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Objective:  The purpose of the study was to determine if antegrade continence enema (ACE) alone is an effective treatment for patients with severe functional constipation and segmental colonic dysmotility., Methods:  A retrospective study of patients with functional constipation and segmental colonic dysmotility who underwent ACE as their initial means of management. Data was collected from six participating sites in the Pediatric Colorectal and Pelvic Learning Consortium. Patients who had a colonic resection at the same time as an ACE or previously were excluded from analysis. Only patients who were 21 years old or younger and had at least 1-year follow-up after ACE were included. All patients had segmental colonic dysmotility documented by colonic manometry. Patient characteristics including preoperative colonic and anorectal manometry were summarized, and associations with colonic resection following ACE were evaluated using Fisher's exact test and Wilcoxon rank-sum test. p -Values of less than 0.05 were considered significant. Statistical analyses and summaries were performed using SAS version 9.4 (SAS Institute Inc., Cary, North Carolina, United States)., Results:  A total of 104 patients from 6 institutions were included in the study with an even gender distribution (males n  = 50, 48.1%) and a median age of 9.6 years (interquartile range 7.4, 12.8). At 1-year follow-up, 96 patients (92%) were successfully managed with ACE alone and 8 patients (7%) underwent subsequent colonic resection for persistent symptoms. Behavioral disorder, type of bowel management, and the need for botulinum toxin administered to the anal sphincters was not associated with the need for subsequent colonic resection. On anorectal manometry, lack of pelvic floor dyssynergia was significantly associated with the need for subsequent colonic resection; 3/8, 37.5% without pelvic dyssynergia versus 1/8, 12.5% ( p  = 0.023) with pelvic dyssynergia underwent subsequent colonic resection., Conclusion:  In patients with severe functional constipation and documented segmental colonic dysmotility, ACE alone is an effective treatment modality at 1-year follow-up. Patients without pelvic floor dyssynergia on anorectal manometry are more likely to receive colonic resection after ACE. The vast majority of such patients can avoid a colonic resection., Competing Interests: None declared., (Thieme. 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).)

Importance: Patients with underlying cardiac disease form a considerable proportion of pediatric patients who experience in-hospital cardiac arrest. In pediatric patients after cardiac surgery, CPR with abdominal compressions alone (AC-CPR) may provide an alternative to standard chest compression CPR (S-CPR) with additional procedural and physiologic advantages., Objective: Quantitatively describe hemodynamics during cardiopulmonary resuscitation (CPR) and outcomes of infants who received only abdominal compressions (AC-CPR)., Design: This is a sub-group analysis of the prospective, observational cohort from the ICU-RESUS trial NCT028374497., Setting & Patients: A single site quaternary care pediatric cardiothoracic intensive care unit enrolled in the ICU-RESUS trial. Patients less than 1 year of age with congenital heart disease who required compressions during cardiac arrest., Interventions: Use of AC-CPR during cardiac arrest resuscitation., Measurements and Main Results: Invasive arterial line waveforms during CPR were analyzed for 11 patients (10 surgical cardiac and 1 medical cardiac). Median weight was 3.3 kg [IQR 3.0, 4.0]; and median duration of CPR was 5.0 [3.0, 20.0] minutes. Systolic (median 57 [IQR 48, 65] mmHg) and diastolic (median 32 [IQR 24, 43] mmHg) blood pressures were achieved with a median rate of 114 [IQR 100, 124] compressions per minute. Return of spontaneous circulation was obtained in 9 of 11 (82%) patients; 2 patients (18%) were cannulated for extracorporeal cardiopulmonary resuscitation (ECPR) and 6 (55%) survived to hospital discharge with favorable neurologic outcome., Conclusions: AC-CPR may offer an alternative method to maintain perfusion for infants who experience cardiac arrest. This may have particular benefit in pediatric patients after cardiac surgery for whom external chest compressions may be harmful due to anatomic and physiologic considerations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Richard P. Fernandez, MD reports financial support, administrative support, and statistical analysis were provided by National Institute of Child Health and Human Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: Social determinants of health (SDOH) are associated with disparities in disease severity and in-hospital outcomes among critically ill children. It is unknown whether SDOH are associated with later outcomes. We evaluated associations between SDOH measures and mortality, new functional morbidity, and health-related quality of life (HRQL) decline among children surviving septic shock., Design: Secondary analysis of the Life After Pediatric Sepsis Evaluation (LAPSE) prospective cohort study was conducted between 2014 and 2017., Setting: Twelve academic U.S. PICUs were involved in the study., Patients: Children younger than 18 years with community-acquired septic shock were involved in the study., Interventions: None., Measurements and Main Results: We assessed associations between race, ethnicity, income, education, marital status, insurance, language, and home U.S. postal code with day 28 mortality, new functional morbidity at discharge per day 28, and HRQL decline using logistic regression. Of 389 patients, 32% ( n = 98) of families had household income less than $50,000 per year. Median Pediatric Risk of Mortality (PRISM) score was 11 (interquartile range 6, 17). We found that English language and Area Deprivation Index less than 50th percentile were associated with higher PRISM scores. Mortality was 6.7% ( n = 26), new functional morbidity occurred in 21.8% ( n = 78) of patients, and HRQL decline by greater than 10% occurred in 31.0% of patients ( n = 63). We failed to identify any association between SDOH measures and mortality, new functional morbidity, or HRQL decline. We are unable to exclude the possibility that annual household income greater than or equal to $50,000 was associated with up to 81% lesser odds of mortality and, in survivors, more than three-fold greater odds of HRQL decline by greater than 10%., Conclusions: In this secondary analysis of the 2014-2017 LAPSE dataset, we failed to identify any association between SDOH measures and in-hospital or postdischarge outcomes following pediatric septic shock. This finding may be reflective of the high illness severity and single disease (sepsis) of the cohort, with contribution of clinical factors to functional and HRQL outcomes predominating over prehospital and posthospital SDOH factors., Competing Interests: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) grants R03HD104001 (Dr. Reeder) and K23HD100566 (Dr. Killien). The Life After Pediatric Sepsis Evaluation study was funded by the Eunice Kennedy Shriver NICHD grant R01HD073362, and was supported in part by the following cooperative agreements: UG1HD050096, UG1HD049981, UG1HD049983, UG1HD063108, UG1HD083171, UG1HD083166, UG1HD083170, U10HD050012, U10HD063106, and U01HD049934. Drs. Lenz, Banks, Meert, Zimmerman, and Killien received support for article research from the National Institutes of Health (NIH). Dr. Beckstead received support for article research from the NICHD. Drs. Beckstead and Banks disclosed government funding. Drs. Banks, Zimmerman, and Killien’s institutions received funding from the NICHD. Drs. Reeder and Meert’s institution received funding from the NIH. Dr. Zimmerman’s institution received funding from Immunexpress; he received funding from Elsevier Publishing. Dr. Killien received funding from Immunexpress. 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.)

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.)

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).)

