat, Maa, and McQuillen’s institutions received funding from the NICHD. Dr. Horvat’s institution received funding from the National Institute of Neurological Disorders and Stroke. Dr. Maa’s institution received funding from the NHLBI. Dr. Mourani disclosed the off-label product use of sodium bicarbonate. Dr. Pollack disclosed work for hire. Dr. Wolfe received funding from The Debriefing Academy and Zoll. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To develop and evaluate a high-dimensional, data-driven model to identify patients at high risk of clinical deterioration from routinely collected electronic health record (EHR) data., Materials and Methods: In this single-center, retrospective cohort study, 488 patients with single-ventricle and shunt-dependent congenital heart disease <6 months old were admitted to the cardiac intensive care unit before stage 2 palliation between 2014 and 2019. Using machine-learning techniques, we developed the Intensive care Warning Index (I-WIN), which systematically assessed 1028 regularly collected EHR variables (vital signs, medications, laboratory tests, and diagnoses) to identify patients in the cardiac intensive care unit at elevated risk of clinical deterioration. An ensemble of 5 extreme gradient boosting models was developed and validated on 203 cases (130 emergent endotracheal intubations, 34 cardiac arrests requiring cardiopulmonary resuscitation, 10 extracorporeal membrane oxygenation cannulations, and 29 cardiac arrests requiring cardiopulmonary resuscitation onto extracorporeal membrane oxygenation) and 378 control periods from 446 patients., Results: At 4 hours before deterioration, the model achieved an area under the receiver operating characteristic curve of 0.92 (95% confidence interval, 0.84-0.98), 0.881 sensitivity, 0.776 positive predictive value, 0.862 specificity, and 0.571 Brier skill score. Performance remained high at 8 hours before deterioration with 0.815 (0.688-0.921) area under the receiver operating characteristic curve., Conclusions: I-WIN accurately predicted deterioration events in critically-ill infants with high-risk congenital heart disease up to 8 hours before deterioration, potentially allowing clinicians to target interventions. We propose a paradigm shift from conventional expert consensus-based selection of risk factors to a data-driven, machine-learning methodology for risk prediction. With the increased availability of data capture in EHRs, I-WIN can be extended to broader applications in data-rich environments in critical care., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Aim: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge., Methods: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020. Eligible patients had ≥30 s of rSO2 data recorded during CPR. We compared median rSO2 and percentage of rSO2 measurements above a priori thresholds for the entire event and the final five minutes of the CPR event between patients with and without ROSC and survival to discharge., Results: Twenty-one patients with 23 CPR events were analyzed. ROSC was achieved in 17/23 (73.9%) events and five/21 (23.8%) patients survived to discharge. The median rSO2 was higher for events with ROSC vs. no ROSC for the overall event (62% [56%, 70%] vs. 45% [35%, 51%], p = 0.025) and for the final 5 minutes of the event (66% [55%, 72%] vs. 43% [35%, 44%], p = 0.01). Patients with ROSC had a higher percentage of measurements above 50% during the final five minutes of CPR (100% [100%, 100%] vs. 0% [0%, 29%], p = 0.01). There was no association between rSO2 and survival to discharge., Conclusions: Higher cerebral rSO2 during CPR for pediatric cardiac arrest was associated with higher rates of ROSC but not with survival to discharge., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Importance: Approximately 40% of children who experience an in-hospital cardiac arrest survive to hospital discharge. Achieving threshold intra-arrest diastolic blood pressure (BP) targets during cardiopulmonary resuscitation (CPR) and systolic BP targets after the return of circulation may be associated with improved outcomes., Objective: To evaluate the effectiveness of a bundled intervention comprising physiologically focused CPR training at the point of care and structured clinical event debriefings., Design, Setting, and Participants: A parallel, hybrid stepped-wedge, cluster randomized trial (Improving Outcomes from Pediatric Cardiac Arrest-the ICU-Resuscitation Project [ICU-RESUS]) involving 18 pediatric intensive care units (ICUs) from 10 clinical sites in the US. In this hybrid trial, 2 clinical sites were randomized to remain in the intervention group and 2 in the control group for the duration of the study, and 6 were randomized to transition from the control condition to the intervention in a stepped-wedge fashion. The index (first) CPR events of 1129 pediatric ICU patients were included between October 1, 2016, and March 31, 2021, and were followed up to hospital discharge (final follow-up was April 30, 2021)., Intervention: During the intervention period (n = 526 patients), a 2-part ICU resuscitation quality improvement bundle was implemented, consisting of CPR training at the point of care on a manikin (48 trainings/unit per month) and