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Objective: Quantify hypotension burden using high-resolution continuous arterial blood pressure (ABP) data and determine its association with outcome after pediatric cardiac arrest., Design: Retrospective observational study., Setting: Academic PICU., Patients: Children 18 years old or younger admitted with in-of-hospital or out-of-hospital cardiac arrest who had invasive ABP monitoring during postcardiac arrest care., Interventions: None., Measurements and Main Results: High-resolution continuous ABP was analyzed up to 24 hours after the return of circulation (ROC). Hypotension burden was the time-normalized integral area between mean arterial pressure (MAP) and fifth percentile MAP for age. The primary outcome was unfavorable neurologic status (pediatric cerebral performance category ≥ 3 with change from baseline) at hospital discharge. Mann-Whitney U tests compared hypotension burden, duration, and magnitude between favorable and unfavorable patients. Multivariable logistic regression determined the association of unfavorable outcomes with hypotension burden, duration, and magnitude at various percentile thresholds from the 5th through 50th percentile for age. Of 140 patients (median age 53 [interquartile range 11-146] mo, 61% male); 63% had unfavorable outcomes. Monitoring duration was 21 (7-24) hours. Using a MAP threshold at the fifth percentile for age, the median hypotension burden was 0.01 (0-0.11) mm Hg-hours per hour, greater for patients with unfavorable compared with favorable outcomes (0 [0-0.02] vs. 0.02 [0-0.27] mm Hg-hr per hour, p < 0.001). Hypotension duration and magnitude were greater for unfavorable compared with favorable patients (0.03 [0-0.77] vs. 0.71 [0-5.01]%, p = 0.003; and 0.16 [0-1.99] vs. 2 [0-4.02] mm Hg, p = 0.001). On logistic regression, a 1-point increase in hypotension burden below the fifth percentile for age (equivalent to 1 mm Hg-hr of burden per hour of recording) was associated with increased odds of unfavorable outcome (adjusted odds ratio [aOR] 14.8; 95% CI, 1.1-200; p = 0.040). At MAP thresholds of 10th-50th percentiles for age, MAP burden below the threshold was greater in unfavorable compared with favorable patients in a dose-dependent manner., Conclusions: High-resolution continuous ABP data can be used to quantify hypotension burden after pediatric cardiac arrest. The burden, duration, and magnitude of hypotension are associated with unfavorable neurologic outcomes., Competing Interests: Dr. Nadkarni is the president of the Society of Critical Care Medicine (SCCM) 2023. This work is not intended to reflect the views of SCCM. Dr. Morgan receives research support from the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) (K23HL148541). Dr. Kirschen receives research support from the NIH to his institution (National Institute of Neurological Disorders and Stroke K23NS116120), Children’s Hospital of Philadelphia Resuscitation Science Center. Mr. Burnett disclosed work for hire. Dr. Sutton’s institution received funding from the NHLBI. 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.)

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).)

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.)

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

Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF's protective mechanisms and optimize its therapeutic application in post-arrest care., (© 2024. The Author(s).)

Objective: We aimed to investigate the association of recent team leader simulation training (<6 months) and years of clinical experience (≥4 years) with chest compression quality during in-hospital cardiac arrest (IHCA)., Methods: This cohort study of IHCA in four Danish hospitals included cases with data on chest compression quality and team leader characteristics. We assessed the impact of recent simulation training and experienced team leaders on longest chest compression pause duration (primary outcome), chest compression fraction (CCF), and chest compression rates within guideline recommendations using mixed effects models., Results: Of 157 included resuscitation attempts, 45% had a team leader who recently participated in simulation training and 66% had an experienced team leader. The median team leader experience was 7 years [Q1; Q3: 4; 11]. The median duration of the longest chest compression pause was 16 s [10; 30]. Having a team leader with recent simulation training was associated with significantly shorter longest pause durations (difference: -7.11 s (95%-CI: -12.0; -2.2), p = 0.004), a higher CCF (difference: 3% (95%-CI: 2.0; 4.0%), p < 0.001) and with less guideline compliant chest compression rates (odds ratio: 0.4 (95%-CI: 0.19; 0.84), p = 0.02). Having an experienced team leader was not associated with longest pause duration (difference: -1.57 s (95%-CI: -5.34; 2.21), p = 0.42), CCF (difference: 0.7% (95%-CI: -0.3; 1.7), p = 0.17) or chest compression rates within guideline recommendations (odds ratio: 1.55 (95%-CI: 0.91; 2.66), p = 0.11)., Conclusion: Recent simulation training of team leaders, but not years of team leader experience, was associated with shorter chest compression pauses during IHCA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JW serves as the Chair of the Young European Resuscitation Council (ERC). VMN is an executive committee member of ILCOR. He serves on the executive committee of the Society of Critical Care Medicine (SCCM), but the views expressed in this manuscript are his, and are not intended to represent the opinion of the SCCM. VMN & RAB serves as editorial board members of Resuscitation. KGL is a member of the ILCOR Education, Implementation and Teams Task Force, serves as the Young ERC Resuscitation Plus Editor, and is an ERC Advanced Life Support Science and Education Committee member. BL, RPN, RH, KK, HK, and RAB declared no competing interest for this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. 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: The association between chest compression (CC) pause duration and pediatric in-hospital cardiac arrest survival outcomes is unknown. The American Heart Association has recommended minimizing pauses in CC in children to <10 seconds, without supportive evidence. We hypothesized that longer maximum CC pause durations are associated with worse survival and neurological outcomes., Methods: In this cohort study of index pediatric in-hospital cardiac arrests reported in pediRES-Q (Quality of Pediatric Resuscitation in a Multicenter Collaborative) from July of 2015 through December of 2021, we analyzed the association in 5-second increments of the longest CC pause duration for each event with survival and favorable neurological outcome (Pediatric Cerebral Performance Category ≤3 or no change from baseline). Secondary exposures included having any pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds per 2 minutes., Results: We identified 562 index in-hospital cardiac arrests (median [Q1, Q3] age 2.9 years [0.6, 10.0], 43% female, 13% shockable rhythm). Median length of the longest CC pause for each event was 29.8 seconds (11.5, 63.1). After adjustment for confounders, each 5-second increment in the longest CC pause duration was associated with a 3% lower relative risk of survival with favorable neurological outcome (adjusted risk ratio, 0.97 [95% CI, 0.95-0.99]; P =0.02). Longest CC pause duration was also associated with survival to hospital discharge (adjusted risk ratio, 0.98 [95% CI, 0.96-0.99]; P =0.01) and return of spontaneous circulation (adjusted risk ratio, 0.93 [95% CI, 0.91-0.94]; P <0.001). Secondary outcomes of any pause >10 seconds or >20 seconds and number of CC pauses >10 seconds and >20 seconds were each significantly associated with adjusted risk ratio of return of spontaneous circulation, but not survival or neurological outcomes., Conclusions: Each 5-second increment in longest CC pause duration during pediatric in-hospital cardiac arrest was associated with lower chance of survival with favorable neurological outcome, survival to hospital discharge, and return of spontaneous circulation. Any CC pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds were significantly associated with lower adjusted probability of return of spontaneous circulation, but not survival or neurological outcomes., Competing Interests: Disclosures Dr Lauridsen received funding from the AP Møller Foundation and EliteForsk from the Danish Ministry for Higher Education and Research. Dr Nadkarni received unrestricted research funding to his institution from the National Institutes of Health, Agency for Healthcare Research and Quality, Zoll Medical, and Nihon-Kohden Inc, and volunteers on scientific advisory committees for the American Heart Association, Citizen CPR Foundation, INSPIRE simulation research network, and Citizen CPR Foundation. Dr Nadkarni is president of the Society of Critical Care Medicine (2023–2024). The views presented in this article reflect his views as an individual and are not intended to represent the opinions of the Society of Critical Care Medicine. D.E. Niles was an employee of Children’s Hospital of Philadelphia at the time of data collection and analysis and is currently an employee of Philips Medical. Dr Morgan receives funding from the National Institutes of Health career development award from the National Heart, Lung, and Blood Institute (award K23HL148541). Dr Raymond receives compensation as an adjudicator for the Pediatric Heart Network COMPASS trial from New England Research Institutes, Inc.

