Associations Between End-Tidal Carbon Dioxide During Pediatric Cardiopulmonary Resuscitation, Cardiopulmonary Resuscitation Quality, and Survival.

BACKGROUND: Supported by laboratory and clinical investigations of adult cardiopulmonary arrest, resuscitation guidelines recommend monitoring end-tidal carbon dioxide (ETCO2) as an indicator of cardiopulmonary resuscitation (CPR) quality, but they note that "specific values to guide therapy have not been established in children." METHODS: This prospective observational cohort study was a National Heart, Lung, and Blood Institute-funded ancillary study of children in the ICU-RESUS trial (Intensive Care Unit-Resuscitation Project; NCT02837497). Hospitalized children (≤18 years of age and ≥37 weeks postgestational age) who received chest compressions of any duration for cardiopulmonary arrest, had an endotracheal or tracheostomy tube at the start of CPR, and evaluable intra-arrest ETCO2 data were included. The primary exposure was event-level average ETCO2 during the first 10 minutes of CPR (dichotomized as ≥20 mm Hg versus <20 mm Hg on the basis of adult literature). The primary outcome was survival to hospital discharge. Secondary outcomes were sustained return of spontaneous circulation, survival to discharge with favorable neurological outcome, and new morbidity among survivors. Poisson regression measured associations between ETCO2 and outcomes as well as the association between ETCO2 and other CPR characteristics: (1) invasively measured systolic and diastolic blood pressures, and (2) CPR quality and chest compression mechanics metrics (ie, time to CPR start; chest compression rate, depth, and fraction; ventilation rate). RESULTS: Among 234 included patients, 133 (57%) had an event-level average ETCO2 ≥20 mm Hg. After controlling for a priori covariates, average ETCO2 ≥20 mm Hg was associated with a higher incidence of survival to hospital discharge (86/133 [65%] versus 48/101 [48%]; adjusted relative risk, 1.33 [95% CI, 1.04-1.69]; P=0.023) and return of spontaneous circulation (95/133 [71%] versus 59/101 [58%]; adjusted relative risk, 1.22 [95% CI, 1.00-1.49]; P=0.046) compared with lower values. ETCO2 ≥20 mm Hg was not associated with survival with favorable neurological outcome or new morbidity among survivors. Average 2 ≥20 mm Hg was associated with higher systolic and diastolic blood pressures during CPR, lower CPR ventilation rates, and briefer pre-CPR arrest durations compared with lower values. Chest compression rate, depth, and fraction did not differ between ETCO2 groups. CONCLUSIONS: In this multicenter study of children with in-hospital cardiopulmonary arrest, ETCO2 ≥20 mm Hg was associated with better outcomes and higher intra-arrest blood pressures, but not with chest compression quality metrics.

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.

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.

Ablation Rates and Long-Term Outcome Following Low-Dose Radioiodine for Differentiated Thyroid Cancer in the West of Scotland: A Retrospective Analysis.

OBJECTIVE: Low-dose radioiodine is an accepted means of remnant ablation in patients with low- to intermediate-risk differentiated thyroid cancer (DTC) based on the results of several phase III trials. We evaluated the rate of ablation success and long-term recurrence outcomes in the first 3 years of implementing this practice at our institution. METHODS: Patients who received 1.1 to 1.2 gigabecquerel (30 millicurie) were identified retrospectively from the radionuclide database, January 1, 2012, to December 31, 2014, inclusive. Successful ablation was defined as Iodine-131uptake <0.1% on diagnostic scan and Tg level <2.0 ng/mL at 6 to 8 months after treatment. Follow-up was conducted annually for 10 years and relapse rates were determined based on the available clinical, radiological, and biochemical information. RESULTS: We identified 114 patients, 109 of whom had dual response assessment. The median age was 43 years (range, 14 to 80 years). Almost 70% had T1 or T2 tumors, with T3 and T4 tumors recorded in 27% and 2.5% of patients, respectively. Nodal staging was performed in just over 30% and involved lymph nodes were detected in 21% (N1a 8% and N1b 13%). Ablation success based on diagnostic scan alone was 94.7% (108/114), Tg alone 94.7% (108/114), and on both modalities was 90.4% (103/114). CONCLUSION: Remnant ablation was achieved in >90%, and the corresponding clinical recurrence rate was only 1.8% despite the inclusion of patients with locally advanced disease. Low-dose radioiodine is effective and may be suitable for a proportion of patients with higher-risk DTC.