structured physiologically focused debriefings of cardiac arrest events (1 debriefing/unit per month). The control period (n = 548 patients) consisted of usual pediatric ICU management of cardiac arrest., Main Outcomes and Measures: The primary outcome was survival to hospital discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1 to 3 or no change from baseline (score range, 1 [normal] to 6 [brain death or death]). The secondary outcome was survival to hospital discharge., Results: Among 1389 cardiac arrests experienced by 1276 patients, 1129 index CPR events (median patient age, 0.6 [IQR, 0.2-3.8] years; 499 girls [44%]) were included and 1074 were analyzed in the primary analysis. There was no significant difference in the primary outcome of survival to hospital discharge with favorable neurologic outcomes in the intervention group (53.8%) vs control (52.4%); risk difference (RD), 3.2% (95% CI, -4.6% to 11.4%); adjusted OR, 1.08 (95% CI, 0.76 to 1.53). There was also no significant difference in survival to hospital discharge in the intervention group (58.0%) vs control group (56.8%); RD, 1.6% (95% CI, -6.2% to 9.7%); adjusted OR, 1.03 (95% CI, 0.73 to 1.47)., Conclusions and Relevance: In this randomized clinical trial conducted in 18 pediatric intensive care units, a bundled intervention of cardiopulmonary resuscitation training at the point of care and physiologically focused structured debriefing, compared with usual care, did not significantly improve patient survival to hospital discharge with favorable neurologic outcome among pediatric patients who experienced cardiac arrest in the ICU., Trial Registration: ClinicalTrials.gov Identifier: NCT02837497.

Background: Cefepime is a first-line therapy for Gram-negative infections in children on extracorporeal membrane oxygenation. Cefepime pharmacokinetics (PK) in children on extracorporeal membrane oxygenation still needs to be better established., Methods: This was a prospective single-center PK study. A maximum of 12 PK samples per patient were collected in children <18 years old on extracorporeal membrane oxygenation who received clinically indicated cefepime. External validation of a previously published population PK model was performed by applying the model in a new data set. The predictive performance of the model was determined by calculating prediction errors. Because of poor predictive performance, a revised model was developed using NONMEM and a combined data set that included data from both studies. Dose-exposure simulations were performed using the final model. Optimal dosing was judged based on the ability to maintain free cefepime concentrations above the minimal inhibitory concentration (MIC) for 68% and 100% of the dosing interval., Results: Seventeen children contributed 105 PK samples. The mean (95% CI) and median (interquartile range) prediction errors were 33.7% (19.8-47.7) and 17.5% (-22.6 to 74.4). A combined data set was created, which included 33 children contributing 310 PK samples. The final improved 2-compartment model included weight and serum creatinine on clearance and oxygenator day and blood transfusion on volume of the central compartment. At an MIC of 8 mg/L, 50 mg/kg/dose every 8 hours reached target concentrations., Conclusions: Dosing intervals of 8 hours were needed to reach adequate concentrations at an MIC of 8 mg/L. Longer dosing intervals were adequate with higher serum creatinine and lower MICs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare outcomes between low birth weight (LBW; <2.5 kg) and standard birth weight neonates undergoing cardiac surgery., Study Design: A single-center retrospective study of neonates undergoing cardiac surgery with cardiopulmonary bypass from 2012 to 2018. LBW neonates were 1:2 propensity score-matched to standard birth weight neonates (n = 93 to n = 186) using clinical characteristics. The primary and secondary outcomes were survival to hospital discharge and postoperative complications, respectively. After matching, regression analyses were conducted to compare outcomes., Results: The LBW group had a higher proportion of premature neonates than the standard birth weight group (60% vs 8%; P < .01) and were less likely to survive to hospital discharge (88% vs 95%; OR, 0.39; 95% CI, 0.15-0.97). There was no difference in unplanned cardiac reoperations or catheter-based interventions, cardiac arrest, extracorporeal membrane oxygenation, infection, and end-organ complications between the groups. Among LBW infants, survival was improved at weight >2 kg., Conclusions: LBW is a risk factor for decreased survival. LBW neonates weighing >2 kg have survival comparable to those weighing >2.5 kg., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To conduct a scoping review of sedation clinical trials in the paediatric intensive care setting and summarise key methodological elements., Design: Scoping review., Data Sources: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature and grey references including ClinicalTrials.gov from database inception to 3 August 2021., Study Selection: All human trials in the English language related to sedation in paediatric critically ill patients were included. After title and abstract screening, full-text review was performed. 