Purpose: Antegrade colonic enemas (ACE) can be an effective management option for defecation disorders and improve quality of life. Best practice regarding channel placement is unclear and variation may exist around preferred initial type of channel, age at placement, and underlying diagnoses. We aimed to describe practice patterns and patient characteristics around ACE channel placement., Methods: We conducted a multicenter retrospective study of children with an ACE channel cared for at sites participating in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) from 2017 to 2022. Kruskal-Wallis test was utilized to test the age at surgery by site with significance level of 0.05., Results: 500 patients with ACE channel were included. 293 (58.6%) patients had their ACE procedure at a PCPLC center. The median age at surgery was 7.6 [IQR 5.3-11.0] years for the overall cohort and 8.1 [IQR 5.3-11.5] years for placement at PCPLC centers. For PCPLC centers, median age at placement varied significantly across centers (p = 0.009). 371 (74.2%) patients received Malone appendicostomy, 116 (23.2%) received cecostomy, and 13 (2.6%) received Neo-Malone appendicostomy. Median age of patients by channel type was 7.7 [IQR 5.3-11.0], 7.5 [IQR 5.7-11.0], and 9.8 [IQR 4.2-11.6] years, respectively. The most common indication for cecostomy was idiopathic/refractory constipation (52.6%), whereas anorectal malformation was the most common indication for Malone (47.2%) and Neo-Malone (61.5%). Among ACE channels placed at PCPLC centers, there was variation across institutions in preferred initial channel type. The 4 highest volume centers favored Malone appendicostomy over cecostomy., Conclusion: There is variation in practice of ACE channel placement. At specialty pediatric colorectal centers, age at time of placement and type of channel placed varied across institutions. Further work is needed to better characterize diagnosis- and age-focused patient centered outcomes to clarify recommendations for our patients who benefit from these procedures., Type of Study: Retrospective comparative study., Level of Evidence: Level III., (Published by Elsevier Inc.)

Purpose: Congenital anorectal stenosis is managed by dilations or operative repair. Recent studies now propose use of dilations as the primary treatment modality to potentially defer or eliminate the need for surgical repair. We aim to characterize the management and outcomes of these patients via a multi-institutional review using the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) registry., Methods: A retrospective database review was performed using the PCPLC registry. The patients were evaluated for demographics, co-morbidities, diagnostic work-up, surgical intervention, current bowel management, and complications., Results: 64 patients with anal or rectal stenosis were identified (57 anal, 7 rectal) from a total of 14 hospital centers. 59.6% (anal) and 42.9% (rectal) were male. The median age was 3.2 (anal) and 1.9 years (rectal). 11 patients with anal stenosis also had Currarino Syndrome with 10 of the 11 patients diagnosed with a presacral mass compared to only one rectal stenosis with Currarino Syndrome and a presacral mass. 13 patients (22.8%, anal) and one (14.3%, rectal) underwent surgical correction. Nine patients (8 anal, 1 rectal) underwent PSARP. Other procedures performed were cutback anoplasty and anterior anorectoplasty. The median age at repair was 8.4 months (anal) and 10 days old (rectal). One patient had a wound complication in the anal stenosis group. Bowel management at last visit showed little differences between groups or treatment approach., Conclusion: The PCPLC registry demonstrated that these patients can often be managed successfully with dilations alone. PSARP is the most common surgical repair chosen for those who undergo surgical repair., Level of Evidence: III., Competing Interests: Conflict of interest Many authors are members of this consortium but have no financial or further competing interests in the outcomes of the study. All other authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.)

Introduction: Swine exhibit cerebral cortex mitochondrial dysfunction and neuropathologic injury after hypoxic cardiac arrest treated with hemodynamic-directed CPR (HD-CPR) despite normal Cerebral Performance Category scores. We analyzed the temporal evolution of plasma protein biomarkers of brain injury and inflammatory cytokines, as well as cerebral cortical mitochondrial injury and neuropathology for five days following pediatric asphyxia-associated cardiac arrest treated with HD-CPR., Methods: One-month-old swine underwent asphyxia associated cardiac arrest, 10-20 min of HD-CPR (goal SBP 90 mmHg, coronary perfusion pressure 20 mmHg), and randomization to post-ROSC survival duration (24, 48, 72, 96, 120 h; n = 3 per group) with standardized post-resuscitation care. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and cytokine levels were collected pre-injury and 1, 6, 24, 48, 72, 96, and 120 h post-ROSC. Cerebral cortical tissue was assessed for: mitochondrial respirometry, mass, and dynamic proteins; oxidative injury; and neuropathology., Results: Relative to pre-arrest baseline (9.4 pg/ml [6.7-12.6]), plasma NfL was increased at all post-ROSC time points. Each sequential NfL measurement through 48 h was greater than the previous value {1 h (12.7 pg/ml [8.4-14.6], p = 0.01), 6 h (30.9 pg/ml [17.7-44.0], p = 0.0004), 24 h (59.4 pg/ml [50.8-96.1], p = 0.0003) and 48 h (85.7 pg/ml [61.9-118.7], p = 0.046)}. Plasma GFAP, inflammatory cytokines or cerebral cortical tissue measurements were not demonstrably different between time points., Conclusions: In a swine model of pediatric cardiac arrest, plasma NfL had an upward trajectory until 48 h post-ROSC after which it remained elevated through five days, suggesting it may be a sensitive marker of neurologic injury following pediatric cardiac arrest., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Julia Slovis currently works for GalaxoSmithKline, but her employment began after completion of her contribution to this manuscript., (© 2024 The Authors.)

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).)

Objective: The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics., Methods: A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores., Results: Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes., Conclusions: Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

Background: Hirschsprung Disease (HD) is a rare cause of functional bowel obstruction in children. Patients are typically diagnosed in the neonatal period and undergo pull-through (PT) soon after diagnosis. The optimal management and post-operative outcomes of children who present in a delayed fashion are unknown., Methods: A multi-center retrospective review of children with HD was performed at participating Pediatric Colorectal and Pelvic Learning Consortium sites. Children were stratified by age at diagnosis (neonates <29 days; infants 29 days-12 months; toddler 1 year-5 years and child >5 years)., Results: 679 patients with HD from 14 sites were included; Most (69%) were diagnosed in the neonatal period. Age at diagnosis was not associated with differences in 30-day complication rates or need for PT revision. Older age at diagnosis was associated with a greater likelihood of undergoing fecal diversion after PT (neonate 10%, infant 12%, toddler 26%, child 28%, P < 0.001) and a greater need for intervention for constipation or incontinence postoperatively (neonate 56%, infant 62%, toddler 78%, child 69%, P < 0.001)., Conclusion: Delayed diagnosis of HD does not impact 30-day post-operative outcomes or need for revision surgery but, delayed diagnosis is associated with increased need for fecal diversion after pull-through., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dietary modification is the mainstay of treatment for postoperative chylothorax in children. However, optimal fat-modified diet (FMD) duration to prevent recurrence is unknown. Our aim was to determine the association between FMD duration and chylothorax recurrence., Methods: Retrospective cohort study conducted across 6 pediatric cardiac intensive care units within the United States. Patients aged <18 years who developed chylothorax within 30 days after cardiac surgery between January 2020 and April 2022 were included. Patients with a Fontan palliation, who died, or were lost to follow-up or within 30 days of resuming a regular diet were excluded. FMD duration was defined as the first day of a FMD when chest tube output was <10 mL/kg/d without increasing until the resumption of a regular diet. Patients were classified into 3 groups (<3 weeks, 3-5 weeks, >5 weeks) based on FMD duration., Results: A total of 105 patients were included: <3 weeks (n = 61) 3-5 weeks (n = 18), and >5 weeks (n = 26). Demographic, surgical, and hospitalization characteristics were not different across groups. In the >5 weeks group, chest tube duration was longer compared with the <3 weeks and 3-5 weeks groups (median, 17.5 days [interquartile range, 9-31] vs 10 and 10.5 days; P = .04). There was no recurrence of chylothorax within 30 days once chylothorax was resolving regardless of FMD duration., Conclusions: FMD duration was not associated with recurrence of chylothorax, suggesting that FMD duration can safely be shortened to at least <3 weeks from time of resolving chylothorax., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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.

