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Sinusitis in patients with human immunodeficiency virus (HIV) infection usually arises from the same organisms that are infective in the nonimmunosuppressed population. The authors of this article report that optimal antimicrobial treatment and functional endoscopic sinus surgery failed to eradicate sinonasal disease in three of five patients with acquired immunodeficiency syndrome (AIDS) and refractory sinusitis. The sinonasal disease was manifested by congested, edematous, and polypoid mucosa, often with a superimposed bacterial infection from ostial obstruction. After tissue was sent for electron microscopy (EM), the patients were eventually diagnosed with microsporidiosis of the sinonasal cavities. Microsporidia are obligate intracellular protozoans that have been seen in AIDS patients with diarrhea. These protozoans have only recently been identified in sinonasal tissue. Microsporidia are often missed on routine histopathology. The authors present case reports on their five AIDS patients with refractory sinusitis. The management of refractory sinusitis in the HIV-infected population, including mandatory EM of sinonasal tissue, is also discussed. [ABSTRACT FROM AUTHOR]

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

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.

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: 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: 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.)

Physicians are experiencing epidemic levels of work-related stress and burnout. Determine efficacy of mindfulness meditation delivered as a hybrid (in-person and digital) format to reduce perceived stress in pediatric residents. Pediatric residents (n = 66) were block randomized to a hybrid Mindful Awareness Practices (MAPs) intervention, comprised of one in-person 60-min session and 6-week access to a digitally delivered MAPs curriculum (n = 27) or wait-list control (n = 39). Perceived Stress Scale (PSS) was administered at baseline and post-intervention as the primary outcome measure. A priori secondary outcomes were measured using the Abbreviated Maslach Burnout Inventory-9, Beck Depression Inventory, Beck Anxiety Inventory, UCLA Loneliness Scale, and Pittsburgh Sleep Quality Index. After the first session, 58% participated at least one digital session (M = 2.0; SD = 1.3). MAPs participants showed significant decrease in PSS compared to controls, with between-group mean difference of 2.20 (95% CI 0.47-3.93) at post-intervention (effect size 0.91; 0.19-1.62). No secondary outcome group differences were detected. Exposure to a hybrid mindfulness intervention was associated with improvement in perceived stress among pediatric residents.Trial Registration: NCT03613441., (© 2022. The Author(s).)

Fluid restriction and diuretic management are mainstays in the postoperative management of cardiac patients, at risk of volume overload and its deleterious effects on primary cardiac function and multi-organ systems. The importance of fluid homeostasis is further emphasized among orthotopic heart transplant recipients (OHT). We sought to investigate the relationship between postoperative volume overload, mortality, and allograft dysfunction among pediatric OHT recipients within 1-year of transplantation. This is a retrospective cohort study from a single pediatric OHT center. Children under 21 years undergoing cardiac transplantation between 2010 and 2018 were included. Cumulative fluid overload (cFO) was assessed as percent fluid accumulation adjusted for preoperative body weight. Greater than 10% cFO defined those with postoperative cFO and a comparison of postoperative cFO vs. no postoperative cFO (< 5%) is reported. 102 pediatric OHT recipients were included. Early cFO at 72 h post-OHT occurred in 14% and overall cFO at 1-week post-OHT occurred in 23% of patients. Risk factors for cFO included younger age, lower weight, and postoperative ECMO. Early cFO was associated with postoperative mortality at 1-year, OR 8.6 (95% CI 1.4, 51.6), p = 0.04, independent of age and weight. There was no significant relationship between cFO and allograft dysfunction, measured by rates of clinical rejection and cardiopulmonary filling pressures within 1-year of transplant. Early postoperative volume overload is prevalent and associated with increased risk of death at 1-year among pediatric OHT recipients. It may be an important postoperative marker of transplant survival, and this relationship warrants further clinical investigation., (© 2023. The Author(s).)

