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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.)

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.)

Aims: To identify plasma biomarkers associated with cardiac arrest in a cohort of children with acute respiratory distress syndrome (ARDS), and to assess the association of these biomarkers with mortality in children with cardiac arrest and ARDS (ARDS + CA)., Methods: This was a secondary analysis of a single-center prospective cohort study of children with ARDS from 2014-2019 with 17 biomarkers measured. Clinical characteristics and biomarkers were compared between subjects with ARDS + CA and ARDS with univariate analysis. In a sub-cohort of ARDS + CA subjects, the association between biomarker levels and mortality was tested using univariate and bivariate logistic regression., Results: Biomarkers were measured in 333 subjects: 301 with ARDS (median age 5.3 years, 55.5% male) and 32 ARDS + CA (median age 8 years, 53.1% male). More arrests (69%) occurred out-of-hospital with a median CPR duration of 11 (IQR 5.5, 25) minutes. ARDS severity, PRISM III score, vasoactive-ionotropic score and extrapulmonary organ failures were worse in the ARDS + CA versus ARDS group. Eight biomarkers were elevated in the ARDS + CA versus ARDS cohort: sRAGE, nucleosomes, SP-D, CCL22, IL-6, HSP70, IL-8, and MIP-1b. sRAGE, SP-D, and CCL22 remained elevated when the cohorts were matched for illness severity. When controlling for severity of ARDS and cardiac arrest characteristics, sRAGE, IL-6 and granzyme B were associated with mortality in the ARDS + CA group., Conclusion: sRAGE, IL-6 and granzyme B were associated with cardiac arrest mortality when controlling for illness severity. sRAGE was consistently higher in the ARDS + CA cohort compared to ARDS and retained independent association with mortality., 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 © 2021 Elsevier B.V. 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.)

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.)

Aim: To evaluate pediatric cardiopulmonary resuscitation (CPR) quality during intra-hospital transport to facilitate extracorporeal membrane oxygenation (ECMO)-CPR (ECPR). We compared chest compression (CC) rate, depth, and fraction (CCF) between the pre-transport and intra-transport periods., Methods: Observational study of children <18 years with either in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) who underwent transport between two care locations within the hospital for ECPR and who had CPR mechanics data available. Descriptive patient and arrest characteristics were summarized. The primary analysis compared pre- to intra-transport CC rate, depth, and fraction. A secondary analysis compared the proportion of pre- versus intra-transport 60-s epochs meeting guideline recommendations for rate (100-120/min), depth (≥4 cm for infants; ≥5 cm for children ≥1 year), and CCF (≥0.80)., Results: Seven patients (four IHCA; three witnessed OHCA) met eligibility criteria. Six (86%) patients survived the event and two (28%) survived to hospital discharge. Median transport CPR duration was 7 [IQR 5.5, 8.5] minutes. There were no differences in pre- vs. intra-transport CC rate (115 [113, 118] vs. 118 [114, 127] CCs/minute; p = 0.18), depth (3.2 [2.7, 4.4] vs. 3.6 [2.5, 4.6] cm; p = 0.50), or CCF (0.89 [0.82, 0.90] vs. 0.92 [0.79, 0.97]; p = 0.31). Equivalent proportions of 60-s CPR epochs met guideline recommendations between pre- and intra-transport (rate: 66% vs. 57% [p = 0.22]; depth: 14% vs. 19% [p = 0.39]; CCF: 80% vs. 75% [p = 0.43])., Conclusions: Pediatric CPR quality was maintained during intra-hospital patient transport, suggesting that it is reasonable for ECPR systems to incorporate patient transport to facilitate ECMO cannulation., (Copyright © 2020 Elsevier B.V. All rights reserved.)