Background: Anorectal malformations (ARM) are rare and heterogenous which creates a challenge in conducting research and offering recommendations for best practice. The Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) was formed in 2016 to address this challenge and created a shared national data registry to collect information about pediatric colorectal patients. There has been no external validation of the data collected. We sought to evaluate the database by performing a patient matched analysis comparing 30-day outcomes identified in the PCPLC registry with the NSQIP-P database for patients undergoing surgical repair of ARM., Methods: Patients captured in the PCPLC database from 2016 to 2021 at institutions also participating in NSQIP-P who underwent ARM repair younger than 12 months old were reviewed for 30-day complications. These patients were matched to their NSQIP-P record using their hospital identification number, and records were compared for concordance in identified complications., Results: A total of 591 patient records met inclusion criteria in the PCPLC database. Of these, 180 patients were also reviewed by NSQIP-P. One hundred and fifty-six patient records had no complications recorded. Twenty-four patient records had a complication listed in one or both databases. There was a 91 % concordance rate between databases. When excluding complications not tracked in the PCPLC registry, this agreement improved to 93 %., Conclusion: Including all patients evaluated for this subpopulation, a 91 % concordance rate was observed when comparing PCPLC collected complications to NSQIP-P. Future efforts can focus on further validating the data within the PCPLC for other patient populations., Level of Evidence: V., (Published by Elsevier Inc.)

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.)

Objective: The Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study 1) to determine if a new, better-performing version of the Endoscopic Third Ventriculostomy Success Score (ETVSS) could be developed, 2) to explore the performance characteristics of the original ETVSS in a modern endoscopic third ventriculostomy (ETV) cohort, and 3) to determine if the addition of radiological variables to the ETVSS improved its predictive abilities., Methods: From April 2008 to August 2019, children (corrected age ≤ 17.5 years) who underwent a first-time ETV for hydrocephalus were included in a prospective multicenter HCRN study. All children had at least 6 months of clinical follow-up and were followed since the index ETV in the HCRN Core Data Registry. Children who underwent choroid plexus cauterization were excluded. Outcome (ETV success) was defined as the lack of ETV failure within 6 months of the index procedure. Kaplan-Meier curves were constructed to evaluate time-dependent variables. Multivariable binary logistic models were built to evaluate predictors of ETV success. Model performance was evaluated with Hosmer-Lemeshow and Harrell's C statistics., Results: Seven hundred sixty-one children underwent a first-time ETV. The rate of 6-month ETV success was 76%. The Hosmer-Lemeshow and Harrell's C statistics of the logistic model containing more granular age and etiology categorizations did not differ significantly from a model containing the ETVSS categories. In children ≥ 12 months of age with ETVSSs of 50 or 60, the original ETVSS underestimated success, but this analysis was limited by a small sample size. Fronto-occipital horn ratio (p = 0.37), maximum width of the third ventricle (p = 0.39), and downward concavity of the floor of the third ventricle (p = 0.63) did not predict ETV success. A possible association between the degree of prepontine adhesions on preoperative MRI and ETV success was detected, but this did not reach statistical significance., Conclusions: This modern, multicenter study of ETV success shows that the original ETVSS continues to demonstrate good predictive ability, which was not substantially improved with a new success score. There might be an association between preoperative prepontine adhesions and ETV success, and this needs to be evaluated in a future large prospective study.

Background: Cloacal exstrophy (CE) represents a rare sub-group of anorectal malformations. Traditionally managed with a permanent colostomy, colonic pull-through (PT) has emerged to allow cleanliness without a life-long stoma. We sought to understand outcomes of PT in a large multi-center CE population., Methods: We performed a retrospective study involving eleven pediatric hospitals. We gathered data on demographics, outcomes, and anatomical factors including colon length. Continuous variables were analyzed with Wilcoxon rank-sum tests and categorial variables with Fisher's exact tests., Results: There were 98 patients, of which the majority (n = 70, 71.4 %) never underwent PT. There were no differences in exstrophy type, demographics, or associated anomalies. Median age at PT was 1.3 years (IQR 0.3-3.7). Of the cohort that continue to use their PT, the majority (n = 16, 69.6 %) are not clean. In total, 7.1 % (n = 7) of the cohort is clean with a PT, and only one patient is continent. Clean patients have a longer colon length than those who are not clean or opt for re-do ostomy (64.0 cm [IQR 46.0-82.0] vs 26.5 cm [IQR 11.6-41.2], p = 0.005)., Conclusion: Overall, we demonstrate that most children born with CE will keep their stoma. Only a small percentage who elect to undergo colonic PT are clean for stool. Greater colon length correlates with success. This suggests that multiple factors, including colon length, are important when considering PT in a child with CE., Level of Evidence: III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Supported by laboratory and clinical investigations of adult cardiopulmonary arrest, resuscitation guidelines recommend monitoring end-tidal carbon dioxide (ETCO 2 ) as an indicator of cardiopulmonary resuscitation (CPR) quality, but they note that "specific values to guide therapy have not been established in children.", Methods: This prospective observational cohort study was a National Heart, Lung, and Blood Institute-funded ancillary study of children in the ICU-RESUS trial (Intensive Care Unit-Resuscitation Project; NCT02837497). Hospitalized children (≤18 years of age and ≥37 weeks postgestational age) who received chest compressions of any duration for cardiopulmonary arrest, had an endotracheal or tracheostomy tube at the start of CPR, and evaluable intra-arrest ETCO 2 data were included. The primary exposure was event-level average ETCO 2 during the first 10 minutes of CPR (dichotomized as ≥20 mm Hg versus <20 mm Hg on the basis of adult literature). The primary outcome was survival to hospital discharge. Secondary outcomes were sustained return of spontaneous circulation, survival to discharge with favorable neurological outcome, and new morbidity among survivors. Poisson regression measured associations between ETCO 2 and outcomes as well as the association between ETCO 2 and other CPR characteristics: (1) invasively measured systolic and diastolic blood pressures, and (2) CPR quality and chest compression mechanics metrics (ie, time to CPR start; chest compression rate, depth, and fraction; ventilation rate)., Results: Among 234 included patients, 133 (57%) had an event-level average ETCO 2 ≥20 mm Hg. After controlling for a priori covariates, average ETCO 2 ≥20 mm Hg was associated with a higher incidence of survival to hospital discharge (86/133 [65%] versus 48/101 [48%]; adjusted relative risk, 1.33 [95% CI, 1.04-1.69]; P =0.023) and return of spontaneous circulation (95/133 [71%] versus 59/101 [58%]; adjusted relative risk, 1.22 [95% CI, 1.00-1.49]; P =0.046) compared with lower values. ETCO 2 ≥20 mm Hg was not associated with survival with favorable neurological outcome or new morbidity among survivors. Average 2 ≥20 mm Hg was associated with higher systolic and diastolic blood pressures during CPR, lower CPR ventilation rates, and briefer pre-CPR arrest durations compared with lower values. Chest compression rate, depth, and fraction did not differ between ETCO 2 groups., Conclusions: In this multicenter study of children with in-hospital cardiopulmonary arrest, ETCO 2 ≥20 mm Hg was associated with better outcomes and higher intra-arrest blood pressures, but not with chest compression quality metrics., Competing Interests: Disclosures None.