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: Venoarterial extracorporeal membrane oxygenation (ECMO) supports patients with advanced cardiac dysfunction; however, mortality occurs in a significant subset of patients. The authors performed a multicenter, prospective study to determine hemodynamic and echocardiographic predictors of mortality in children placed on ECMO for cardiac support., Methods: Over 8 years, six heart centers prospectively assessed echocardiographic and hemodynamic variables on full and minimum ECMO flow. Sixty-three patients were enrolled, ranging in age from 1 day to 16 years. Hemodynamic measurements included heart rate, vasoactive inotropic score, arteriovenous oxygen difference, pulse pressure, and lactate. Echocardiographic variables included shortening fraction, ejection fraction (EF), right ventricular fractional area change, outflow tract Doppler-derived stroke distance (velocity-time integral [VTI]), and degree of atrioventricular valve regurgitation. Patients were stratified into two groups: those who were able to wean within 48 hours of assessment and survived without ventricular assist devices or orthotopic heart transplantation (successful wean group) and those with unsuccessful weaning. For each patient, variables were compared between full and minimum ECMO flow for each group., Results: Thirty-eight patients (60%) formed the unsuccessful group (two with ventricular assist devices, four with orthotopic heart transplantation, 24 deaths), and 25 constituted the successful wean group. At minimum flow, higher EF (53 ± 16% vs 40 ± 20%, P = .0094), less mitral regurgitation (0.8 ± 0.9 vs 1.4 ± 0.9, P = .0329), and lower central venous pressure (12.0 ± 3.9 vs 14.7 ± 5.4 mm Hg), along with higher VTI (9.0 ± 2.9 vs 6.8 ± 3.7 cm, P = .0154), correlated successful weaning. A longer duration of ECMO (8 vs 5 days, P < .0002) was associated with unsuccessful weaning. Multivariate logistic regression predicted minimum-flow EF and VTI to independently predict successful weaning with cutoff values by receiver operating characteristic analysis of EF > 41% (area under the curve, 0.712; P = .0005) and VTI > 7.9 cm (area under the curve, 0.729; P = .0010)., Conclusions: Diminished VTI or EF during ECMO weaning predicts the need for orthotopic heart transplantation or ventricular assist device support or death in children on ECMO for cardiac dysfunction. Increased postwean central venous pressure or mitral regurgitation along with a prolonged ECMO course also predicted these adverse outcomes. These measurements should be used to help discriminate which patients will require alternative methods of circulatory support for survival., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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

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

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

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: Bleeding is a common complication of extracorporeal membrane oxygenation (ECMO) for pediatric cardiac patients. We aimed to identify anticoagulation practices, cardiac diagnoses, and surgical variables associated with bleeding during pediatric cardiac ECMO by combining two established databases, the Collaborative Pediatric Critical Care Research Network (CPCCRN) Bleeding and Thrombosis in ECMO (BATE) and the Extracorporeal Life Support Organization (ELSO) Registry. Methods: All children (<19 years) with a primary cardiac diagnosis managed on ECMO included in BATE from six centers were analyzed. ELSO Registry criteria for bleeding events included pulmonary or intracranial bleeding, or red blood cell transfusion >80 ml/kg on any ECMO day. Bleeding odds were assessed on ECMO Day 1 and from ECMO Day 2 onwards with multivariable logistic regression. Results: There were 187 children with 114 (61%) bleeding events in the study cohort. Biventricular congenital heart disease (94/187, 50%) and cardiac medical diagnoses (75/187, 40%) were most common, and 48 (26%) patients were cannulated directly from cardiopulmonary bypass (CPB). Bleeding events were not associated with achieving pre-specified therapeutic ranges of activated clotting time (ACT) or platelet levels. In multivariable analysis, elevated INR and fibrinogen were associated with bleeding events (OR 1.1, CI 1.0-1.3, p = 0.02; OR 0.77, CI 0.6-0.9, p = 0.004). Bleeding events were also associated with clinical site (OR 4.8, CI 2.0-11.1, p < 0.001) and central cannulation (OR 1.75, CI 1.0-3.1, p = 0.05) but not with cardiac diagnosis, surgical complexity, or cannulation from CPB. Bleeding odds on ECMO day 1 were increased in patients with central cannulation (OR 2.82, 95% CI 1.15-7.08, p = 0.023) and those cannulated directly from CPB (OR 3.32, 95% CI 1.02-11.61, p = 0.047). Conclusions: Bleeding events in children with cardiac diagnoses supported on ECMO were associated with central cannulation strategy and coagulopathy, but were not modulated by achieving pre-specified therapeutic ranges of monitoring assays., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ankola, Bailly, Reeder, Cashen, Dalton, Dolgner, Federman, Ghassemzadeh, Himebauch, Kamerkar, Koch, Kohne, Lewen, Srivastava, Willett and Alexander.)