Background: Annually 15,200 children suffer an in-hospital cardiac arrest (IHCA) in the US. Ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) is the initial rhythm in 10-15% of these arrests. We sought to evaluate the association of number of shocks and early dose escalation with survival for initial VF/pVT in pediatric IHCA., Methods: Using 2000-2020 data from the American Heart Association's (AHA) Get with the Guidelines®-Resuscitation (GWTG-R) registry, we identified children >48 hours of life and ≤18 years who had an IHCA from initial VF/pVT and received defibrillation., Results: There were 251 subjects (37.7%) who received a single shock and 415 subjects (62.3%) who received multiple shocks. Baseline and cardiac arrest characteristics did not differ between those who received a single shock versus multiple shocks except for duration of arrest and calendar year. The median first shock dose was consistent with AHA dosing recommendations and not different between those who received a single shock versus multiple shocks. Survival was improved for those who received a single shock compared to multiple shocks. However, no difference in survival was noted between those who received 2, 3, or ≥4 shocks. Of those receiving multiple shocks, no difference was observed with early dose escalation., Conclusions: In pediatric IHCA, most patients with initial VF/pVT require more than one shock. No distinctions in patient or pre-arrest characteristics were identified between those who received a single shock versus multiple shocks. Subjects who received a single shock were more likely to survive to hospital discharge even after adjusting for duration of resuscitation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Tia Raymond reports she is a paid consultant of New England Research Institutes, Inc., as a member of the adjudication committee for the COMPASS Trial (Comparison of Methods for Pulmonary Blood Flow Augmentation in Neonates: Shunt versus Stent. Dianne Atkins reports she is a paid member of the Data Monitoring Safety Board for the Pediatric Heart Network, a multicenter study funded by NHLBI’., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.)

Aim: Cerebral blood flow (CBF) is dysregulated after cardiac arrest. It is unknown if post-arrest CBF is associated with outcome. We aimed to determine the association of CBF derived from arterial spin labelling (ASL) MRI with outcome after pediatric cardiac arrest., Methods: Retrospective observational study of patients ≤18 years who had a clinically obtained brain MRI within 7 days of cardiac arrest between June 2005 and December 2019. Primary outcome was unfavorable neurologic status: change in Pediatric Cerebral Performance Category (PCPC) ≥1 from pre-arrest that resulted in hospital discharge PCPC 3-6. We measured CBF in whole brain and regions of interest (ROIs) including frontal, parietal, and temporal cortex, caudate, putamen, thalamus, and brainstem using pulsed ASL. We compared CBF between outcome groups using Wilcoxon Rank-Sum and performed logistic regression to associate each region's CBF with outcome, accounting for age, sex, and time between arrest and MRI., Results: Forty-eight patients were analyzed (median age 2.8 [IQR 0.95, 8.8] years, 65% male). Sixty-nine percent had unfavorable outcome. Time from arrest to MRI was 4 [3,5] days and similar between outcome groups (p = 0.39). Whole brain median CBF was greater for unfavorable compared to favorable groups (28.3 [20.9,33.0] vs. 19.6 [15.3,23.1] ml/100 g/min, p = 0.007), as was CBF in individual ROIs. Greater CBF in the whole brain and individual ROIs was associated with higher odds of unfavorable outcome after controlling for age, sex, and days from arrest to MRI (aOR for whole brain 19.08 [95% CI 1.94, 187.41])., Conclusion: CBF measured 3-5 days after pediatric cardiac arrest by ASL MRI was independently associated with unfavorable outcome., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Kirschen received NIH support to his institution. The remaining authors have no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To quantify time dependent probabilities of outcomes in patients after in-hospital cardiac arrest as a function of duration of cardiopulmonary resuscitation, defined as the interval between start of chest compression and the first return of spontaneous circulation or termination of resuscitation., Design: Retrospective cohort study., Setting: Multicenter prospective in-hospital cardiac arrest registry in the United States., Participants: 348 996 adult patients (≥18 years) with an index in-hospital cardiac arrest who received cardiopulmonary resuscitation from 2000 through 2021., Main Outcome Measures: Survival to hospital discharge and favorable functional outcome at hospital discharge, defined as a cerebral performance category score of 1 (good cerebral performance) or 2 (moderate cerebral disability). Time dependent probabilities of subsequently surviving to hospital discharge or having favorable functional outcome if patients pending the first return of spontaneous circulation at each minute received further cardiopulmonary resuscitation beyond the time point were estimated, assuming that all decisions on termination of resuscitation were accurate (that is, all patients with termination of resuscitation would have invariably failed to survive if cardiopulmonary resuscitation had continued for a longer period of time)., Results: Among 348 996 included patients, 233 551 (66.9%) achieved return of spontaneous circulation with a median interval of 7 (interquartile range 3-13) minutes between start of chest compressions and first return of spontaneous circulation, whereas 115 445 (33.1%) patients did not achieve return of spontaneous circulation with a median interval of 20 (14-30) minutes between start of chest compressions and termination of resuscitation. 78 799 (22.6%) patients survived to hospital discharge. The time dependent probabilities of survival and favorable functional outcome among patients pending return of spontaneous circulation at one minute's duration of cardiopulmonary resuscitation were 22.0% (75 645/343 866) and 15.1% (49 769/328 771), respectively. The probabilities decreased over time and were <1% for survival at 39 minutes and <1% for favorable functional outcome at 32 minutes' duration of cardiopulmonary resuscitation., Conclusions: This analysis of a large multicenter registry of in-hospital cardiac arrest quantified the time dependent probabilities of patients' outcomes in each minute of duration of cardiopulmonary resuscitation. The findings provide resuscitation teams, patients, and their surrogates with insights into the likelihood of favorable outcomes if patients pending the first return of spontaneous circulation continue to receive further cardiopulmonary resuscitation., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organization for the submitted work other than that described above; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