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: Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs)., Design: This is an analysis of of a seven-center prospective cohort study., Setting: Seven PICUs within academic children's hospitals in the United States., Patients: Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours., Interventions: We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement., Measurements and Main Results: Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001)., Conclusions: Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology., Competing Interests: This work was supported by the following cooperative agreements from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): (UG1HD083171 to Dr. Pollack), (UG1HD049983 to Dr. Carcillo) (UG01HD049934 to Drs. Reeder, Locandro, and DeRisi), (UG1HD083170 to Dr. Hall), (UG1HD050096 to Dr. Meert), (UG1HD63108 to Dr. Zuppa), (UG1HD083166 to Dr. McQuillen), (UG1HD049981 to Dr. McQuillen); the National Heart Lung Blood Institute (1R01HL124103 to Dr. Pollack) and (K23HL138461-01A1 and 5R01HL155418-03 to Dr. Langelier), and National Institutes of Health (NIH). Dr. Maddux’s institution received funding from the National Institute for Child Health and Human Development (NICHD) (K23HD096018) and the Francis Family Foundation. Dr. Caldera disclosed work for hire and she disclosed that she is a staff research associate employed through University of California San Francisco. Dr. Hall received funding from Abbvie, Kiadis, and the American Board of Pediatrics. Drs. Zuppa, Carcillo, and McQuillen’s institutions received funding from the NICHD. Dr. Carcillo’s institution received funding from the National Institute of General Medical Sciences. Dr. DeRisi received funding from Public Health Company and Allen & Co; he disclosed that he is a scientific founder and advisor for Delve Bio; he received support for article research from Chan Zuckerberg Biohub. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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.)

Background: Illness severity scores predict mortality following pediatric critical illness. Given declining PICU mortality, we assessed the ability of the Pediatric Risk of Mortality-III (PRISM) and Pediatric Logistic Organ Dysfunction-2 (PELOD) scores to predict morbidity outcomes., Methods: Among 359 survivors <18 years in the Life After Pediatric Sepsis Evaluation multicenter prospective cohort study, we assessed functional morbidity at hospital discharge (Functional Status Scale increase ≥3 points from baseline) and health-related quality of life (HRQL; Pediatric Quality of Life Inventory or Functional Status II-R) deterioration >25% from baseline at 1, 3, 6, and 12 months post-admission. We determined discrimination of admission PRISM and admission, maximum, and cumulative 28-day PELOD with functional and HRQL morbidity at each timepoint., Results: Cumulative PELOD provided the best discrimination of discharge functional morbidity (area under the receive operating characteristics curve [AUROC] 0.81, 95% CI 0.76-0.87) and 3-month HRQL deterioration (AUROC 0.71, 95% CI 0.61-0.81). Prediction was inferior for admission PRISM and PELOD and for 6- and 12-month HRQL assessments., Conclusions: Illness severity scores have a good prediction of early functional morbidity but a more limited ability to predict longer-term HRQL. Identification of factors beyond illness severity that contribute to HRQL outcomes may offer opportunities for intervention to improve outcomes., Impact: Illness severity scores are commonly used for mortality prediction and risk stratification in pediatric critical care research, quality improvement, and resource allocation algorithms. Prediction of morbidity rather than mortality may be beneficial given declining pediatric intensive care unit mortality. The PRISM and PELOD scores have moderate to good ability to predict new functional morbidity at hospital discharge following pediatric septic shock but limited ability to predict health-related quality of life outcomes in the year following PICU admission. Further research is needed to identify additional factors beyond illness severity that may impact post-discharge health-related quality of life., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: To investigate whether change in functional status from pre-hospitalization baseline to hospital discharge is associated with long-term health-related quality of life (HRQL) among children surviving septic shock., Design: Secondary analysis of Life After Pediatric Sepsis Evaluation (LAPSE), a prospective cohort study of children with community-acquired septic shock, enrolled from January 2014 to June 2017., Setting: Twelve U.S. academic PICUs., Patients: Children, 1 month to 18 years, who survived to hospital discharge and had follow-up data for HRQL at 3 and/or 12 months., Interventions: None., Measurements and Main Results: Functional Status Scale (FSS) was assessed around enrollment to ascertain baseline status (pre-hospitalization) and at 28 days or hospital discharge. Two measures of HRQL were utilized: children with significant development delay were measured with the Functional Status II-R (FSII-R); typically, developing children were measured with the Pediatric Quality of Life Inventory (PedsQL). Each group was analyzed separately with multivariable regression modeling to determine the association between change in FSS from baseline to day 28 and HRQL at 3 and 12 months from PICU admission. Of the original 389 LAPSE participants, 224 (58%) are included. Among children with developmental delay ( n = 88), worsened FSS was associated with lower FSII-R at 3 months from PICU admission (-2.02; 95% CI, -3.34 to -0.0.71; p = 0.003), but not 12 months. Among developmentally typical children ( n = 136), worsened FSS was associated with lower PedsQL at both 3 and 12 months. Developmentally typical children with a neurologic insult during the PICU stay had the largest decrement in PedsQL at 12 months (-14.04 mo; 95% CI, -22.15 to -5.94 mo; p < 0.001). However, worsened FSS remained associated with poor HRQL-PedsQL at 3 and 12 months, after controlling for neurologic events (both p < 0.001)., Conclusions: Change in FSS during hospitalization for septic shock is associated with long-term reductions in HRQL and could serve as a useful tool for identifying children at risk for this sequela., Competing Interests: Dr. Reeder’s institution received funding from the National Institutes of Health (NIH). Drs. Reeder, Banks, Zimmerman, and Meert received support for article research from the NIH. Drs. Banks’s and Zimmerman’s institutions received funding from the National Institute of Child Health and Human Development. Dr. Banks disclosed government work. Dr. Zimmerman’s institution received funding from Immune Express; he received funding from Elsevier Publishing. 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.)

