Resuscitation arterial waveform quantification and outcomes in pediatric bidirectional Glenn and Fontan patients.

BACKGROUND: Resuscitation with chest compressions and positive pressure ventilation in Bidirectional Glenn (BDG) or Fontan physiology may compromise passive venous return and accentuate neurologic injury. We hypothesized that arterial pressure and survival would be better in BDG than Fontan patients. METHODS: Secondary analyses of the Pediatric Intensive Care Quality of CPR and Improving Outcomes from Pediatric Cardiac Arrest databases. P-values were considered significant if < 0.05. RESULTS: In total, 64 patients had either BDG (42/64, 66%) or Fontan (22/64, 34%) anatomy. Return of spontaneous circulation was achieved in 76% of BDG patients versus 59% of Fontan patients and survival with favorable neurologic outcome in 22/42 (52%) BDG versus 6/22 (27%) Fontan patients, p = 0.067. Twelve of 24 (50%) BDG and 2/7 (29%) Fontan patients who survived to discharge suffered new morbidity as defined by worsening Functional Status Score. More BDG patients achieved adequate DBP (≥25 mmHg for neonates and infants; ≥ 30 mmHg for children) than Fontan patients (21/23 (91%) vs. 5/11 (46%), p = 0.007). CONCLUSIONS: Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after CPR, likely driven by inadequate diastolic blood pressure during resuscitation. One half of the BDG patients who survived to hospital discharge had new neurologic morbidity. BACKGROUND: Cardiac arrest in patients with congenital heart disease (CHD) may present challenges to resuscitation based on the unique cardiovascular physiology resulting from surgical palliation. Recent resuscitation guidelines for CHD patients highlight the lack of data surrounding these special patient populations.1 Univentricular heart disease is palliated by a series of cardiac surgeries that stepwise result in passive pulmonary perfusion from the systemic venous system directly to the pulmonary vascular bed. The bidirectional Glenn (BDG) palliation directly anastomoses the superior vena cava (SVC) to the pulmonary arterial system and leaves normal inferior vena cava (IVC) venous return to the heart.2 The Fontan palliation baffles IVC flow directly to the pulmonary vascular bed which relieves cyanosis due to right to left shunting, but requires systemic ventricular preload to be directly dependent upon pulmonary vascular resistance and intrathoracic pressures.3 IMPACT STATEMENT: Hemodynamic waveforms from 2 large prospective observational studies now allow for exploration of physiology during cardiopulmonary resuscitation for unique anatomy associated with single ventricle congenital heart disease. Fewer patients with Fontan physiology (46%) achieved an adequate diastolic blood pressure (defined as ≥ 25 mmHg for neonates and infants and ≥ 30 mmHg for children) than bidirectional Glenn patients during cardiopulmonary resuscitation (91%, p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after cardiopulmonary resuscitation. Of the bidirectional Glenn patients who survived, 50% developed a new morbidity as quantified by the Functional Status Score.

Cardiopulmonary resuscitation employing only abdominal compressions in infants after cardiac surgery: A secondary sub-analysis of the ICU-RESUS study.

Importance: Patients with underlying cardiac disease form a considerable proportion of pediatric patients who experience in-hospital cardiac arrest. In pediatric patients after cardiac surgery, CPR with abdominal compressions alone (AC-CPR) may provide an alternative to standard chest compression CPR (S-CPR) with additional procedural and physiologic advantages. Objective: Quantitatively describe hemodynamics during cardiopulmonary resuscitation (CPR) and outcomes of infants who received only abdominal compressions (AC-CPR). Design: This is a sub-group analysis of the prospective, observational cohort from the ICU-RESUS trial NCT028374497. Setting & Patients: A single site quaternary care pediatric cardiothoracic intensive care unit enrolled in the ICU-RESUS trial. Patients less than 1 year of age with congenital heart disease who required compressions during cardiac arrest. Interventions: Use of AC-CPR during cardiac arrest resuscitation. Measurements and Main Results: Invasive arterial line waveforms during CPR were analyzed for 11 patients (10 surgical cardiac and 1 medical cardiac). Median weight was 3.3 kg [IQR 3.0, 4.0]; and median duration of CPR was 5.0 [3.0, 20.0] minutes. Systolic (median 57 [IQR 48, 65] mmHg) and diastolic (median 32 [IQR 24, 43] mmHg) blood pressures were achieved with a median rate of 114 [IQR 100, 124] compressions per minute. Return of spontaneous circulation was obtained in 9 of 11 (82%) patients; 2 patients (18%) were cannulated for extracorporeal cardiopulmonary resuscitation (ECPR) and 6 (55%) survived to hospital discharge with favorable neurologic outcome. Conclusions: AC-CPR may offer an alternative method to maintain perfusion for infants who experience cardiac arrest. This may have particular benefit in pediatric patients after cardiac surgery for whom external chest compressions may be harmful due to anatomic and physiologic considerations.

Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model.

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

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).

Characteristics of Pediatric In-Hospital Cardiac Arrests and Resuscitation Duration.

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

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 (< 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.

Association of Postarrest Hypotension Burden With Unfavorable Neurologic Outcome After Pediatric Cardiac Arrest.

OBJECTIVE: Quantify hypotension burden using high-resolution continuous arterial blood pressure (ABP) data and determine its association with outcome after pediatric cardiac arrest. DESIGN: Retrospective observational study. SETTING: Academic PICU. PATIENTS: Children 18 years old or younger admitted with in-of-hospital or out-of-hospital cardiac arrest who had invasive ABP monitoring during postcardiac arrest care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: High-resolution continuous ABP was analyzed up to 24 hours after the return of circulation (ROC). Hypotension burden was the time-normalized integral area between mean arterial pressure (MAP) and fifth percentile MAP for age. The primary outcome was unfavorable neurologic status (pediatric cerebral performance category ≥ 3 with change from baseline) at hospital discharge. Mann-Whitney U tests compared hypotension burden, duration, and magnitude between favorable and unfavorable patients. Multivariable logistic regression determined the association of unfavorable outcomes with hypotension burden, duration, and magnitude at various percentile thresholds from the 5th through 50th percentile for age. Of 140 patients (median age 53 [interquartile range 11-146] mo, 61% male); 63% had unfavorable outcomes. Monitoring duration was 21 (7-24) hours. Using a MAP threshold at the fifth percentile for age, the median hypotension burden was 0.01 (0-0.11) mm Hg-hours per hour, greater for patients with unfavorable compared with favorable outcomes (0 [0-0.02] vs. 0.02 [0-0.27] mm Hg-hr per hour, p < 0.001). Hypotension duration and magnitude were greater for unfavorable compared with favorable patients (0.03 [0-0.77] vs. 0.71 [0-5.01]%, p = 0.003; and 0.16 [0-1.99] vs. 2 [0-4.02] mm Hg, p = 0.001). On logistic regression, a 1-point increase in hypotension burden below the fifth percentile for age (equivalent to 1 mm Hg-hr of burden per hour of recording) was associated with increased odds of unfavorable outcome (adjusted odds ratio [aOR] 14.8; 95% CI, 1.1-200; p = 0.040). At MAP thresholds of 10th-50th percentiles for age, MAP burden below the threshold was greater in unfavorable compared with favorable patients in a dose-dependent manner. CONCLUSIONS: High-resolution continuous ABP data can be used to quantify hypotension burden after pediatric cardiac arrest. The burden, duration, and magnitude of hypotension are associated with unfavorable neurologic outcomes.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

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.

Association of EEG characteristics with outcomes following pediatric ICU cardiac arrest: A secondary analysis of the ICU-RESUScitation trial.

BACKGROUND AND OBJECTIVES: There are limited tools available following cardiac arrest to prognosticate neurologic outcomes. Prior retrospective and single center studies have demonstrated early EEG features are associated with neurologic outcome. This study aimed to evaluate the prognostic value of EEG for pediatric in-hospital cardiac arrest (IHCA) in a prospective, multicenter study. METHODS: This cohort study is a secondary analysis of the ICU-Resuscitation trial, a multicenter randomized interventional trial conducted at 18 pediatric and pediatric cardiac ICUs in the United States. Patients who achieved return of circulation (ROC) and had post-ROC EEG monitoring were eligible for inclusion. Patients < 90 days old and those with pre-arrest Pediatric Cerebral Performance Category (PCPC) scores > 3 were excluded. EEG features of interest included EEG Background Category, and presence of focal abnormalities, sleep spindles, variability, reactivity, periodic and rhythmic patterns, and seizures. The primary outcome was survival to hospital discharge with favorable neurologic outcome. Associations between EEG features and outcomes were assessed with multivariable logistic regression. Prediction models with and without EEG Background Category were developed and receiver operator characteristic curves compared. RESULTS: Of the 1129 patients with an index cardiac arrest who achieved ROC in the parent study, 261 had EEG within 24 h of ROC, of which 151 were evaluable. The cohort included 57% males with a median age of 1.1 years (IQR 0.4, 6.8). EEG features including EEG Background Category, sleep spindles, variability, and reactivity were associated with survival with favorable outcome and survival, (all p < 0.001). The addition of EEG Background Category to clinical models including age category, illness category, PRISM score, duration of CPR, first documented rhythm, highest early post-arrest arterial lactate improved the prediction accuracy achieving an AUROC of 0.84 (CI 0.77-0.92), compared to AUROC of 0.76 (CI 0.67-0.85) (p = 0.005) without EEG Background Category. CONCLUSION: This multicenter study demonstrates the value of EEG, in the first 24 h following ROC, for predicting survival with favorable outcome after a pediatric IHCA.

Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest.

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

Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024.

Background: This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk. Methods: This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership. Results: Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles. Conclusions: Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD.

Noninvasive Positive Pressure Ventilation Use and In-Hospital Cardiac Arrest in Bronchiolitis.

IMPORTANCE: A recent study showed an association between high hospital-level noninvasive positive pressure ventilation (NIPPV) use and in-hospital cardiac arrest (IHCA) in children with bronchiolitis. OBJECTIVES: We aimed to determine if patient-level exposure to NIPPV in children with bronchiolitis was associated with IHCA. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study at a single-center quaternary PICU in North America including children with International Classification of Diseases primary or secondary diagnoses of bronchiolitis in the Virtual Pediatric Systems database. MAIN OUTCOMES AND MEASURES: The primary exposure was NIPPV and the primary outcome was IHCA. MEASUREMENTS AND MAIN RESULTS: Of 4698 eligible ICU admissions with bronchiolitis diagnoses, IHCA occurred in 1.2% (57/4698). At IHCA onset, invasive mechanical ventilation (IMV) was the most frequent level of respiratory support (65%, 37/57), with 12% (7/57) receiving NIPPV. Patients with IHCA had higher Pediatric Risk of Mortality-III scores (3 [0-8] vs. 0 [0-2]; p < 0.001), more frequently had a complex chronic condition (94.7% vs. 46.2%; p < 0.001), and had higher mortality (21.1% vs. 1.0%; p < 0.001) compared with patients without IHCA. Return of spontaneous circulation (ROSC) was achieved in 93% (53/57) of IHCAs; 79% (45/57) survived to hospital discharge. All seven children without chronic medical conditions and with active bronchiolitis symptoms at the time of IHCA achieved ROSC, and 86% (6/7) survived to discharge. In multivariable analysis restricted to patients receiving NIPPV or IMV, NIPPV exposure was associated with lower odds of IHCA (adjusted odds ratio [aOR], 0.07; 95% CI, 0.03-0.18) compared with IMV. In secondary analysis evaluating categorical respiratory support in all patients, compared with IMV, NIPPV was associated with lower odds of IHCA (aOR, 0.35; 95% CI, 0.14-0.87), whereas no difference was found for minimal respiratory support (none/nasal cannula/humidified high-flow nasal cannula [aOR, 0.56; 95% CI, 0.23-1.36]). CONCLUSIONS AND RELEVANCE: Cardiac arrest in children with bronchiolitis is uncommon, occurring in 1.2% of bronchiolitis ICU admissions. NIPPV use in children with bronchiolitis was associated with lower odds of IHCA.

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Prognostic and morphological factors in pediatric cerebellar contusions.

Background: Although uncommon, cerebellar contusions are associated with significant morbidity and mortality. Literature is lacking in the prognostic and morphological factors relating to their clinical picture and outcomes, especially within children. The objective of this study is to evaluate prognostic and anatomic factors in the clinical picture of cerebellar contusions, including effacement of the 4th ventricle and cisterna magna. Methods: This is a retrospective chart review over 11 years across two medical centers. Patients included were under 18 years who presented with a cerebellar contusion. Patients were stratified within the study group based on discharge Glasgow outcome scale (GOS) and reviewed for prognostic factors contributing to outcome. Mid sagittal area of the 4th ventricle and cisterna magna were measured using magnetic resonance imaging and compared within the groups. Results: A total of 21 patients met the study criteria, of which 16 (76.2%) were male, with an average patient age of 8.65 years. Poor outcome at discharge (GOS <4) was associated with decreased admission Glasgow coma scale (P = 0.003), admission motor response (P = 0.006), pupil reactivity (P = 0.014), presence of concomitant subarachnoid hemorrhage (P = 0.010), contusion volume (P < 0.001), and decreased area of the cisterna magna (P = 0.012). Patients with poor outcomes were also more likely to require surgical intervention (P = 0.042). Conclusion: There are multiple prognostic factors associated with the overall outcome following cerebellar contusions. The rate of good outcomes in this study was superior to that in previous studies in adults.

Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024.

BACKGROUND: This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk. METHODS: This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership. RESULTS: Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles. CONCLUSIONS: Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD.

Association Between Chest Compression Pause Duration and Survival After Pediatric In-Hospital Cardiac Arrest.

BACKGROUND: The association between chest compression (CC) pause duration and pediatric in-hospital cardiac arrest survival outcomes is unknown. The American Heart Association has recommended minimizing pauses in CC in children to <10 seconds, without supportive evidence. We hypothesized that longer maximum CC pause durations are associated with worse survival and neurological outcomes. METHODS: In this cohort study of index pediatric in-hospital cardiac arrests reported in pediRES-Q (Quality of Pediatric Resuscitation in a Multicenter Collaborative) from July of 2015 through December of 2021, we analyzed the association in 5-second increments of the longest CC pause duration for each event with survival and favorable neurological outcome (Pediatric Cerebral Performance Category ≤3 or no change from baseline). Secondary exposures included having any pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds per 2 minutes. RESULTS: We identified 562 index in-hospital cardiac arrests (median [Q1, Q3] age 2.9 years [0.6, 10.0], 43% female, 13% shockable rhythm). Median length of the longest CC pause for each event was 29.8 seconds (11.5, 63.1). After adjustment for confounders, each 5-second increment in the longest CC pause duration was associated with a 3% lower relative risk of survival with favorable neurological outcome (adjusted risk ratio, 0.97 [95% CI, 0.95-0.99]; P=0.02). Longest CC pause duration was also associated with survival to hospital discharge (adjusted risk ratio, 0.98 [95% CI, 0.96-0.99]; P=0.01) and return of spontaneous circulation (adjusted risk ratio, 0.93 [95% CI, 0.91-0.94]; P<0.001). Secondary outcomes of any pause >10 seconds or >20 seconds and number of CC pauses >10 seconds and >20 seconds were each significantly associated with adjusted risk ratio of return of spontaneous circulation, but not survival or neurological outcomes. CONCLUSIONS: Each 5-second increment in longest CC pause duration during pediatric in-hospital cardiac arrest was associated with lower chance of survival with favorable neurological outcome, survival to hospital discharge, and return of spontaneous circulation. Any CC pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds were significantly associated with lower adjusted probability of return of spontaneous circulation, but not survival or neurological outcomes.

Wolf Creek XVII Part 6: Physiology-Guided CPR.

Introduction: Physiology-guided cardiopulmonary resuscitation (CPR) offers the potential to optimize resuscitation and enable early prognosis. Methods: Physiology-Guided CPR was one of six focus topic for the Wolf Creek XVII Conference held on June 14-17, 2023 in Ann Arbor, Michigan, USA. International thought leaders and scientists in the field of cardiac arrest resuscitation from academia and industry were invited. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category, which was then debated, revised and ranked by all attendees to identify the top 5 for each category. Results: Top knowledge gaps include identifying optimal strategies for the evaluation of physiology-guided CPR and the optimal values for existing patients using patient outcomes. The main barriers to translation are the limited usability outside of critical care environments and the training and equipment required for monitoring. The top research priorities are the development of clinically feasible and reliable methods to continuously and non-invasively monitor physiology during CPR and prospective human studies proving targeting parameters during CPR improves outcomes. Conclusion: Physiology-guided CPR has the potential to provide individualized resuscitation and move away from a one-size-fits-all approach. Current understanding is limited, and clinical trials are lacking. Future developments need to consider the clinical application and applicability of measurement to all healthcare settings. Therefore, clinical trials using physiology-guided CPR for individualisation of resuscitation efforts are needed.

Association of Pediatric Postcardiac Arrest Ventilation and Oxygenation with Survival Outcomes.

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 (PaO2) <60 mm Hg, highest PaO2 ⩾200 mm Hg, or every PaO2 60-199 mm Hg, respectively-and hypocapnia, hypercapnia, or normocapnia, defined as lowest arterial carbon dioxide tension/pressure (PaCO2) <30 mm Hg, highest PaCO2 ⩾50 mm Hg, or every PaCO2 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.

Müllerian-type carcinosarcoma arising in gastric endometriosis: Case report and review of the literature.

Although endometriosis is a common condition, both extrapelvic endometriosis and endometriosis associated malignancy (EAM) are rare. We describe the first reported case of a patient with Müllerian-type carcinosarcoma arising in gastric endometriosis.