29 trials were eligible for final analysis., Data Extraction: A coding manual was developed and pretested. Trial characteristics were double extracted., Results: The majority of trials were single centre (22/29, 75.9%), parallel group superiority (17/29, 58.6%), double-blinded (18/29, 62.1%) and conducted in an academic setting (29/29, 100.0%). Trial enrolment (≥90% planned sample size) was achieved in 65.5% of trials (19/29), and retention (≥90% enrolled subjects) in 72.4% of trials (21/29). Protocol violations were reported in nine trials (31.0%). The most commonly studied cohorts were mechanically ventilated patients (28/29, 96.6%) and postsurgical patients (11/29, 37.9%) with inclusion criteria for age ranging from 0±0.5 to 15.0±7.3 years (median±IQR). The median age of enrolled patients was 1.7 years (IQR=4.4 years). Patients excluded from trials were those with neurological impairment (21/29, 72.4%), complex disease (20/29, 69.0%) or receipt of neuromuscular blockade (10/29, 34.5%). Trials evaluated drugs/protocols for sedation management (20/29, 69.0%), weaning (3/29, 10.3%), daily interruption (3/29, 10.3%) or protocolisation (3/29, 10.3%). Primary outcome measures were heterogeneous, as were assessment instruments and follow-up durations., Conclusions: There is substantial heterogeneity in methodological approach in clinical trials evaluating sedation in critically ill paediatric patients. These results provide a basis for the design of future clinical trials to improve the quality of trial data and aid in the development of sedation-related clinical guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are conflicting data regarding the benefit of compression-only bystander cardiopulmonary resuscitation (CO-CPR) compared with CPR with rescue breathing (RB-CPR) after pediatric out-of-hospital cardiac arrest (OHCA)., Objectives: This study sought to test the hypothesis that RB-CPR is associated with improved neurologically favorable survival compared with CO-CPR following pediatric OHCA, and to characterize age-stratified outcomes with CPR type compared with no bystander CPR (NO-CPR)., Methods: Analysis of the CARES registry (Cardiac Arrest Registry to Enhance Survival) for nontraumatic pediatric OHCAs (patients aged ≤18 years) from 2013-2019 was performed. Age groups included infants (<1 year), children (1 to 11 years), and adolescents (≥12 years). The primary outcome was neurologically favorable survival at hospital discharge., Results: Of 13,060 pediatric OHCAs, 46.5% received bystander CPR. CO-CPR was the most common bystander CPR type. In the overall cohort, neurologically favorable survival was associated with RB-CPR (adjusted OR: 2.16; 95% CI: 1.78-2.62) and CO-CPR (adjusted OR: 1.61; 95% CI: 1.34-1.94) compared with NO-CPR. RB-CPR was associated with a higher odds of neurologically favorable survival compared with CO-CPR (adjusted OR: 1.36; 95% CI: 1.10-1.68). In age-stratified analysis, RB-CPR was associated with better neurologically favorable survival versus NO-CPR in all age groups. CO-CPR was associated with better neurologically favorable survival compared with NO-CPR in children and adolescents, but not in infants., Conclusions: CO-CPR was the most common type of bystander CPR in pediatric OHCA. RB-CPR was associated with better outcomes compared with CO-CPR. These results support present guidelines for RB-CPR as the preferred CPR modality for pediatric OHCA., Competing Interests: Funding Support and Author Disclosures The Cardiac Arrest Registry to Enhance Survival was funded by the United States Centers for Disease Control and Prevention from 2004 to 2012. The program is now supported through private funding from the American Red Cross, the American Heart Association, and in-kind support from Stryker Corporation and Emory University. At present, the Centers for Disease Control and Prevention provide technical support and expertise for the program. This work was also supported by the Cardiac Center Clinical Research Core at Children’s Hospital of Philadelphia and the Scientific Advisory of the American Red Cross. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Tetralogy of Fallot (TOF) repair is associated with excellent operative survival. However, a subset of patients experiences post-operative complications, which can significantly alter the early and late post-operative course. We utilized a machine learning approach to identify risk factors for post-operative complications after TOF repair. Methods: We conducted a single-center prospective cohort study of children <2 years of age with TOF undergoing surgical repair. The outcome was occurrence of post-operative cardiac complications, measured between TOF repair and hospital discharge or death. Predictors included patient, operative, and echocardiographic variables, including pre-operative right ventricular strain and fractional area change as measures of right ventricular function. Gradient-boosted quantile regression models (GBM) determined predictors of post-operative complications. Cross-validated GBMs were implemented with and without a filtering stage non-parametric regression model to select a subset of clinically meaningful predictors. Sensitivity analysis with gradient-boosted Poisson