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: Develop a novel, physiology-based measurement of duty cycle (Arterial Blood Pressure-Area Duty Cycle [ABP-ADC]) and evaluate the association of ABP-ADC with intra-arrest hemodynamics and patient outcomes., Methods: This was a secondary retrospective study of prospectively collected data from the ICU-RESUS trial (NCT02837497). Invasive arterial waveform data were used to derive ABP-ADC. The primary exposure was ABP-ADC group (<30%; 30-35%; >35%). The primary outcome was systolic blood pressure (sBP). Secondary outcomes included intra-arrest physiologic goals, CPR quality targets, and patient outcomes. In an exploratory analysis, adjusted splines and receiver operating characteristic (ROC) curves were used to determine an optimal ABP-ADC associated with improved hemodynamics and outcomes using a multivariable model., Results: Of 1129 CPR events, 273 had evaluable arterial waveform data. Mean age is 2.9 years + 4.9 months. Mean ABP-ADC was 32.5% + 5.0%. In univariable analysis, higher ABP-ADC was associated with lower sBP (p < 0.01) and failing to achieve sBP targets (p < 0.01). Other intra-arrest physiologic parameters, quality metrics, and patient outcomes were similar across ABP-ADC groups. Using spline/ROC analysis and clinical judgement, the optimal ABP-ADC cut point was set at 33%. On multivariable analysis, sBP was significantly higher (point estimate 13.18 mmHg, CI95 5.30-21.07, p < 0.01) among patients with ABP-ADC < 33%. Other intra-arrest physiologic and patient outcomes were similar., Conclusions: In this multicenter cohort, a lower ABP-ADC was associated with higher sBPs during CPR. Although ABP-ADC was not associated with outcomes, further studies are needed to define the interactions between CPR mechanics and intra arrest patient physiology., 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.)

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.)

Objectives: To evaluate the association between fluid balance (FB) and health-related quality of life (HRQL) among children at 1 month following community-acquired septic shock., Design: Nonprespecified secondary analysis of the Life After Pediatric Sepsis Evaluation. FB was defined as 100 × [(cumulative PICU fluid input - cumulative PICU fluid output)/PICU admission weight]. Three subgroups were identified: low FB (< 5%), medium FB (5%-15%), and high FB (> 15%) based on cumulative FB on days 0-3 of ICU stay. HRQL was measured at ICU admission and 1 month after using Pediatric Quality of Life Inventory 4.0 Generic Core or Infant Scales or the Stein-Jessop Functional Status Scale. The primary outcome was a composite of mortality or greater than 25% decline in HRQL 1 month after admission compared with baseline., Setting: Twelve academic PICUs in the United States., Patients: Critically ill children between 1 month and 18 years, with community-acquired septic shock who survived to at least day 4., Interventions: None., Measurements and Main Results: Two hundred ninety-three patients were included of whom 66 (23%) had low FB, 127 (43%) had medium FB, and 100 (34%) had high FB. There was no difference in Pediatric Risk of Mortality Score 3 (median 11 [6, 17]), age (median 5 [1, 12]), or gender (47% female) between FB groups. After adjusting for potential confounders and comparing with medium FB, higher odds of mortality or greater than 25% HRQL decline were seen in both the low FB (odds ratio [OR] 2.79 [1.20, 6.57]) and the high FB (OR 2.16 [1.06, 4.47]), p = 0.027. Compared with medium FB, low FB (OR 4.3 [1.62, 11.84]) and high FB (OR 3.29 [1.42, 8.00]) had higher odds of greater than 25% HRQL decline., Conclusions: Over half of the children who survived septic shock had low or high FB, which was associated with a significant decline in HRQL scores. Prospective studies are needed to determine if optimization of FB can improve HRQL outcomes., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Acute disorders of consciousness (DoC) in pediatric severe sepsis are associated with increased risk of morbidity and mortality. We sought to examine the frequency of and factors associated with DoC in children with sepsis-induced organ failure., Design: Secondary analysis of the multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS)., Setting: Nine tertiary care PICUs in the United States., Patients: Children less than 18 years old admitted to a PICU with severe sepsis and at least one organ failure during a PICU stay., Interventions: None., Measurements and Main Results: The primary outcome was frequency of DoC, defined as Glasgow Coma Scale (GCS) less than 12 in the absence of sedatives during an ICU stay, among children with severe sepsis and the following: single organ failure, nonphenotypeable multiple organ failure (MOF), MOF with one of the PHENOMS phenotypes (immunoparalysis-associated MOF [IPMOF], sequential liver failure-associated MOF, thrombocytopenia-associated MOF), or MOF with multiple phenotypes. A multivariable logistic regression analysis was performed to evaluate the association between clinical variables and organ failure groups with DoC. Of 401 children studied, 71 (18%) presented with DoC. Children presenting with DoC were older (median 8 vs 5 yr; p = 0.023), had increased hospital mortality (21% vs 10%; p = 0.011), and more frequently presented with both any MOF (93% vs 71%; p < 0.001) and macrophage activation syndrome (14% vs 4%; p = 0.004). Among children with any MOF, those presenting with DoC most frequently had nonphenotypeable MOF and IPMOF (52% and 34%, respectively). In the multivariable analysis, older age (odds ratio, 1.07; 95% CI, 1.01-1.12) and any MOF (3.22 [1.19-8.70]) were associated with DoC., Conclusions: One of every five children with severe sepsis and organ failure experienced acute DoC during their PICU stay. Preliminary findings suggest the need for prospective evaluation of DoC in children with sepsis and MOF., Competing Interests: Dr. Cheung received funding from the Deans Summer Research Program (University of Pittsburgh School of Medicine). Dr. Kernan received funding from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) (K12HD047349). Drs. Berg’s, Zuppa’s, Notterman’s, Pollack’s, Wesssel’s, Meert’s, Hall’s, Newth’s, Doctor’s, Shanley’s, Cornell’s, Harrison’s, Banks’s, Reeder’s, Holubkov’s, Fink’s, and Carcillo’s institutions received funding from the National Institutes of Health (NIH). Drs. Berg, Zuppa, Pollack, Wessel, Meert, Hall, Newth, Shanley, Harrison, Banks, Reeder, Holubkov, Carcillo, and Fink received support for article research from the NIH. Drs. Zuppa’s, Banks’s, and Carcillo’s institutions received funding from the NICHD. Dr. Hall received funding from AbbVie (service as a consultant [active]) and LaJolla Pharmaceuticals (service as a consultant [completed]). He is a consultant for the American Board of Pediatrics Pediatric Critical Care Subboard. He receives licensing income from Kiadis. Dr. Fink’s institution received funding from the NIH and Neurocritical Care Society. She is a consultant for the American Board of Pediatrics Pediatric Critical Care Subboard. Dr. Doctor’s institution received funding from the Department of Defense and KaloCyte. Dr. Holubkov received funding from Pfizer and the Physicians Committee for Responsible Medicine; he serves on Data Safety Monitoring Boards for Pfizer. Dr. Carcillo’s institution received funding from the National Institute of General Medical Sciences. Dr. Lin has disclosed that he does 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.)