Among neonatal cardiomyopathies, primary endocardial fibroelastosis (pEFE) remains a mysterious disease of the endomyocardium that is poorly genetically characterized, affecting 1/5000 live births and accounting for 25% of the entire pediatric dilated cardiomyopathy (DCM) with a devastating course and grave prognosis. To investigate the potential genetic contribution to pEFE, we performed integrative genomic analysis, using whole exome sequencing (WES) and RNA-seq in a female infant with confirmed pathological diagnosis of pEFE. Within regions of homozygosity in the proband genome, WES analysis revealed novel parent-transmitted homozygous mutations affecting three genes with known roles in cilia assembly or function. Among them, a novel homozygous variant [c.1943delA] of uncertain significance in ALMS1 was prioritized for functional genomic and mechanistic analysis. Loss of function mutations of ALMS1 have been implicated in Alstrom syndrome (AS) [OMIM 203800], a rare recessive ciliopathy that has been associated with cardiomyopathy. The variant of interest results in a frameshift introducing a premature stop codon. RNA-seq of the proband's dermal fibroblasts confirmed the impact of the novel ALMS1 variant on RNA-seq reads and revealed dysregulated cellular signaling and function, including the induction of epithelial mesenchymal transition (EMT) and activation of TGFβ signaling. ALMS1 loss enhanced cellular migration in patient fibroblasts as well as neonatal cardiac fibroblasts, while ALMS1-depleted cardiomyocytes exhibited enhanced proliferation activity. Herein, we present the unique pathological features of pEFE compared to DCM and utilize integrated genomic analysis to elucidate the molecular impact of a novel mutation in ALMS1 gene in an AS case. Our report provides insights into pEFE etiology and suggests, for the first time to our knowledge, ciliopathy as a potential underlying mechanism for this poorly understood and incurable form of neonatal cardiomyopathy. KEY MESSAGE: Primary endocardial fibroelastosis (pEFE) is a rare form of neonatal cardiomyopathy that occurs in 1/5000 live births with significant consequences but unknown etiology. Integrated genomics analysis (whole exome sequencing and RNA sequencing) elucidates novel genetic contribution to pEFE etiology. In this case, the cardiac manifestation in Alstrom syndrome is pEFE. To our knowledge, this report provides the first evidence linking ciliopathy to pEFE etiology. Infants with pEFE should be examined for syndromic features of Alstrom syndrome. Our findings lead to a better understanding of the molecular mechanisms of pEFE, paving the way to potential diagnostic and therapeutic applications., (© 2021. The Author(s).)

Objectives: To evaluate the risk factors for mortality in pediatric extracorporeal membrane oxygenation patients., Design: Retrospective, single-center study., Setting: PICU and Pediatric cardiothoracic ICU in an urban, quaternary care center., Patients: All neonatal and pediatric patients requiring extracorporeal membrane oxygenation at our institution between January 2014 and December 2018, who underwent a standardized continuous electroencephalogram neuromonitoring protocol during most of the duration of extracorporeal membrane oxygenation support. We excluded patients who had extracorporeal membrane oxygenation initiated at another institution., Intervention: None., Measurements and Main Results: Sixty-six children required extracorporeal membrane oxygenation support during this period. Four patients were excluded, three due to lack of electroencephalogram data, one with extracorporeal membrane oxygenation initiated at other institution. In the remaining 62, 11 patients (17%) had seizures, of which 5 (45%) had status epilepticus. Eight of 11 patients (72%) had exclusively electrographic seizures. A total of 33 patients (53.2%) died, of which 22 died during extracorporeal membrane oxygenation course, and one died 3 years after hospital discharge. Mean survival from extracorporeal membrane oxygenation initiation was 766.9 days (standard deviation, 691.7; median, 546.5; interquartile range 1-3, 97.7-1255.0). In multivariate analysis, increased risk of mortality was associated with the use of extracorporeal cardiopulmonary resuscitation (hazard ratio, 4.33; 95% CI, 1.75-10.72; p = 0.002), imaging findings of cerebral edema (hazard ratio, 14.31; 95% CI, 5.18-39.54; p < 0.001), high lactate level (> 100 mg/dL within 2 hr preextracorporeal membrane oxygenation) (hazard ratio, 1.22; 95% CI, 1.03-1.44; p = 0.022), and prolonged deep hypothermic circulatory arrest (hazard ratio, 3.43; 95% CI, 1.65-7.13; p < 0.001). Presence of seizures was associated with imaging findings of cerebral edema (hazard ratio, 4.16; 95% CI, 1.04-16.58; p = 0.04)., Conclusions: Seizures are common in children requiring extracorporeal membrane oxygenation support, with a high rate of electrographic seizures and status epilepticus, as in prior studies. Presence of cerebral edema is both risk factor for mortality and seizures. Other risk factors for mortality include extracorporeal cardiopulmonary resuscitation, high lactate levels, and prolonged deep hypothermic circulatory arrest.