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: 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.)

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

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

Background: Global longitudinal strain (GLS) is an echocardiographic method to identify left ventricular (LV) dysfunction after cardiac arrest that is less sensitive to loading conditions. We aimed to identify the frequency of impaired GLS following pediatric cardiac arrest, and its association with hospital mortality., Methods: This is a retrospective single-center cohort study of children <18 years of age treated in the pediatric intensive care unit (PICU) after in- or out-of-hospital cardiac arrest (IHCA and OHCA), with echocardiogram performed within 24 hours of initiation of post-arrest PICU care between 2013 and 2020. Patients with congenital heart disease, post-arrest extracorporeal support, or inability to measure GLS were excluded. Echocardiographic LV ejection fraction (EF) and shortening fraction (SF) were abstracted from the chart. GLS was measured post hoc; impaired strain was defined as LV GLS ≥ 2 SD worse than age-dependent normative values. Demographics and pre-arrest, arrest, and post-arrest characteristics were compared between subjects with normal versus impaired GLS. Correlation between GLS, SF and EF were calculated with Pearson comparison. Logistic regression tested the association of GLS with mortality. Area under the receiver operator curve (AUROC) was calculated for discriminative utility of GLS, EF, and SF with mortality., Results: GLS was measured in 124 subjects; impaired GLS was present in 46 (37.1%). Subjects with impaired GLS were older (median 7.9 vs. 1.9 years, p < 0.001), more likely to have ventricular tachycardia/fibrillation as initial rhythm (19.6% versus 3.8%, p = 0.017) and had higher peak troponin levels in the first 24 hours post-arrest (median 2.5 vs. 0.5, p = 0.002). There were no differences between arrest location or CPR duration by GLS groups. Subjects with impaired GLS compared to normal GLS had lower median EF (42.6% versus 62.3%) and median SF (23.3% versus 36.6%), all p < 0.001, with strong inverse correlation between GLS and EF (rho -0.76, p < 0.001) and SF (rho -0.71, p < 0.001). Patients with impaired GLS had higher rates of mortality (60% vs. 32%, p = 0.009). GLS was associated with mortality when controlling for age and initial rhythm [aOR 1.17 per 1% increase in GLS (95% CI 1.09-1.26), p < 0.001]. GLS, EF and SF had similar discrimination for mortality: GLS AUROC 0.69 (95% CI 0.60-0.79); EF AUROC 0.71 (95% CI 0.58-0.88); SF AUROC 0.71 (95% CI 0.61-0.82), p = 0.101., Conclusions: Impaired LV function as measured by GLS after pediatric cardiac arrest is associated with hospital mortality. GLS is a novel complementary metric to traditional post-arrest echocardiography that correlates strongly with EF and SF and is associated with mortality. Future large prospective studies of post-cardiac arrest care should investigate the prognostic utilities of GLS, alongside SF and EF., 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: 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.)

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.)

Background Current pediatric cardiac arrest guidelines recommend depressing the chest by one-third anterior-posterior diameter (APD), which is presumed to equate to absolute age-specific chest compression depth targets (4 cm for infants and 5 cm for children). However, no clinical studies during pediatric cardiac arrest have validated this presumption. We aimed to study the concordance of measured one-third APD with absolute age-specific chest compression depth targets in a cohort of pediatric patients with cardiac arrest. Methods and Results This was a retrospective observational study from a multicenter, pediatric resuscitation quality collaborative (pediRES-Q [Pediatric Resuscitation Quality Collaborative]) from October 2015 to March 2022. In-hospital patients with cardiac arrest ≤12 years old with APD measurements recorded were included for analysis. One hundred eighty-two patients (118 infants >28 days old to <1 year old, and 64 children 1 to 12 years old) were analyzed. The mean one-third APD of infants was 3.2 cm (SD, 0.7 cm), which was significantly smaller than the 4 cm target depth ( P <0.001). Seventeen percent of the infants had one-third APD measurements within the 4 cm ±10% target range. For children, the mean one-third APD was 4.3 cm (SD, 1.1 cm). Thirty-nine percent of children had one-third APD within the 5 cm ±10% range. Except for children 8 to 12 years old and overweight children, the measured mean one-third APD of the majority of the children was significantly smaller than the 5 cm depth target ( P <0.05). Conclusions There was poor concordance between measured one-third APD and absolute age-specific chest compression depth targets, particularly for infants. Further study is needed to validate current pediatric chest compression depth targets and evaluate the optimal chest compression depth to improve cardiac arrest outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02708134.