Survival With Favorable Neurologic Outcome and Quality of Cardiopulmonary Resuscitation Following In-Hospital Cardiac Arrest in Children With Cardiac Disease Compared With Noncardiac Disease.

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.

Early Cardiac Arrest Hemodynamics, End-Tidal C o2 , and Outcome in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021).

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.

Diastolic Blood Pressure Threshold During Pediatric Cardiopulmonary Resuscitation and Survival Outcomes: A Multicenter Validation Study.

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.

The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes.

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

Identification of post-cardiac arrest blood pressure thresholds associated with outcomes in children: an ICU-Resuscitation study.

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.

The relationship between fathers' heavy episodic drinking and fathering involvement in five Asia-Pacific countries: An individual participant data meta-analysis.

BACKGROUND: This study aims to increase understanding of the relationship between heavy episodic drinking (HED) and fathers' involvement in parenting in five countries. The potential moderating effect of fathers' experiences of childhood trauma is also studied, controlling for the possible confounding of the effect of HED by father's attitudes toward gender equality, father's age and father's education. METHOD: United Nations Multi-Country Study on Men and Violence (UNMCS) survey data from 4562 fathers aged 18-49 years from Cambodia, China, Indonesia and Papua New Guinea (PNG) and Sri Lanka were used to assess the relationship between fathering involvement (e.g., helping children with their homework) and self-reported HED of 6+ drinks in one occasion vs. non-HED and abstaining. Moderating effects of a 13-item fathers' childhood trauma (FCT) scale were tested and analyses were adjusted for gender-inequitable attitudes using the Gender-Equitable Men scale score. Bivariate and adjusted individual participant meta-analyses were used to determine effect estimates for each site and across all sites. RESULTS: Fathers' HED was associated with less positive parental involvement after adjusting for gender-equitable attitudes, FCT, age and education. No overall interaction between HED and FCT was identified. Gender equitable attitudes were associated with fathering involvement in some countries but not overall (p = 0.07). CONCLUSIONS: Heavy episodic drinking was associated with reduced positive fathering involvement. These findings suggest that interventions to increase fathers' involvement in parenting should include targeting reductions in fathers' HED. Structural barriers to fathers' involvement should be considered alongside HED in future studies of fathers' engagement with their children.

Sodium Bicarbonate Use During Pediatric Cardiopulmonary Resuscitation: A Secondary Analysis of the ICU-RESUScitation Project Trial.

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.

The Effect of Epinephrine Dosing Intervals on Outcomes from Pediatric In-Hospital Cardiac Arrest.

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

Effect of Physiologic Point-of-Care Cardiopulmonary Resuscitation Training on Survival With Favorable Neurologic Outcome in Cardiac Arrest in Pediatric ICUs: A Randomized Clinical Trial.

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.

Noticed and then Forgotten: Gender in Alcohol Policy Stakeholder Responses to Alcohol and Violence.

In this article, we analyse interview data on how alcohol policy stakeholders in Australia, Canada and Sweden understand the relationship between men, masculinities, alcohol and violence. Using influential feminist scholarship on public policy and liberal political theory to analyse interviews with 42 alcohol policy stakeholders, we argue that while these stakeholders view men's violence as a key issue for intervention, masculinities are backgrounded in proposed responses and men positioned as unamenable to intervention. Instead, policy stakeholders prioritise generic interventions understood to protect all from the harms of men's drinking and violence without marking men for special attention. Shared across the data is a prioritisation of interventions that focus on harms recognised as relating to men's drinking but apply equally to all people and, as such, avoid naming men and masculinities as central to alcohol-related violence. We argue that this process works to background the role of masculinities in violence, leaving men unmarked and many possible targeted responses unthinkable.

A gender-focused multilevel analysis of how country, regional and individual level factors relate to harm from others' drinking.

BACKGROUND: The aim of this study was to examine how gender, age and education, regional prevalence of male and female risky drinking and country-level economic gender equality are associated with harms from other people's drinking. METHODS: 24,823 adults in ten countries were surveyed about harms from drinking by people they know and strangers. Country-level economic gender equality and regional prevalence of risky drinking along with age and gender were entered as independent variables into three-level random intercept models predicting alcohol-related harm. FINDINGS: At the individual level, younger respondents were consistently more likely to report harms from others' drinking, while, for women, higher education was associated with lower risk of harms from known drinkers but higher risk of harms from strangers. Regional rate of men's risky drinking was associated with known and stranger harm, while regional-level women's risky drinking was associated with harm from strangers. Gender equality was only associated with harms in models in models that did not include risky drinking. CONCLUSIONS: Youth and regional levels of men's drinking was consistently associated with harm from others attributable to alcohol. Policies that decrease the risky drinking of men would be likely to reduce harms attributable to the drinking of others.

