Assessment of brain magnetic resonance and spectroscopy imaging findings and outcomes after pediatric cardiac arrest

IMPORTANCE: Morbidity and mortality after pediatric cardiac arrest are chiefly due to hypoxic-ischemic brain injury. Brain features seen on magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) after arrest may identify injury and aid in outcome assessments. OBJECTIVE: To analyze the association of brain lesions seen on T2-weighted MRI and diffusion-weighted imaging and N-acetylaspartate (NAA) and lactate concentrations seen on MRS with 1-year outcomes after pediatric cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study took place in pediatric intensive care units at 14 US hospitals between May 16, 2017, and August 19, 2020. Children aged 48 hours to 17 years who were resuscitated from in-hospital or out-of-hospital cardiac arrest and who had a clinical brain MRI or MRS performed within 14 days postarrest were included in the study. Data were analyzed from January 2022 to February 2023. EXPOSURE: Brain MRI or MRS. MAIN OUTCOMES AND MEASURES: The primary outcome was an unfavorable outcome (either death or survival with a Vineland Adaptive Behavior Scales, Third Edition, score of \u3c70) at 1 year after cardiac arrest. MRI brain lesions were scored according to region and severity (0 = none, 1 = mild, 2 = moderate, 3 = severe) by 2 blinded pediatric neuroradiologists. MRI Injury Score was a sum of T2-weighted and diffusion-weighted imaging lesions in gray and white matter (maximum score, 34). MRS lactate and NAA concentrations in the basal ganglia, thalamus, and occipital-parietal white and gray matter were quantified. Logistic regression was performed to determine the association of MRI and MRS features with patient outcomes. RESULTS: A total of 98 children, including 66 children who underwent brain MRI (median [IQR] age, 1.0 [0.0-3.0] years; 28 girls [42.4%]; 46 White children [69.7%]) and 32 children who underwent brain MRS (median [IQR] age, 1.0 [0.0-9.5] years; 13 girls [40.6%]; 21 White children [65.6%]) were included in the study. In the MRI group, 23 children (34.8%) had an unfavorable outcome, and in the MRS group, 12 children (37.5%) had an unfavorable outcome. MRI Injury Scores were higher among children with an unfavorable outcome (median [IQR] score, 22 [7-32]) than children with a favorable outcome (median [IQR] score, 1 [0-8]). Increased lactate and decreased NAA in all 4 regions of interest were associated with an unfavorable outcome. In a multivariable logistic regression adjusted for clinical characteristics, increased MRI Injury Score (odds ratio, 1.12; 95% CI, 1.04-1.20) was associated with an unfavorable outcome. CONCLUSIONS AND RELEVANCE: In this cohort study of children with cardiac arrest, brain features seen on MRI and MRS performed within 2 weeks after arrest were associated with 1-year outcomes, suggesting the utility of these imaging modalities to identify injury and assess outcomes

Association of blood-based brain injury biomarker concentrations with outcomes after pediatric cardiac arrest

Importance: Families and clinicians have limited validated tools available to assist in estimating long-term outcomes early after pediatric cardiac arrest. Blood-based brain-specific biomarkers may be helpful tools to aid in outcome assessment. Objective: To analyze the association of blood-based brain injury biomarker concentrations with outcomes 1 year after pediatric cardiac arrest. Design, Setting, and Participants: The Personalizing Outcomes After Child Cardiac Arrest multicenter prospective cohort study was conducted in pediatric intensive care units at 14 academic referral centers in the US between May 16, 2017, and August 19, 2020, with the primary investigators blinded to 1-year outcomes. The study included 120 children aged 48 hours to 17 years who were resuscitated after cardiac arrest, had pre-cardiac arrest Pediatric Cerebral Performance Category scores of 1 to 3 points, and were admitted to an intensive care unit after cardiac arrest. Exposure: Cardiac arrest. Main Outcomes and Measures: The primary outcome was an unfavorable outcome (death or survival with a Vineland Adaptive Behavior Scales, third edition, score of \u3c70 points) at 1 year after cardiac arrest. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCH-L1), neurofilament light (NfL), and tau concentrations were measured in blood samples from days 1 to 3 after cardiac arrest. Multivariate logistic regression and area under the receiver operating characteristic curve (AUROC) analyses were performed to examine the association of each biomarker with outcomes on days 1 to 3. Results: Among 120 children with primary outcome data available, the median (IQR) age was 1.0 (0-8.5) year; 71 children (59.2%) were male. A total of 5 children (4.2%) were Asian, 19 (15.8%) were Black, 81 (67.5%) were White, and 15 (12.5%) were of unknown race; among 110 children with data on ethnicity, 11 (10.0%) were Hispanic, and 99 (90.0%) were non-Hispanic. Overall, 70 children (58.3%) had a favorable outcome, and 50 children (41.7%) had an unfavorable outcome, including 43 deaths. On days 1 to 3 after cardiac arrest, concentrations of all 4 measured biomarkers were higher in children with an unfavorable vs a favorable outcome at 1 year. After covariate adjustment, NfL concentrations on day 1 (adjusted odds ratio [aOR], 5.91; 95% CI, 1.82-19.19), day 2 (aOR, 11.88; 95% CI, 3.82-36.92), and day 3 (aOR, 10.22; 95% CI, 3.14-33.33); UCH-L1 concentrations on day 2 (aOR, 11.27; 95% CI, 3.00-42.36) and day 3 (aOR, 7.56; 95% CI, 2.11-27.09); GFAP concentrations on day 2 (aOR, 2.31; 95% CI, 1.19-4.48) and day 3 (aOR, 2.19; 95% CI, 1.19-4.03); and tau concentrations on day 1 (aOR, 2.44; 95% CI, 1.14-5.25), day 2 (aOR, 2.28; 95% CI, 1.31-3.97), and day 3 (aOR, 2.04; 95% CI, 1.16-3.57) were associated with an unfavorable outcome. The AUROC models were significantly higher with vs without the addition of NfL on day 2 (AUROC, 0.932 [95% CI, 0.877-0.987] vs 0.871 [95% CI, 0.793-0.949]; P = .02) and day 3 (AUROC, 0.921 [95% CI, 0.857-0.986] vs 0.870 [95% CI, 0.786-0.953]; P = .03). Conclusions and Relevance: In this cohort study, blood-based brain injury biomarkers, especially NfL, were associated with an unfavorable outcome at 1 year after pediatric cardiac arrest. Additional evaluation of the accuracy of the association between biomarkers and neurodevelopmental outcomes beyond 1 year is needed