Aims: The primary objective was to determine the association between clinician-reported use of end-tidal CO2 (ETCO2) or diastolic blood pressure (DBP) to monitor cardiopulmonary resuscitation (CPR) quality during pediatric in-hospital cardiac arrest (pIHCA) and survival outcomes., Design: A retrospective cohort study was performed in two cohorts: (1) Patients with an invasive airway in place at the time of arrest to evaluate ETCO2 use, and (2) patients with an arterial line in place at the time of arrest to evaluate DBP use. The primary exposure was clinician-reported use of ETCO2 or DBP. The primary outcome was return of spontaneous circulation (ROSC). Propensity-weighted logistic regression evaluated the association between monitoring and outcomes., Setting: Hospitals reporting to the American Heart Association's Get With The Guidelines®- Resuscitation registry (2007-2021)., Patients: Children with index IHCA with an invasive airway or arterial line at the time of arrest., Results: Between January 2007 and May 2021, there were 15,280 pediatric CPR events with an invasive airway or arterial line in place at the time of arrest. Of 7159 events with an invasive airway, 6829 were eligible for analysis. Of 2978 events with an arterial line, 2886 were eligible. Clinicians reported using ETCO2 in 1335/6829 (20%) arrests and DBP in 1041/2886 (36%). Neither exposure was associated with ROSC. ETCO2 monitoring was associated with higher odds of 24-hour survival (aOR 1.17 [1.02, 1.35], p = 0.03)., Conclusions: Neither clinician-reported ETCO2 monitoring nor DBP monitoring during pIHCA were associated with ROSC. Monitoring of ETCO2 was associated with 24-hour survival., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Vinay Nadkarni is a member of the Editorial Board of Resuscitation., (Copyright © 2023. Published by Elsevier B.V.)

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

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

Background The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22- to 24-hour survival with extracorporeal life support, and secondarily to evaluate differences in neurologic injury. Methods and Results Ten-kilogram, 4-week-old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof-of-concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0-6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra-abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group ( P =0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 [IQR 7.4-7.4] versus CPR30: 7.5 [IQR 7.4-7.5], P =0.022), higher lactate (CPR60: 6.8 [IQR 6.8-11] versus CPR30: 4.2 [IQR 4.1-4.3] mmol/L; P =0.012), and higher ICP (CPR60: 19.3 [IQR 11.7-29.3] versus CPR30: 7.9 [IQR 6.7-9.3] mm Hg; P =0.037). Both groups had greater mitochondrial injury than shams (CPR60: P <0.001; CPR30: P <0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24-hour survival with more severe lactic acidosis in the 60-minute cohort.

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 and Objectives: Diffusion MRI can quantify the extent of hypoxic-ischemic brain injury after cardiac arrest. Our objective was to determine the association between the adult-derived threshold of apparent diffusion coefficient (ADC) <650 × 10 -6 mm 2 /s in >10% of brain tissue and an unfavorable outcome after pediatric cardiac arrest. Since ADC decreases exponentially as a function of increasing age, we determined the association between (1) having >10% of brain tissue below a novel age-dependent ADC threshold, and (2) age-normalized whole-brain mean ADC and unfavorable outcome., Methods: This was a retrospective study of patients aged ≤18 years who had cardiac arrest and a clinically obtained brain MRI within 7 days. The primary outcome was unfavorable neurologic status at hospital discharge based on the Pediatric Cerebral Performance Category score. ADC images were extracted from 3-direction diffusion imaging. We determined whether each patient had >10% of voxels with an ADC below prespecified thresholds. We computed the whole-brain mean ADC for each patient., Results: One hundred thirty-four patients were analyzed. Patients with ADC <650 × 10 -6 mm 2 /s in >10% of voxels had 15 times higher odds (95% CI 5-65) of an unfavorable outcome compared with patients with ADC <650 × 10 -6 mm 2 /s (area under the receiver operating characteristic curve [AUROC] 0.72 [95% CI 0.63-0.80]). These ADC criteria had a sensitivity and specificity of 0.49 and 0.94, respectively, and positive and negative predictive values of 0.93 and 0.52, respectively, for an unfavorable outcome. The age-dependent ADC threshold that yielded optimal sensitivity and specificity for unfavorable outcomes was <300 × 10 -6 mm 2 /s below each patient's predicted whole-brain mean ADC. The sensitivity, specificity, and positive and negative predictive values for this ADC threshold were 0.53, 0.96, 0.96, and 0.54, respectively (odds ratio [OR] 26.4 [95% CI 7.5-168.3]; AUROC 0.74 [95% CI 0.66-0.83]). Lower age-normalized whole-brain mean ADC was also associated with an unfavorable outcome (OR 0.42 [0.24-0.64], AUROC 0.76 [95% CI 0.66-0.82])., Discussion: Quantitative diffusion thresholds on MRI within 7 days after cardiac arrest were associated with an unfavorable outcome in children. The age-independent ADC threshold was highly specific for predicting an unfavorable outcome. However, the specificity and sensitivity increased when using age-dependent ADC thresholds. Age-dependent ADC thresholds may improve prognostic accuracy and require further investigation in larger cohorts., Classification of Evidence: This study provides Class III evidence that quantitative diffusion-weighted imaging within 7 days postarrest can predict an unfavorable clinical outcome in children., (© 2022 American Academy of Neurology.)

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.)

This article aims to provide guidance to health care workers for the provision of basic and advanced life support to children and neonates with suspected or confirmed coronavirus disease 2019 (COVID-19). It aligns with the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular care while providing strategies for reducing risk of transmission of severe acute respiratory syndrome coronavirus 2 to health care providers. Patients with suspected or confirmed COVID-19 and cardiac arrest should receive chest compressions and defibrillation, when indicated, as soon as possible. Because of the importance of ventilation during pediatric and neonatal resuscitation, oxygenation and ventilation should be prioritized. All CPR events should therefore be considered aerosol-generating procedures. Thus, personal protective equipment (PPE) appropriate for aerosol-generating procedures (including N95 respirators or an equivalent) should be donned before resuscitation, and high-efficiency particulate air filters should be used. Any personnel without appropriate PPE should be immediately excused by providers wearing appropriate PPE. Neonatal resuscitation guidance is unchanged from standard algorithms, except for specific attention to infection prevention and control. In summary, health care personnel should continue to reduce the risk of severe acute respiratory syndrome coronavirus 2 transmission through vaccination and use of appropriate PPE during pediatric resuscitations. Health care organizations should ensure the availability and appropriate use of PPE. Because delays or withheld CPR increases the risk to patients for poor clinical outcomes, children and neonates with suspected or confirmed COVID-19 should receive prompt, high-quality CPR in accordance with evidence-based guidelines., (Copyright © 2022 by the American Academy of Pediatrics.)