Defining Clinical Public Health.

PURPOSE: To solve complex health issues, an innovative and multidisciplinary framework is necessary. The Clinical Public Health (CPH) Division was established at the University of Toronto (UofT), Canada to foster inte-gration of primary care, preventive medicine and public health in education, practice and research. To better understand how the construct of CPH might be applied, we surveyed clinicians, researchers and public health professionals affiliated with the CPH Division to assess their understanding of the CPH concept and its utility in fostering broad collaboration. METHODS: A two-wave anonymous survey of the active faculty of the CPH Division, UofT was conducted across Canada. Wave 1 participants (n = 187; 2016) were asked to define CPH, while Wave 2 participants (n = 192; 2017) were provided a synthesis of Wave 1 results and asked to rank each definition. Both waves were asked about the need for a common definition, and to comment on CPH. RESULTS: Response rates for the first and second waves were 25% and 22%, respectively. Of the six definitions of CPH from Wave 1, "the intersection of clinical practice and public health," was most highly ranked by Wave 2 participants. Positive perceptions of CPH included multidisciplinary collaboration, new fields and insights, forward thinking and innovation. Negative perceptions included CPH being a confusing term, too narrow in scope or too clinical. CONCLUSION: The concept of Clinical Public Health can foster multidisciplinary collaboration to address com-plex health issues because it provides a useful framework for bringing together key disciplines and diverse professional specialties.

Systemic Endothelial Activation Is Associated With Early Acute Respiratory Distress Syndrome in Children With Extrapulmonary Sepsis.

OBJECTIVES: Systemic endothelial activation may contribute to sepsis-associated organ injury, including acute respiratory distress syndrome. We hypothesized that children with extrapulmonary sepsis with versus without acute respiratory distress syndrome would have plasma biomarkers indicative of increased endothelial activation and that persistent biomarker changes would be associated with poor outcome. DESIGN: Observational cohort. SETTING: Academic PICU. PATIENTS: Patients less than 18 years old with sepsis from extrapulmonary infection with (n = 46) or without (n = 54) acute respiratory distress syndrome and noninfected controls (n = 19). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endothelial (angiopoietin-1, angiopoietin-2, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin) and inflammatory biomarkers (C-reactive protein, interleukin-6, and interleukin-8) were measured from peripheral plasma collected within 3 days (time 1) of sepsis recognition and at 3-6 days (time 2) and 7-14 days (time 3). Time 1 biomarkers and longitudinal measurements were compared for sepsis patients with versus without acute respiratory distress syndrome and in relation to complicated course, defined as greater than or equal to two organ dysfunctions at day 7 or death by day 28. Angiopoietin-2, angiopoietin-2/angiopoietin-1 ratio, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin, endocan, C-reactive protein, interleukin-6, and interleukin-8 were different between sepsis and noninfected control patients at time 1. Among patients with sepsis, those with acute respiratory distress syndrome had higher angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor, vascular cell adhesion molecule, thrombomodulin, endocan, interleukin-6, and interleukin-8 than those without acute respiratory distress syndrome (all p < 0.003). Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio remained higher in sepsis with versus without acute respiratory distress syndrome after multivariable analyses. Time 1 measures of angiopoietin-2, angiopoietin-2/-1 ratio, von Willebrand factor, and endocan were indicative of complicated course in all sepsis patients (all area under the receiver operating curve ≥ 0.80). In sepsis without acute respiratory distress syndrome, soluble fms-like tyrosine kinase decreased more quickly and von Willebrand factor and thrombomodulin decreased more slowly in those with complicated course. CONCLUSIONS: Children with extrapulmonary sepsis with acute respiratory distress syndrome had plasma biomarkers indicative of greater systemic endothelial activation than those without acute respiratory distress syndrome. Several endothelial biomarkers measured near sepsis recognition were associated with complicated course, whereas longitudinal biomarker changes yielded prognostic information only in those without sepsis-associated acute respiratory distress syndrome.

Survival and Hemodynamics During Pediatric Cardiopulmonary Resuscitation for Bradycardia and Poor Perfusion Versus Pulseless Cardiac Arrest.

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

Circulating Neurofilament Light Chain Is Associated With Survival After Pediatric Cardiac Arrest.

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