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: Sepsis is more common in males than females, but whether outcomes differ by sex in various pediatric age groups is unclear. The Life After Pediatric Sepsis Evaluation (LAPSE) was a multicenter prospective cohort study that evaluated health-related quality of life (HRQL) in children after community-acquired septic shock. In this secondary analysis, we evaluated whether male children are at increased risk of mortality or long-term decline in HRQL than female children by age group. Methods: Children (1 month-18 years) with community-acquired septic shock were recruited from 12 pediatric intensive care units in the U.S. Data included sex, age group (<1 year, 1-<13 years, 13-18 years), acute illness severity (acute organ dysfunction and inflammation), and longitudinal assessments of HRQL and mortality. Persistent decline in HRQL was defined as a 10% decrease in HRQL comparing baseline to 3 months following admission. Male and female children were stratified by age group and compared to evaluate the difference in the composite outcome of death or persistent decline in HRQL using the Cochran-Mantel-Haenszel test. Results: Of 389 children, 54.2% ( n  = 211) were male. Overall, 10% (21/211) of males and 12% (22/178) of females died by 3 months ( p  = 0.454). Among children with follow-up data, 41% (57/138) of males and 44% (48/108) of females died or had persistent decline in HRQL at 3 months ( p  = 0.636), with no observed difference by sex when stratified by age group. There was no significant difference in acute illness severity between males and females overall or stratified by age group. Conclusions: In this secondary analysis of the LAPSE cohort, HRQL, and mortality were not different between male and female children when stratified by age group. There were no significant differences by sex across multiple measures of illness severity or treatment intensity.

Background: Tobacco smoke exposure increases the risk and severity of lower respiratory tract infections in children, yet the mechanisms remain unclear. We hypothesized that tobacco smoke exposure would modify the lower airway microbiome., Methods: Secondary analysis of a multicenter cohort of 362 children between ages 31 days and 18 years mechanically ventilated for >72 h. Tracheal aspirates from 298 patients, collected within 24 h of intubation, were evaluated via 16 S ribosomal RNA sequencing. Smoke exposure was determined by creatinine corrected urine cotinine levels ≥30 µg/g., Results: Patients had a median age of 16 (IQR 568) months. The most common admission diagnosis was lower respiratory tract infection (53%). Seventy-four (20%) patients were smoke exposed and exhibited decreased richness and Shannon diversity. Smoke exposed children had higher relative abundances of Serratia spp., Moraxella spp., Haemophilus spp., and Staphylococcus aureus. Differences were most notable in patients with bacterial and viral respiratory infections. There were no differences in development of acute respiratory distress syndrome, days of mechanical ventilation, ventilator free days at 28 days, length of stay, or mortality., Conclusion: Among critically ill children requiring prolonged mechanical ventilation, tobacco smoke exposure is associated with decreased richness and Shannon diversity and change in microbial communities., Impact: Tobacco smoke exposure is associated with changes in the lower airways microbiome but is not associated with clinical outcomes among critically ill pediatric patients requiring prolonged mechanical ventilation. This study is among the first to evaluate the impact of tobacco smoke exposure on the lower airway microbiome in children. This research helps elucidate the relationship between tobacco smoke exposure and the lower airway microbiome and may provide a possible mechanism by which tobacco smoke exposure increases the risk for poor outcomes in children., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: The incidence and optimal management of rectal prolapse following repair of an anorectal malformation (ARM) has not been well-defined., Methods: A retrospective cohort study was performed utilizing data from the Pediatric Colorectal and Pelvic Learning Consortium registry. All children with a history of ARM repair were included. Our primary outcome was rectal prolapse. Secondary outcomes included operative management of prolapse and anoplasty stricture following operative management of prolapse. Univariate analyses were performed to identify patient factors associated with our primary and secondary outcomes. A multivariable logistic regression was developed to assess the association between laparoscopic ARM repair and rectal prolapse., Results: A total of 1140 patients met inclusion criteria; 163 (14.3%) developed rectal prolapse. On univariate analysis, prolapse was significantly associated with male sex, sacral abnormalities, ARM type, ARM complexity, and laparoscopic ARM repairs (p < 0.001). ARM types with the highest rates of prolapse included rectourethral-prostatic fistula (29.2%), rectovesical/bladder neck fistula (28.8%), and cloaca (25.0%). Of those who developed prolapse, 110 (67.5%) underwent operative management. Anoplasty strictures developed in 27 (24.5%) patients after prolapse repair. After controlling for ARM type and hospital, laparoscopic ARM repair was not significantly associated with prolapse (adjusted odds ratio (95% CI): 1.50 (0.84, 2.66), p = 0.17)., Conclusion: Rectal prolapse develops in a significant subset of patients following ARM repair. Risk factors for prolapse include male sex, complex ARM type, and sacral abnormalities. Further research investigating the indications for operative management of prolapse and operative techniques for prolapse repair are needed to define optimal treatment., Type of Study: Retrospective cohort study., Level of Evidence: II., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background/rationale: Anorectal malformations (ARM) are associated with congenital anomalies of the spine, but the impact of a minor spinal cord dysraphism (mSCD) on fecal continence in the setting of ARM remains unclear., Materials/methods: A retrospective review was performed utilizing data from the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) registry. The patient cohort was reviewed for ARM type, mSCD screening/incidence/neurosurgical intervention and age-based BMP utilization., Results: 987 patients with ARM were categorized into mild (38%), moderate (32%) or complex (19%). 694 (70%) had normal spinal (NS) status. 271 (27.5%) patients had mSCD. MRI alone (49%) was the most common screening test for mSCD. US screening had a positive predictive value of 86.3% and a negative predictive value of 67.1%. Surgical intervention rates for mSCD ranged between 13% and 77% at a median age of 0.6-5.2 years. 726 (73.6%) patients were prescribed BMP (74.4% NS, 77.5% mSCD). Laxatives were most utilized BMP in all groups <5yo. ≥5yo, enema utilization increased with ARM complexity independent of spine status (with or without neurosurgical intervention). Neurosurgical intervention did not affect BMP utilization at any age or with any ARM when mSCD was identified., Conclusions: MSCD influence on bowel function in the setting ARM remains unclear. No significant impact of mSCD was noted on ARM patient bowel management program utilization. Variability exists within PCPLC site with screening and intervention for mSCD in patients with ARM. Future studies with standardized care may be needed to elucidate the true impact of mSCD on long term patient outcomes in ARM patients., Type of Study: Retrospective Comparative Study., Level of Evidence: III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To describe epinephrine dosing distribution using time-stamped data and assess the impact of dosing strategy on survival after ECPR in children., Methods: This was a retrospective study at five pediatric hospitals of children <18 years with an in-hospital ECPR event. Mean number of epinephrine doses was calculated for each 10-minute CPR interval and compared between survivors and non-survivors. Patients were also divided by dosing strategy into a frequent epinephrine group (dosing interval of ≤5 min/dose throughout the first 30 minutes of the event), and a limited epinephrine group (dosing interval of ≤5 min/dose for the first 10 minutes then >5 min/dose for the time between 10 and 30 minutes)., Results: A total of 191 patients were included. Epinephrine was not evenly distributed throughout ECPR, with 66% of doses being given during the first half of the event. Mean number of epinephrine doses was similar between survivors and non-survivors the first 10 minutes (2.7 doses). After 10 minutes, survivors received fewer doses than non-survivors during each subsequent 10-minute interval. Adjusted survival was not different between strategy groups [OR of survival for frequent epinephrine strategy: 0.78 (95% CI 0.36-1.69), p = 0.53]., Conclusions: Survivors received fewer doses than non-survivors after the first 10 minutes of CPR and although there was no statistical difference in survival based on dosing strategy, the findings of this study question the conventional approach to EPCR analysis that assumes dosing is evenly distributed., 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.)