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

Objective: To determine the effect of age of packed RBCs on tissue oxygenation in children receiving extracorporeal membrane oxygenation support., Design: A retrospective study was done between March 2013 and August 2015. The following biomarkers were examined 6 hours before and 6 hours after the conclusion of a transfusion: serum and circuit hematocrits, serum and circuit venous saturations, serum lactate levels (mg/dL), and cerebral saturation via near-infrared spectroscopy. Biomarkers were examined with respect to time relative to transfusion using four discrete categories (< 3, -3 to 0, 0-3, and > 3 hr). The association between age of blood transfusion and change in biomarkers was accessed analyzing time relative to transfusion as described above. In addition, the age of blood transfusion was analyzed similarly, using four discrete categories (0-7, 7-14, 14-21, and > 21 d)., Setting: Twenty-four bed mixed pediatric medical and cardiac ICU at a tertiary care center., Subjects: Zero- to 18-year-old patients of required extracorporeal membrane oxygenation support., Interventions: None., Measurements and Main Results: Circuit venous saturation demonstrated an increase of 2.5% (p < 0.001) in first 3 hours posttransfusion. This was followed by a 1.4% decrease after the initial 3 hours posttransfusion. Serum venous saturation showed no statistically significant change with relation to transfusions. Neither lactate levels nor near-infrared spectroscopy demonstrated any observed statistical change with relation to transfusion. With regards to the relationship between the age of RBC transfusion and tissue oxygenation biomarkers, none of the biomarkers exhibited a consistent interaction., Conclusions: Our study demonstrates that the age of packed RBC transfusion does not affect the degree tissue oxygenation in children receiving extracorporeal membrane oxygenation support, as measured by mixed venous oxygen saturation, lactate, and near-infrared spectroscopy. In addition, packed RBC transfusion, in general, did not produce any meaningful change in these markers of tissue oxygenation.

Objectives: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children., Design: Nested case-control study., Setting: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia., Patients: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness., Interventions: None., Measurements and Main Results: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia., Conclusions: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

Background: Quality of cardiopulmonary resuscitation (CPR) is associated with survival, but recommended guidelines are often not met, and less than half the children with an in-hospital arrest will survive to discharge. A single-center before-and-after study demonstrated that outcomes may be improved with a novel training program in which all pediatric intensive care unit staff are encouraged to participate in frequent CPR refresher training and regular, structured resuscitation debriefings focused on patient-centric physiology., Methods/design: This ongoing trial will assess whether a program of structured debriefings and point-of-care bedside practice that emphasizes physiologic resuscitation targets improves the rate of survival to hospital discharge with favorable neurologic outcome in children receiving CPR in the intensive care unit. This study is designed as a hybrid stepped-wedge trial in which two of ten participating hospitals are randomly assigned to enroll in the intervention group and two are assigned to enroll in the control group for the duration of the trial. The remaining six hospitals enroll initially in the control group but will transition to enrolling in the intervention group at randomly assigned staggered times during the enrollment period., Discussion: To our knowledge, this is the first implementation of a hybrid stepped-wedge design. It was chosen over a traditional stepped-wedge design because the resulting improvement in statistical power reduces the required enrollment by 9 months (14%). However, this design comes with additional challenges, including logistics of implementing an intervention prior to the start of enrollment. Nevertheless, if results from the single-center pilot are confirmed in this trial, it will have a profound effect on CPR training and quality improvement initiatives., Trial Registration: ClinicalTrials.gov, NCT02837497 . Registered on July 19, 2016.