Aim: Cardiac arrest often results in severe neurologic injury. Improving care for these patients is difficult as few noninvasive biomarkers exist that allow physicians to monitor neurologic health. The amount of low-frequency power (LFP, 0.01-0.1 Hz) in cerebral haemodynamics has been used in functional magnetic resonance imaging as a marker of neuronal activity. Our hypothesis was that increased LFP in cerebral blood flow (CBF) would be correlated with improvements in invasive measures of neurologic health., Methods: We adapted the use of LFP for to monitoring of CBF with diffuse correlation spectroscopy. We asked whether LFP (or other optical biomarkers) correlated with invasive microdialysis biomarkers (lactate-pyruvate ratio - LPR - and glycerol concentration) of neuronal injury in the 4 h after return of spontaneous circulation in a swine model of paediatric cardiac arrest (Sus scrofa domestica, 8-11 kg, 51% female). Associations were tested using a mixed linear effects model., Results: We found that higher LFP was associated with higher LPR and higher glycerol concentration. No other biomarkers were associated with LPR; cerebral haemoglobin concentration, oxygen extraction fraction, and one EEG metric were associated with glycerol concentration., Conclusion: Contrary to expectations, higher LFP in CBF was correlated with worse invasive biomarkers. Higher LFP may represent higher neurologic activity, or disruptions in neurovascular coupling. Either effect may be harmful in the acute period after cardiac arrest. Thus, these results suggest our methodology holds promise for development of new, clinically relevant biomarkers than can guide resuscitation and post-resuscitation care. Institutional protocol number: 19-001327., (Copyright © 2022. Published by Elsevier B.V.)

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

Background: Guidelines for depth of chest compressions in pediatric cardiopulmonary resuscitation (CPR) are based on sparse evidence., Objective: We sought to evaluate the performance of the two most widely recommended chest compression depth levels for pediatric CPR (1.5 in. and 1/3 the anterior-posterior diameter- APd) in a controlled swine model of asphyxial cardiac arrest., Methods: We executed a 2-group, randomized laboratory study with an adaptive design allowing early termination for overwhelming injury or benefit. Forty mixed-breed domestic swine (mean weight = 26 kg) were sedated, anesthetized and paralyzed along with endotracheal intubation and mechanical ventilation. Asphyxial cardiac arrest was induced with fentanyl overdose. Animals were untreated for 9 min followed by mechanical CPR with a target depth of 1.5 in. or 1/3 the APd. Advanced life support drugs were administered IV after 4 min of basic resuscitation followed by defibrillation at 14 min. The primary outcomes were return of spontaneous circulation (ROSC), hemodynamics and CPR-related injury severity., Results: Enrollment in the 1/3 APd group was stopped early due to overwhelming differences in injury. Twenty-three animals were assigned to the 1.5 in. group and 15 assigned to the 1/3 APd group, per an adaptive group design. The 1/3 APd group had increased frequency of rib fracture (6.7 vs 1.7, p < 0.001) and higher proportions of several anatomic injury markers than the 1.5 in. group, including sternal fracture, hemothorax and blood in the endotracheal tube (p < 0.001). ROSC and hemodynamic measures were similar between groups., Conclusion: In this pediatric model of cardiac arrest, chest compressions to 1/3APd were more harmful without a concurrent benefit for resuscitation outcomes compared to the 1.5 in. compression group., Competing Interests: Declaration of Competing Interest Dr. Salcido performs fee-for-service work for ZOLL Medical. Drs. Salcido and Menegazzi hold a patent on a system for cardiopulmonary resuscitation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: To determine the prevalence of pulmonary hypertension (PH) among children with in-hospital cardiac arrest (IHCA) and its association with survival., Methods: Children (<18 years) admitted to ICUs participating in the Virtual Pediatric Systems multicenter registry between January 2011 and December 2017 who had an IHCA during their hospitalization were included. Patients were classified by whether they had a documented diagnosis of PH at the time of IHCA. Clinical characteristics were compared between patients with and without PH. After propensity score matching, conditional logistic regression within the matched cohort determined the association between PH and survival to hospital discharge., Results: Of 18,575 children with IHCA during the study period, 1,590 (8.6%) had a pre-arrest diagnosis of PH. Patients with PH were more likely to be 29 days to 2 years of age, female, Black/African American, and American Indian/Alaskan Native, and to be treated in a cardiac ICU or mixed PICU/cardiac ICU. At ICU admission, PH patients had a lower probability of death as determined by the Pediatric Index of Mortality 2 (PIM-2) score. Patients with PH were more likely to be receiving inhaled nitric oxide (13.0% vs. 2.1%; p < 0.001). Propensity score matching successfully matched 1,302 PH patients with 3,604 non-PH patients. Patients with PH were less likely to survive to hospital discharge (aOR 0.83; 95% CI: 0.72-0.95; p = 0.01) than non-PH patients., Conclusions: In this large multicenter study, 8.6% of children with IHCA had pre-existing documented PH. These children were less likely to survive to hospital discharge than those without PH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: Animal studies of cardiac arrest suggest that shorter epinephrine dosing intervals than currently recommended (every 3-5 min) may be beneficial in select circumstances. Objectives: To evaluate the association between epinephrine dosing intervals and pediatric cardiac arrest outcomes. Methods: Single-center retrospective cohort study of children (<18 years of age) who received ⩾1 minute of cardiopulmonary resuscitation and ⩾2 doses of epinephrine for an index in-hospital cardiac arrest. Exposure was epinephrine dosing interval ⩽2 minutes (frequent epinephrine) versus >2 minutes. The primary outcome was survival to hospital discharge with a favorable neurobehavioral outcome (Pediatric Cerebral Performance Category score 1-2 or unchanged). Logistic regression evaluated the association between dosing interval and outcomes; additional analyses explored duration of cardiopulmonary resuscitation (CPR) as a mediator. In a subgroup, the effect of dosing interval on diastolic blood pressure was investigated. Measurements and Main Results: Between January 2011 and December 2018, 125 patients met inclusion/exclusion criteria; 33 (26%) received frequent epinephrine. Frequent epinephrine was associated with increased odds of survival with favorable neurobehavioral outcome (adjusted odds ratio, 2.56; 95% confidence interval, 1.07-6.14; P  = 0.036), with 66% of the association mediated by CPR duration. Delta diastolic blood pressure was greater after the second dose of epinephrine among patients who received frequent epinephrine (median [interquartile range], 6.3 [4.1 to 16.9] vs. 0.13 [-2.3 to 1.9] mm Hg; P  = 0.034). Conclusions: In patients who received at least two doses of epinephrine, dosing intervals ⩽2 minutes were associated with improved neurobehavioral outcomes compared with dosing intervals >2 minutes. Mediation analysis suggests that improved outcomes are largely due to frequent epinephrine shortening duration of CPR.