Challenges and priorities for pediatric critical care clinician-researchers in low- and middle-income countries

IntroductionThere is need for more data on critical care outcomes and interventions from low- and middle-income countries (LMIC). Global research collaborations could help improve health-care delivery for critically ill children in LMIC where child mortality rates remain high.Materials and methodsTo inform the role of collaborative research in health-care delivery for critically ill children in LMIC, an anonymous online survey of pediatric critical care (PCC) physicians from LMIC was conducted to assess priorities, major challenges, and potential solutions to PCC research. A convenience sample of 56 clinician-researchers taking care of critically ill children in LMIC was targeted. In addition, the survey was made available on a Latin American PCC website. Descriptive statistics were used for data analysis.ResultsThe majority of the 47 survey respondents worked at urban, public teaching hospitals in LMIC. Respondents stated their primary PCC research motivations were to improve clinical care and establish guidelines to standardize care. Top challenges to conducting research were lack of funding, high clinical workload, and limited research support staff. Respondent-proposed solutions to these challenges included increasing research funding options for LMIC, better access to mentors from high-income countries, research training and networks, and higher quality medical record documentation.ConclusionLMIC clinician-researchers must be better empowered and resourced to lead and influence the local and global health research agenda for critically ill children. Increased funding options, access to training and mentorship in research methodology, and improved data collection systems for LMIC PCC researchers were recognized as key needs for success

Practice patterns in pediatric infectious encephalopathy in four centers in Africa

IntroductionInfectious encephalopathy (IE), including meningitis, infectious encephalitis, and cerebral abscess, remains prevalent and carries high mortality and morbidity in children, especially in low and middle income countries (LMIC). This study aims to describe the usual care and outcomes of pediatric IE in four LMIC hospitals in sub-Saharan Africa to support evidence-based care guideline development.MethodsThis is a secondary analysis of the Prevalence of Acute Critical Neurological disease in children: A Global Epidemiological Assessment—Developing Countries study, a 4-week, prospective, observational study in children (1 week to 17 years) with IE presenting to referral hospitals in Ethiopia, Kenya, Rwanda, and Ghana. Data collection included diagnostic testing, interventions, and patient outcomes [e.g., mortality, Pediatric Cerebral and Overall Performance Category Scores (PCPC and POPC)].ResultsSeventy-two children with IE were enrolled. Most patients were diagnosed with undifferentiated IE (78%, n = 56). Specific etiologies included cerebral malaria (10%, n = 7), viral encephalitis (4%, n = 3), tuberculosis (4%, n = 3), bacterial meningitis (3%, n = 2), and cerebral abscess (1%, n = 1). Fourteen patients (20%) had a head computed tomography performed. Thirty two (44%) children had a lumbar puncture but only 9 samples (28%) were sent for culture. Median time from diagnosis to antimicrobial therapy was 3 h (IQR 1–12 h). Half (51%, n = 33) of inpatients received intracranial pressure (ICP)-directed treatment but none underwent ICP monitoring. Mortality was 13% (n = 9). The percentage of children with a favorable cognitive score decreased from 95% (n = 62) prior to admission to 80% (n = 52) and 77% (n = 50) at discharge for PCPC and POPC respectively.DiscussionIE led to considerable morbidity and mortality in this cohort, and evaluation and management varied across the care continuum. Resource limitations and diagnostic constraints may have affected diagnosis-directed therapy and other aspects of management. Further studies are needed to describe the epidemiology and management of IE in LMICs to inform future treatment protocols, the role of technological and human capacity building to support both basic monitoring and interventions, as well as creative new solutions to emergency and critical care in these settings