Aims: To characterize respiratory failure prior to pediatric in-hospital cardiac arrest (IHCA) and to associate pre-arrest respiratory failure characteristics with survival outcomes., Methods: This is a single-center, retrospective cohort study from a prospectively identified cohort of children <18 years in intensive care units (ICUs) who received cardiopulmonary resuscitation (CPR) for ≥1 minute between January 1, 2017 and June 30, 2021, and were receiving invasive mechanical ventilation (IMV) in the hour prior to IHCA. Patient characteristics, ventilatory support and gas exchange immediately pre-arrest were described and their association with the return of spontaneous circulation (ROSC) was measured., Results: In the 187 events among 154 individual patients, the median age was 0.9 [0.2, 2.4] years, and CPR duration was 7.5 [3, 29] minutes. Respiratory failure was acute prior to 106/187 (56.7%) events, and the primary indication for IMV was respiratory in nature in 107/187 (57.2%) events. Immediately pre-arrest, the median positive end-expiratory pressure was 8 [5, 10] cmH 2 O; mean airway pressure was 13 [10,18] cmH 2 O; peak inspiratory pressure was 28 [24, 35] cmH 2 O; and fraction of inhaled oxygen (FiO2) was 0.40 [0.25, 0.80]. Pre-arrest FiO2 was lower in patients with ROSC vs. without ROSC (0.30 vs. 0.99; p < 0.001). Patients without ROSC had greater severity of pre-arrest oxygenation failure (p < 0.001) as defined by oxygenation index, oxygen saturation index, P/F ratio or S/F ratio., Conclusions: There was substantial heterogeneity in respiratory failure characteristics and ventilatory requirements pre-arrest. Higher pre-arrest oxygen requirement and greater degree of oxygenation failure were associated with worse survival 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.)

Background: In refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) is a rescue therapy to prevent ventilator-induced lung injury. Optimal ventilator parameters during ECMO remain unknown. Our objective was to describe the association between mortality and ventilator parameters during ECMO for neonatal and pediatric respiratory failure., Methods: We performed a secondary analysis of the Bleeding and Thrombosis on ECMO dataset. Ventilator parameters included breathing frequency, tidal volume, peak inspiratory pressure, PEEP, dynamic driving pressure, pressure support, mean airway pressure, and F IO 2 . Parameters were evaluated before cannulation, on the calendar day of ECMO initiation (ECMO day 1), and the day before ECMO separation., Results: Of 237 included subjects analyzed, 64% were neonates, of whom 36% had a congenital diaphragmatic hernia. Of all the subjects, 67% were supported on venoarterial ECMO. Overall in-hospital mortality was 35% ( n = 83). The median (interquartile range) PEEP on ECMO day 1 was 8 (5.0-10.0) cm H 2 O for neonates and 10 (8.0-10.0) cm H 2 O for pediatric subjects. By multivariable analysis, higher PEEP on ECMO day 1 in neonates was associated with lower odds of in-hospital mortality (odds ratio 0.77, 95% CI 0.62-0.92; P = .01), with a further amplified effect in neonates with congenital diaphragmatic hernia (odds ratio 0.59, 95% CI 0.41-0.86; P = .005). No ventilator type or parameter was associated with mortality in pediatric subjects., Conclusions: Avoiding low PEEP on ECMO day 1 for neonates on ECMO may be beneficial, particularly those with a congenital diaphragmatic hernia. No additional ventilator parameters were associated with mortality in either neonatal or pediatric subjects. PEEP is a modifiable parameter that may improve neonatal survival during ECMO and requires further investigation., Competing Interests: Dr Dalton is a consultant to industry of Entegrion, Hemocue, is the medical director of Innovative ECMO Concepts, and is on the advisory board for BREATHE-Oxi 1 (Abiomed), Medtronic. The other authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Objective: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT., Methods: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF)., Results: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort., Conclusions: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion., (© 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.)

Purpose: Fecal incontinence is a problem for many patients born with an anorectal malformation (ARM) that can impact quality of life. It is unknown if racial, ethnic, and socioeconomic disparities relate to fecal continence in these children. We sought to examine outcomes and potential disparities in care., Methods: We performed a multicenter retrospective study of children > 3y with ARM evaluated at sites participating in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC). The primary outcome was fecal continence. We evaluated for associations between fecal continence and race, sex, age, and insurance status., Results: 509 patients with ARM from 11 institutions were included. Overall, 24% reported complete fecal continence, and fecal continence was associated with older age (p < .001). For school-aged children, 27% reported complete continence, while 53% reported none. On univariate analysis, patients with combined private and public insurance showed lower rates of continence when compared to those with private insurance (23 vs. 12%; p = 0.02). Age was associated with continence on univariate and multivariable analyses., Conclusion: Rates of complete fecal continence in this population are low. Differences based on payor status may exist. There were no observed disparities related to sex and race. Further investigation is warranted to improve care for this patient population., Level of Evidence: III., Type of Study: Multi-institutional retrospective comparative study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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).)

Background: VACTERL association is defined by the presence of 3 or more anomalies in any of the following systems: vertebral, anorectal, cardiac, trachea-esophageal, renal, or limb. This study hypothesized that the presence of VACTERL association would correlate with an increased risk of gynecologic anomalies in patients with anorectal malformation (ARM)., Methods: This study is a cross-sectional, retrospective analysis from the prospectively collected, multicenter registry of the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC). The 834 female patients with ARM who were enrolled in the registry by January 1, 2020 were included in this study. The relationship of VACTERL association with presence of a gynecologic anomaly was evaluated with Fisher's exact test. The relationship of each VACTERL system with presence of a gynecologic anomaly was assessed in patients with cloaca, rectovestibular fistulas and rectoperineal fistulas. P-values reported were based on a 2-sided alternative and considered significant when less than 0.05., Results: 834 patients with ARM underwent VACTERL screening and gynecologic evaluation with the three most common subtypes being cloaca (n = 215, 25.8%), rectovestibular fistula (n = 191, 22.9%) and rectoperineal fistula (n = 194, 23.3%). A total of 223 (26.7%) patients with ARM had gynecologic anomalies. VACTERL association was seen in 380 (45.6%) of patients with ARM. Gynecologic anomalies were present in 149 (39.1%) vs. 74 (16.3%) of subjects with vs. without VACTERL association (p < 0.001). VACTERL association did not significantly increase the risk of gynecologic anomaly in patients with cloaca and VACTERL (n = 88, 61.5%) vs. cloaca without VACTERL (n = 39, 54.2% p = 0.308). VACTERL association increased the risk of gynecologic anomalies in patients with rectoperineal fistulas (n = 7, 14.9% vs n = 9, 6.1% p = 0.014) and rectovestibular fistulas (n = 19, 31.1% vs. n = 13, 10.0% p<0.001). In patients with ARM who had a VACTERL association, when one of the associated anomalies was renal, there was an even higher risk of having an associated gynecologic anomaly (n = 138, 44.2% vs. n = 85, 16.3% p<0.001)., Conclusions: VACTERL association in patients with rectoperineal and rectovestibular fistulas correlates with an increased risk of gynecologic anomalies. The presence of VACTERL associated findings, especially renal, should prompt a thorough evaluation of the gynecologic system., Level of Evidence: III. Retrospective comparative study., (Copyright © 2022. Published by Elsevier Inc.)