Aims: Assessment of brain injury severity early after cardiac arrest (CA) may guide therapeutic interventions and help clinicians counsel families regarding neurologic prognosis. We aimed to determine whether adding EEG features to predictive models including clinical variables and examination signs increased the accuracy of short-term neurobehavioral outcome prediction., Methods: This was a prospective, observational, single-center study of consecutive infants and children resuscitated from CA. Standardized EEG scoring was performed by an electroencephalographer for the initial EEG timepoint after return of spontaneous circulation (ROSC) and each 12-h segment from the time of ROSC up to 48 h. EEG Background Category was scored as: (1) normal; (2) slow-disorganized; (3) discontinuous or burst-suppression; or (4) attenuated-featureless. The primary outcome was neurobehavioral outcome at discharge from the Pediatric Intensive Care Unit. To develop the final predictive model, we compared areas under the receiver operating characteristic curves (AUROC) from models with varying combinations of Demographic/Arrest Variables, Examination Signs, and EEG Features., Results: We evaluated 89 infants and children. Initial EEG Background Category was normal in 9 subjects (10%), slow-disorganized in 44 (49%), discontinuous or burst suppression in 22 (25%), and attenuated-featureless in 14 (16%). The final model included Demographic/Arrest Variables (witnessed status, doses of epinephrine, initial lactate after ROSC) and EEG Background Category which achieved AUROC of 0.9 for unfavorable neurobehavioral outcome and 0.83 for mortality., Conclusions: The addition of standardized EEG Background Categories to readily available CA variables significantly improved early stratification of brain injury severity after pediatric CA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Guideline deviations with impact on patient outcomes frequently occur during in-hospital cardiopulmonary resuscitation (CPR). However, barriers and facilitators for preventing these guideline deviations are understudied. We aimed to characterize challenges occurring during IHCA and identify barriers and facilitators perceived by actual team members immediately following IHCA events., Methods: This was a prospective multicenter clinical study. Following each resuscitation attempt in 6 hospitals over a 4-year period, we immediately sent web-based structured questionnaires to all responding team members, reporting their perceived resuscitation quality, teamwork, and communication and what they perceived as barriers or facilitators. Comments were analyzed using qualitative inductive thematic analysis methodology., Results: We identified 924 resuscitation attempts and 3,698 survey responses were collected including 2,095 qualitative comments (response rate: 65%). Most frequent challenges were overcrowding (27%) and poor ergonomics/choreography of people in the room (17%). Narrative comments aligned into 24 unique barrier and facilitator themes in 4 domains: 6 related to treatment (most prevalent: CPR, rhythm check, equipment), 7 for teamwork (most prevalent: role allocation, crowd control, collaboration with ward staff), 6 for leadership (most prevalent: visible and distinct leader, multiple leaders, leader experience), and 5 for communication (most prevalent: closed loops, atmosphere in room, speaking loud/clear)., Conclusion: Using novel, immediate after-event survey methodology of individual cardiac arrest team members, we characterized challenges and identified 24 themes within 4 domains that were barriers and facilitators for in-hospital resuscitation teams. We believe this level of detail is necessary to contextualize guidelines and training to facilitate high-quality resuscitation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: Inhaled nitric oxide (iNO) during cardiopulmonary resuscitation (CPR) improved systemic hemodynamics and outcomes in a preclinical model of adult in-hospital cardiac arrest (IHCA) and may also have a neuroprotective role following cardiac arrest. The primary objectives of this study were to determine if iNO during CPR would improve cerebral hemodynamics and mitochondrial function in a pediatric model of lipopolysaccharide-induced shock-associated IHCA., Methods: After lipopolysaccharide infusion and ventricular fibrillation induction, 20 1-month-old piglets received hemodynamic-directed CPR and were randomized to blinded treatment with or without iNO (80 ppm) during and after CPR. Defibrillation attempts began at 10 min with a 20-min maximum CPR duration. Cerebral tissue from animals surviving 1-h post-arrest underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and immunohistochemical analyses to assess neuropathology., Results: During CPR, the iNO group had higher mean aortic pressure (41.6 ± 2.0 vs. 36.0 ± 1.4 mmHg; p = 0.005); diastolic BP (32.4 ± 2.4 vs. 27.1 ± 1.7 mmHg; p = 0.03); cerebral perfusion pressure (25.0 ± 2.6 vs. 19.1 ± 1.8 mmHg; p = 0.02); and cerebral blood flow relative to baseline (rCBF: 243.2 ± 54.1 vs. 115.5 ± 37.2%; p = 0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O 2 /s mg; p = 0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O 2 /s mg; p = 0.02). There were no other differences in mitochondrial respiration or brain injury between groups., Conclusions: Treatment with iNO during CPR resulted in superior systemic hemodynamics, rCBF, and cerebral mitochondrial Complex I respiration in this pediatric cardiac arrest model., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Neurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO 2 ], [Hb]), oxygen saturation (StO 2 ) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8-11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (J w , w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO 2 ], StO 2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO 2 ] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.