Post-discharge outcomes of hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C

IntroductionHospitalized children diagnosed with SARS-CoV-2-related conditions are at risk for new or persistent symptoms and functional impairments. Our objective was to analyze post-hospital symptoms, healthcare utilization, and outcomes of children previously hospitalized and diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C).MethodsProspective, multicenter electronic survey of parents of children <18 years of age surviving hospitalization from 12 U.S. centers between January 2020 and July 2021. The primary outcome was a parent report of child recovery status at the time of the survey (recovered vs. not recovered). Secondary outcomes included new or persistent symptoms, readmissions, and health-related quality of life. Multivariable backward stepwise logistic regression was performed for the association of patient, disease, laboratory, and treatment variables with recovered status.ResultsThe children [n = 79; 30 (38.0%) female] with acute SARS-CoV-2 (75.7%) or MIS-C (24.3%) had a median age of 6.5 years (interquartile range 2.0–13.0) and 51 (64.6%) had a preexisting condition. Fifty children (63.3%) required critical care. One-third [23/79 (29.1%)] were not recovered at follow-up [43 (31, 54) months post-discharge]. Admission C-reactive protein levels were higher in children not recovered vs. recovered [5.7 (1.3, 25.1) vs. 1.3 (0.4, 6.3) mg/dl, p = 0.02]. At follow-up, 67% overall had new or persistent symptoms. The most common symptoms were fatigue (37%), weakness (25%), and headache (24%), all with frequencies higher in children not recovered. Forty percent had at least one return emergency visit and 24% had a hospital readmission. Recovered status was associated with better total HRQOL [87 (77, 95) vs. 77 (51, 83), p = 0.01]. In multivariable analysis, lower admission C-reactive protein [odds ratio 0.90 (95% confidence interval 0.82, 0.99)] and higher admission lymphocyte count [1.001 (1.0002, 1.002)] were associated with recovered status.ConclusionsChildren considered recovered by their parents following hospitalization with SARS-CoV-2-related conditions had less symptom frequency and better HRQOL than those reported as not recovered. Increased inflammation and lower lymphocyte count on hospital admission may help to identify children needing longitudinal, multidisciplinary care.Clinical Trial RegistrationClinicalTrials.gov (NCT04379089)

P-COSCA (Pediatric Core Outcome Set for Cardiac Arrest) in children : an advisory statement from the International Liaison Committee on Resuscitation

Studies of pediatric cardiac arrest use inconsistent outcomes, including return of spontaneous circulation and short-term survival, and basic assessments of functional and neurological status. In 2018, the International Liaison Committee on Resuscitation sponsored the COSCA initiative (Core Outcome Set After Cardiac Arrest) to improve consistency in reported outcomes of clinical trials of adult cardiac arrest survivors and supported this P-COSCA initiative (pediatric COSCA). The P-COSCA Steering Committee generated a list of potential survival, life impact, and economic impact outcomes and assessment time points that were prioritized by a multidisciplinary group of healthcare providers, researchers, and parents/caregivers of children who survived cardiac arrest. Then, expert panel discussions achieved consensus regarding the core outcomes, the methods to measure those core outcomes, and the timing of the measurements. The P-COSCA includes assessment of survival, brain function, cognitive function, physical function, and basic daily life skills. Survival and brain function were assessed at discharge or 30 days (or both if possible) and between 6 and 12 months postarrest. Cognitive function, physical function, and basic daily life skills were assessed between 6 and 12 months after cardiac arrest. Because many children have prearrest comorbidities, the P-COSCA also includes documentation of baseline (ie, prearrest) brain function and calculation of changes after cardiac arrest. Supplementary outcomes of survival, brain function, cognitive function, physical function, and basic daily life skills are assessed at 3 months and beyond 1 year after cardiac arrest if resources are available

Brief Report: Incidence and Outcomes of Pediatric Tracheal Intubation-Associated Cardiac Arrests in the ICU-RESUS Clinical Trial

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)

A Core Outcome Set for Pediatric Critical Care

Objectives: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs.Design: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% “critical” and less than 15% “not important” advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components.Setting: Multinational survey.Patients: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates.Measurements and Main Results: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% “critical” and less than 15% “not important” and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set—extended.Conclusions: The PICU core outcome set and PICU core outcome set—extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families

Early Bolus Epinephrine Administration During Pediatric Cardiopulmonary Resuscitation for Bradycardia with Poor Perfusion: An ICU-Resuscitation Study

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 (\u3c 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 \u3c 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