To determine associations between anticoagulation practices and bleeding and thrombosis during pediatric extracorporeal membrane oxygenation (ECMO), we performed a secondary analysis of prospectively collected data which included 481 children (<19 years), between January 2012 and September 2014. The primary outcome was bleeding or thrombotic events. Bleeding events included a blood product transfusion >80 ml/kg on any day, pulmonary hemorrhage, or intracranial bleeding, Thrombotic events included pulmonary emboli, intracranial clot, limb ischemia, cardiac clot, and arterial cannula or entire circuit change. Bleeding occurred in 42% of patients. Five percent of subjects thrombosed, of which 89% also bled. Daily bleeding odds were independently associated with day prior activated clotting time (ACT) (OR 1.03, 95% CI= 1.00, 1.05, p =0.047) and fibrinogen levels (OR 0.90, 95% CI 0.84, 0.96, p <0.001). Thrombosis odds decreased with increased day prior heparin dose (OR 0.88, 95% CI 0.81, 0.97, p =0.006). Lower ACT values and increased fibrinogen levels may be considered to decrease the odds of bleeding. Use of this single measure, however, may not be sufficient alone to guide optimal anticoagulation practice during ECMO.

Purpose: Fecal continence is a concern for many patients with idiopathic constipation and can significantly impact quality of life. It is unknown whether racial, ethnic, and socioeconomic disparities are seen in fecal continence within the idiopathic constipation population. We aimed to evaluate fecal continence and associated demographic characteristics in children with idiopathic constipation referred for surgical evaluation., Methods: A multicenter retrospective study of children with idiopathic constipation was performed at sites participating in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC). All patients >3y of age with idiopathic constipation diagnosis were included. The primary outcome was fecal continence, categorized as complete (no accidents ever), daytime (no accidents during the day), partial (occasional incontinence day/night), and none (incontinent). We evaluated for associations between fecal continence and race, sex, age, insurance status, and other patient-level factors, employing Kruskal-Wallis and trend tests., Results: 458 patients with idiopathic constipation from 12 sites were included. The median age of diagnosis was 4.1 years. Only 25% of patients referred for surgical evaluation were completely continent. Age at the visit was significantly associated with fecal continence level (p = 0.002). In addition, patients with public and mixed public and private insurance had lower levels of continence (p<0.001). Patients with developmental delay were also more likely to have lower continence levels (p = 0.009) while diagnoses such as anxiety, ADD/ADHD, autism, depression, obsessive-compulsive disorder were not associated. Approximately 30% of patients had an ACE operation (antegrade continence enema) at a median age of 9.2 years at operation. Black patients were significantly less likely to undergo ACE operation (p = 0.016) when compared to white patients., Conclusion: We observed data that suggest differences in fecal incontinence rates based on payor status. Further investigation is needed to characterize these potential areas of disparate care., Level of Evidence: Level III., (Published by Elsevier Inc.)

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.)

Background: Medical management, primarily a fat-modified diet (FMD), is the mainstay of treatment for most patients with chylothorax. Duration of FMD is traditionally reported as 6 weeks, but no studies have demonstrated the shortest effective duration that prevents recurrence of chylothorax. The aim of this study was to decrease FMD duration to 2 weeks in children with postoperative chylothorax without a significant increase in recurrence., Methods: This single-center study included pediatric (aged <18 years) patients in whom chylothorax developed within 30 days of cardiac surgery. Patients with cavopulmonary anastomoses were excluded. The preintervention cohort consisted of 19 patients with a diagnosis of chylothorax between February 2014 and June 2015, and the postintervention cohort comprised 98 patients from July 2015 to December 2019. FMD duration was decreased from 6 weeks to 4 weeks in May 2016 and to 2 weeks in June 2018. Recurrence was defined as a return of a chylous effusion requiring chest tube placement or hospital readmission within 30 days of resuming a regular diet., Results: The median duration of FMD decreased from 42 days (interquartile range, 30, 43 days) in the preintervention cohort to 26 days (interquartile range, 14, 29 days) in the postintervention cohort, with no recurrence of chylothorax in any group. Compliance with the FMD duration instruction in the 6-week, 4-week, and 2-week groups was 100%, 84%, and 67% respectively. Compared with the first 6 months, compliance with the 2-week FMD instruction during the final 12 months increased from 40% (6/15) to 79% (26/33)., Conclusions: At the study center, FMD duration decreased from 6 weeks to 2 weeks without any recurrence of chylothorax., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks., Data Sources: A prospective, observational cohort study., Study Selection: Children with sepsis and organ failure in nine pediatric intensive care units in the United States., Data Extraction: Two hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin., Data Synthesis: Group 1 had normal CRP and ferritin levels ( n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout ( n = 80; 5% mortality); Group 3 had high ferritin levels alone ( n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels ( n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels ( n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines., Conclusions: Bedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies., Competing Interests: Drs. Horvat’s, Banks’, Newth’s, Shanley’s, Zuppa’s, Sward’s, Dean’s, and Carcillo’s and institutions received funding from the National Institutes of Child Health and Human Development (NICHD). Drs. Banks’s, Berg’s, Wessel’s, Pollack’s, Meert’s, Hall’s, Newth’s, Doctor’s, Shanley’s, Cornell’s, Harrison’s, Zuppa’s, Reeder’s, Holubkov’s, Dean’s, and Carcillo’s institutions received funding from the National Institutes of Health (NIH). Drs. Horvat, Banks, Park, Kernan, Canna, Berg, Wessel, Pollack, Meert, Hall, Newth, Doctor, Shanley, Harrison, Zuppa, Reeder, Sward, Holubkov, Dean, and Carcillo received support for article research from the NIH. Drs. Horvat and Carcillo disclosed the off-label product use of Tumor Necrosis Factor Receptor Apoptosis Inducing Ligand Interleukin Receptor Antagonist Protein. Dr. Kernan’s institution received funding from the NICHD (K12HD047349). Dr. Canna’s institution received funding from InnVention Therapeutix; he received funding from Simcha Therapeutics. Dr. Pollack disclosed that his research is supported by philanthropy from Mallinckrodt Pharmaceuticals. Dr. Hall received funding from La Jolla Pharmaceuticals, Abbvie, and Kiadis. Dr. Hall received funding from Bristol Myers-Squibb (for service on an advisory board) and LaJolla Pharmaceuticals (service as a consultant), both unrelated to the current submission. Dr. Newth received funding from Philips Research North America, Hamilton Medical AG, and Nihon Kohden Orange Med. Dr. Doctor’s institution received funding from the Department of Defense and KaloCyte. Dr. Shanley received funding from Springer publishing, International Pediatric Research Foundation, and Pediatric Academic Societies. Dr. Cornell disclosed he is co-founder of Pre-Dixon Bio. Dr. Holubkov’s institution received funding from AltaThera Pharmaceuticals; he received funding from Pfizer (Data Safety Monitoring Board [DSMB] member), Medimmune (DSMB member), the Physicians Committee for Responsible Medicine (biostatistical consulting), DURECT corporation (biostatistical consulting), Armaron Bio (DSMB past member), and St Jude Medical (DSMB past member). Dr. Carcillo’s institution received funding from the National Institutes of General Medical Sciences. 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: 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.)