Aims: To describe trends in pediatric in-hospital cardiac arrest drug administration and to assess temporal associations of the Pediatric Advanced Life Support (PALS) guideline changes with drug usage., Methods: Pediatric patients <18 years old with in-hospital cardiac arrest recorded in the American Heart Association Get With The Guidelines-Resuscitation database between 2002 and 2018 were included. The annual adjusted odds of receiving each intra-arrest medication was determined. The association between changes in the PALS Guidelines and medication use over time was assessed interrupted time series analyses., Results: A total of 6107 patients were analyzed. The adjusted odds of receiving lidocaine (0.33; 95% CI, 0.18, 0.61; p < 0.001), atropine (0.19; 95% CI 0.12, 0.30; p < 0.001) and bicarbonate (0.54; 95% CI 0.35, 0.86; p = 0.009) were lower in 2018 compared to 2002. For lidocaine, there were no significant changes in the step (-2.1%; 95% CI, -5.9%, 1.6%; p = 0.27) after the 2010 or 2015 (Step: -1.5%; 95% CI, -8.0%, 5.0; p = 0.65) guideline releases. There were no significant changes in the step for bicarbonate (-2.3%; 95% CI, -7.6%, 3.0%; p = 0.39) after the 2010 updates. For atropine, there was a downward step change after the 2010 guideline release (-5.9%; 95% CI, -10.5%, -1.3%; p = 0.01)., Conclusions: Changes to the PALS guidelines for lidocaine and bicarbonate were not temporally associated with acute changes in the use of these medications; however, better alignment with these updates was observed over time. A minor update to the language surrounding atropine in the PALS text was associated with a modest acute change in the observed use of atropine. Future studies exploring other factors that influence prescribers in pediatric IHCA are needed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: While most pediatric coronavirus disease 2019 cases are not life threatening, some children have severe disease requiring emergent resuscitative interventions. Resuscitation events present risks to healthcare provider safety and the potential for compromised patient care. Current resuscitation practices and policies for children with suspected/confirmed coronavirus disease 2019 are unknown., Design: Multi-institutional survey regarding inpatient resuscitation practices during the coronavirus disease 2019 pandemic., Setting: Internet-based survey., Subjects: U.S. PICU representatives (one per institution) involved in resuscitation system planning and oversight., Interventions: None., Measurements and Main Results: Of 130 institutions surveyed, 78 (60%) responded. Forty-eight centers (62%) had admitted coronavirus disease 2019 patients; 26 (33%) reported code team activation for patients with suspected/confirmed coronavirus disease 2019. Sixty-seven respondents (86%) implemented changes to inpatient emergency response systems. The most common changes were as follows: limited number of personnel entering patient rooms (75; 96%), limited resident involvement (71; 91%), and new or refined team roles (74; 95%). New or adapted technology is being used for coronavirus disease 2019 resuscitations in 58 centers (74%). Most institutions (57; 73%) are using enhanced personal protective equipment for all coronavirus disease 2019 resuscitation events; 18 (23%) have personal protective equipment policies dependent on the performance of aerosol generating procedures. Due to coronavirus disease 2019, most respondents are intubating earlier during cardiopulmonary resuscitation (56; 72%), utilizing video laryngoscopy (67; 86%), pausing chest compressions during laryngoscopy (56; 72%), and leaving patients connected to the ventilator during cardiopulmonary resuscitation (56; 72%). Responses were varied regarding airway personnel, prone cardiopulmonary resuscitation, ventilation strategy during cardiopulmonary resuscitation without an airway in place, and extracorporeal cardiopulmonary resuscitation. Most institutions (46; 59%) do not have policies regarding limitations of resuscitation efforts in coronavirus disease 2019 patients., Conclusions: Most U.S. pediatric institutions rapidly adapted their resuscitation systems and practices in response to the coronavirus disease 2019 pandemic. Changes were commonly related to team members and roles, personal protective equipment, and airway and breathing management, reflecting attempts to balance quality resuscitation with healthcare provider safety.

The American Heart Association (AHA) recommends first defibrillation energy dose of 2 Joules/kilogram (J/kg) for pediatric cardiac arrest with ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT). However, optimal first energy dose remains unclear., Methods: Using AHA Get With the Guidelines-Resuscitation® (GWTG-R) database, we identified children ≤12 years with IHCA due to VF/pVT. Primary exposure was energy dose in J/kg. We categorized energy doses: 1.7-2.5 J/kg as reference (reflecting 2 J/kg intended dose), <1.7 J/kg and >2.5 J/kg. We compared survival for reference doses to all other doses. We constructed models to test association of energy dose with survival; adjusting for age, location, illness category, initial rhythm and vasoactive medications., Results: We identified 301 patients ≤12 years with index IHCA and initial VF/pVT. Survival to discharge was significantly lower with energy doses other than 1.7-2.5 J/kg. Individual dose categories of <1.7 J/kg or >2.5 J/kg were not associated with differences in survival. For patients with initial VF, doses >2.5 J/kg had worse survival compared to reference. For all patients ≤18 years (n = 422), there were no differences in survival between dosing categories. However, all ≤18 with initial VF receiving >2.5 J/kg had worse survival., Conclusions: First energy doses other than 1.7-2.5 J/kg are associated with lower rate of survival to hospital discharge in patients ≤12 years old with initial VF/pVT, and first doses >2.5 J/kg had lower survival rates in all patients ≤18 years old with initial VF. These results support current AHA guidelines for first pediatric defibrillation energy dose of 2 J/kg., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Patients who suffer in-hospital cardiac arrest (IHCA) are less likely to survive if the arrest occurs during nighttime versus daytime. Diastolic blood pressure (DBP) as a measure of chest compression quality was associated with survival from pediatric IHCA. We hypothesized that DBP during CPR for IHCA is lower during nighttime versus daytime., Methods: This is a secondary analysis of data collected from the Pediatric Intensive Care Quality of Cardiopulmonary Resuscitation Study. Pediatric or Pediatric Cardiac Intensive Care Unit patients who received chest compressions for ≥1 min and who had invasive arterial BP monitoring were enrolled. Nighttime was defined as 11:00PM to 6:59AM and daytime as 7:00AM until 10:59PM. Primary outcome was attainment of DBP ≥ 25 mmHg in infants <1 year and ≥30 mmHg in older children. Secondary outcomes were mean DBP, ROSC, and survival to hospital discharge. Univariable and multivariate analyses evaluated the relationships between time (nighttime vs. daytime) and outcomes., Results: Between July 1, 2013 and June 30, 2016, 164 arrests met all inclusion/exclusion criteria: 45(27%) occurred at nighttime and 119(73%) during daytime. Average DBPs achieved were not different between groups (DBP: nighttime 28.3 mmHg[25.3, 36.5] vs. daytime 29.6 mmHg[21.8, 38.0], p = 0.64). Relative risk of DBP threshold met during nighttime vs. daytime was 1.27, 95%CI [0.80, 1.98], p = 0.30. There was no significant nighttime vs. daytime difference in ROSC (28/45[62%] vs. 84/119[71%] p = 0.35) or survival to hospital discharge (16/45[36%] vs. 61/119[51%], p = 0.08)., Conclusions: In this cohort of pediatric ICU patients with IHCA, there was no significant difference in DBP during CPR between nighttime and daytime., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To characterize neurofilament light levels in children who achieved return of spontaneous circulation following cardiac arrest compared with healthy controls and determine an association between neurofilament light levels and clinical outcomes., Design: Retrospective cohort study., Setting: Academic quaternary PICU., Patients: Children with banked plasma samples from an acute respiratory distress syndrome biomarker study who achieved return of spontaneous circulation after a cardiac arrest and healthy controls., Interventions: None., Measurements and Main Results: Neurofilament light levels were determined with a highly sensitive single molecule array digital immunoassay. Patients were categorized into survivors and nonsurvivors and into favorable (Pediatric Cerebral Performance Category score of 1-2 or unchanged from baseline) or unfavorable (Pediatric Cerebral Performance Category score of 3-6 or Pediatric Cerebral Performance Category score change ≥1 from baseline). Associations between neurofilament light level and outcomes were determined using Wilcoxon rank-sum test. We enrolled 32 patients with cardiac arrest and 18 healthy controls. Demographics, severity of illness, and baseline Pediatric Cerebral Performance Category scores were similar between survivors and nonsurvivors. Healthy controls had lower median neurofilament light levels than patients after cardiac arrest (5.5 [interquartile range 5.0-8.2] vs 31.0 [12.0-338.6]; p < 0.001). Neurofilament light levels were higher in nonsurvivors than survivors (78.5 [26.2-509.1] vs 12.4 [10.3-28.2]; p = 0.012) and higher in survivors than healthy controls (p = 0.009). The four patients who survived with a favorable outcome had neurofilament light levels that were not different from patients with unfavorable outcomes (21.9 [8.5--35.7] vs 37.2 [15.4-419.1]; p = 0.60) although two of the four patients who survived with favorable outcomes had progressive encephalopathies with both baseline and postcardiac arrest Pediatric Cerebral Performance Category scores of 4., Conclusions: Neurofilament light is a blood biomarker of hypoxic-ischemic brain injury and may help predict survival and neurologic outcome after pediatric cardiac arrest. Further study in a larger, dedicated cardiac arrest cohort with serial longitudinal measurements is warranted.