regression models was used to examine if the same predictors were identified in the subset of patients with at least one complication. Results: Of the 162 subjects enrolled between March 2012 and May 2018, 43 (26.5%) had at least one post-operative cardiac complication. The most frequent complications were arrhythmia requiring treatment ( N = 22, 13.6%), cardiac catheterization ( N = 17, 10.5%), and extracorporeal membrane oxygenation (ECMO) ( N = 11, 6.8%). Fifty-six variables were used in the machine learning analysis, of which there were 21 predictors that were already identified from the first-stage regression. Duration of cardiopulmonary bypass (CPB) was the highest ranked predictor in all models. Other predictors included gestational age, pre-operative right ventricular (RV) global longitudinal strain, pulmonary valve Z-score, and immediate post-operative arterial oxygen level. Sensitivity analysis identified similar predictors, confirming the robustness of these findings across models. Conclusions: Cardiac complications after TOF repair are prevalent in a quarter of patients. A prolonged surgery remains an important predictor of post-operative complications; however, other perioperative factors are likewise important, including pre-operative right ventricular remodeling. This study identifies potential opportunities to optimize the surgical repair for TOF to diminish post-operative complications and secure improved clinical outcomes. Efforts toward optimizing pre-operative ventricular remodeling might mitigate post-operative complications and help reduce future morbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Faerber, Huang, Zhang, Song, DeCost, Mascio, Ravishankar, O'Byrne, Naim, Kawut, Goldmuntz and Mercer-Rosa.)

Background: Electroencephalographic seizures (ESs) after neonatal cardiac surgery are often subclinical and have been associated with poor outcomes. An accurate ES prediction model could allow targeted continuous electroencephalographic monitoring (CEEG) for high-risk neonates., Methods: ES prediction models were developed and validated in a multicenter prospective cohort where all postoperative neonates who underwent cardiopulmonary bypass (CPB) also underwent CEEG., Results: ESs occurred in 7.4% of neonates (78 of 1053). Model predictors included gestational age, head circumference, single-ventricle defect, deep hypothermic circulatory arrest duration, cardiac arrest, nitric oxide, extracorporeal membrane oxygenation, and delayed sternal closure. The model performed well in the derivation cohort (c-statistic, 0.77; Hosmer-Lemeshow, P = .56), with a net benefit (NB) over monitoring all and none over a threshold probability of 2% in decision curve analysis (DCA). The model had good calibration in the validation cohort (Hosmer-Lemeshow, P = .60); however, discrimination was poor (c-statistic, 0.61), and in DCA there was no NB of the prediction model between the threshold probabilities of 8% and 18%. By using a cut point that emphasized negative predictive value in the derivation cohort, 32% (236 of 737) of neonates would not undergo CEEG, including 3.5% (2 of 58) of neonates with ESs (negative predictive value, 99%; sensitivity, 97%)., Conclusions: In this large prospective cohort, a prediction model of ESs in neonates after CPB had good performance in the derivation cohort, with an NB in DCA. However, performance in the validation cohort was weak, with poor discrimination, poor calibration, and no NB in DCA. These findings support CEEG of all neonates after CPB., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to describe the pharmacokinetics (PK) of intravenous phenobarbital in neonates and infants on extracorporeal membrane oxygenation (ECMO) and to provide dosing recommendations in this population. We performed a retrospective single-center PK study of phenobarbital in neonates and infants on ECMO between January 1, 2014, and December 31, 2018. We developed a population PK model using nonlinear mixed-effects modeling, performed simulations using the final PK parameters, and determined optimal dosing based on attainment of peak and trough concentrations between 20 and 40 mg/L. We included 35 subjects with a median (range) age and weight of 14 days (1-154 days) and 3.4 kg (1.6-8.1 kg), respectively. A total of 194 samples were included in the analysis. Five children (14%) contributing 30 samples (16%) were supported by continuous venovenous hemodiafiltration (CVVHDF). A 1-compartment model best described the data. Typical clearance and volume of distribution for a 3.4-kg infant were 0.038 L/h and 3.83 L, respectively. Clearance increased with age and CVVHDF. Although on ECMO, phenobarbital clearance in children on CVVHDF was 6-fold higher than clearance in children without CVVHDF. In typical subjects, a loading dose of 30 mg/kg/dose followed by maintenance doses of 6-7 mg/kg/day administered as divided doses every 12 hours reached goal concentrations. Age did not impact dosing recommendations. However, higher doses were needed in children on CVVHDF. We strongly recommend therapeutic drug monitoring in children on renal replacement therapy (excluding slow continuous ultrafiltration) while on ECMO., (© 2020, The American College of Clinical Pharmacology.)