Background: Although in-hospital pediatric cardiac arrests and cardiopulmonary resuscitation occur >15,000/year in the US, few studies have assessed which factors affect the course of resuscitation in these patients. We investigated transitions from Pulseless Electrical Activity (PEA) to Ventricular Fibrillation/pulseless Ventricular Tachycardia (VF/pVT), Return of Spontaneous Circulation (ROSC) and recurrences from ROSC to PEA in children and adolescents with in-hospital cardiac arrest., Methods: Episodes of cardiac arrest at the Children's Hospital of Philadelphia were prospectively registered. Defibrillators that recorded chest compression depth/rate and ventilation rate were applied. CPR variables, patient characteristics and etiology, and dynamic factors (e.g. the proportion of time spent in PEA or ROSC) were entered as time-varying covariates for the transition intensities under study., Results: In 67 episodes of CPR in 59 patients (median age 15 years) with cardiac arrest, there were 52 transitions from PEA to ROSC, 22 transitions from PEA to VF/pVT, and 23 recurrences of PEA from ROSC. Except for a nearly significant effect of mean compression depth beyond a threshold of 5.7 cm, only dynamic factors that evolved during CPR favored a transition from PEA to ROSC. The latter included a lower proportion of PEA over the last 5 min and a higher proportion of ROSC over the last 5 min. Factors associated with PEA to VF/pVT development were age, weight, the proportion spent in VF/pVT or PEA the last 5 min, and the general transition intensity, while PEA recurrence from ROSC only depended on the general transition intensity., Conclusion: The clinical course during pediatric cardiac arrest was mainly influenced by dynamic factors associated with time in PEA and ROSC. Transitions from PEA to ROSC seemed to be favored by deeper compressions., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

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

Background Hyperoxia during cardiopulmonary resuscitation (CPR) may lead to oxidative injury from mitochondrial-derived reactive oxygen species, despite guidelines recommending 1.0 inspired oxygen during CPR. We hypothesized exposure to 1.0 inspired oxygen during CPR would result in cerebral hyperoxia, higher mitochondrial-derived reactive oxygen species, increased oxidative injury, and similar survival compared with those exposed to 21% oxygen. Methods and Results Four-week-old piglets (n=25) underwent asphyxial cardiac arrest followed by randomization and blinding to CPR with 0.21 (n=10) or 1.0 inspired oxygen (n=10) through 10 minutes post return of spontaneous circulation. Sham was n=5. Survivors received 4 hours of protocolized postarrest care, whereupon brain was obtained for mitochondrial analysis and neuropathology. Groups were compared using Kruskal-Wallis test, Wilcoxon rank-sum test, and generalized estimating equations regression models. Both 1.0 and 0.21 groups were similar in systemic hemodynamics and cerebral blood flow, as well as survival (8/10). The 1.0 animals had relative cerebral hyperoxia during CPR and immediately following return of spontaneous circulation (brain tissue oxygen tension, 85% [interquartile range, 72%-120%] baseline in 0.21 animals versus 697% [interquartile range, 515%-721%] baseline in 1.0 animals; P =0.001 at 10 minutes postarrest). Cerebral mitochondrial reactive oxygen species production was higher in animals treated with 1.0 compared with 0.21 ( P <0.03). Exposure to 1.0 oxygen led to increased cerebral oxidative injury to proteins and lipids, as evidenced by significantly higher protein carbonyls and 4-hydroxynoneals compared with 0.21 ( P <0.05) and sham ( P <0.001). Conclusions Exposure to 1.0 inspired oxygen during CPR caused cerebral hyperoxia during resuscitation, and resultant increased mitochondrial-derived reactive oxygen species and oxidative injury following cardiac arrest.