Robert Michael Sutton

Objectives: To develop and internally validate a multivariable prediction model for survival to hospital discharge after pediatric extracorporeal cardiopulmonary resuscitation (ECPR) for in-hospital cardiac arrest (IHCA), and to use this model to derive risk-standardized survival rates (RSSRs) and quantify between-hospital variation in outcomes. Design: Retrospective multicenter cohort study. Setting: Hospitals contributing to the Extracorporeal Life Support Organization (ELSO) registry between 2020 and 2023. Patients: Children (< 18 yr) treated with ECPR for IHCA. Interventions: None. Measurements and Main Results: Eligible patients were identified from the ELSO Registry and split into derivation ( N = 1060) and validation ( N = 317) cohorts using a hospital-stratified split to preserve within-hospital clustering. Survival prediction models were derived using penalized logistic regression with the least absolute shrinkage and selection operator. A full-event model incorporating 14 routinely available clinical variables demonstrated fair discrimination (area under the curve, 0.728 in the derivation cohort and 0.678 in the validation cohort) and good calibration (observed-to-expected ratio, 0.995; Brier score, 0.222 in the validation cohort). This model was embedded in a multilevel logistic regression model to generate hospital-level RSSRs for centers reporting five or more ECPR cases. Between-hospital variation was quantified using the median odds ratio, which was 1.30 (95% CI, 1.11–1.93), indicating significant differences in survival likelihood between centers after adjusting for patient-level risk. Conclusions: In a large, international cohort of pediatric ECPR patients, we developed and internally validated a clinically interpretable model for survival to hospital discharge. The model performance as a discriminator likely limits its use as a standalone tool for clinical decision-making. However, strong internal calibration allowed for determination of hospital-level RSSRs, which revealed significant inter-hospital variability. These findings demonstrate the feasibility of developing a risk-adjustment model capable of estimating hospital-level RSSRs. Additional external validation and evaluation of residual case-mix differences are needed before such models can be used for benchmarking across pediatric ECPR centers.

Objectives: Evaluate the association between cardiopulmonary resuscitation (CPR) ventilation rates and survival to hospital discharge, and identify novel ventilation targets. Design: Multicenter prospective ancillary observational cohort study of the ICU-RESUS trial (NCT02837497). Setting: A total of 18 ICUs from 10 U.S. clinical sites from October 2016 to March 2021. Patients: Hospitalized children (≤ 18 yr) with endotracheal or tracheostomy tubes and evaluable intra-arrest end-tidal carbon dioxide data to calculate ventilation rate. Interventions: None. Measurements and Main Results: Among 234 included events, 86 events (36.8%) had guideline-recommended (20–30 beats per min [bpm]) average ventilation rates during CPR. The association between guideline-recommended CPR ventilation rate and survival to hospital discharge was evaluated with Poisson regression using generalized estimating equations, controlling for a priori covariables (initial pulse status, immediate cause of arrest). We found no association between guideline-recommended ventilation rates and survival to hospital discharge (adjusted relative risk [aRR], 0.95; 95% CI, 0.75–1.21; p = 0.68). In exploratory analyses, novel age-stratified ventilation rates were identified using natural cubic splines and subsequently evaluated in multivariable models. We identified potential thresholds (< 8 yr, ≥ 26 bpm; ≥ 8 yr, < 26 bpm). For children younger than 8 years, average CPR ventilation rate greater than or equal to 26 bpm was associated with improved survival to hospital discharge compared with less than 26 bpm (aRR, 1.32; 95% CI, 1.00–1.73; p = 0.048). Conclusions: CPR ventilation rates in the currently recommended range (20–30 bpm) were not associated with survival in children with in-hospital cardiac arrest. In exploratory analyses in children younger than 8 years, higher ventilation rates (≥ 26 bpm) were associated with improved survival and warrant confirmation in future studies.

BACKGROUND: High-quality cardiopulmonary resuscitation is associated with improved outcomes; however, specific targets for younger age groups are largely based on extrapolations from adult studies and small pediatric cohort studies. METHODS: Prospectively designed embedded study within the ICU RESUScitation Project (ICU-RESUS). Children (≤18 years) who received cardiopulmonary resuscitation in 10 intensive care units in the United States were enrolled between 2016 and 2021. We excluded patients with documented limitations of care, who were brain dead, or who had OHCA. The exposures were American Heart Association-recommended chest compression (CC) targets for rate (100–120 cm ³ /min), depth (≥40 mm for age 80%). Associations between achieving CC targets over the first 10 minutes of cardiopulmonary resuscitation and outcomes were quantified using multivariable Poisson regression models (primary outcome: survival to hospital discharge [SHD]). In exploratory analyses, cubic splines further explored the relationship between CC metrics and outcomes to identify exploratory targets. RESULTS: Among 543 patients with evaluable data, the recommended rate target was met in 46.3%, depth in 25.7%, and CCF in 88.5%. Mean age was 3.6 (SD, 5.3) years, and 54.3% were male. None of these recommended CC targets were associated with SHD (rate: adjusted relative risk [aRR], 0.91 [95% CI, 0.78]; depth: aRR, 0.81 [95% CI, 0.51–1.29]; and CCF: aRR, 1.19 [95% CI, 0.92–1.54], respectively). Using cubic spline analyses, the following exploratory targets were identified and were associated with SHD: rate 130 to 160 cm ³ /min (aRR, 1.23 [95% CI, 1.04–1.46]), depths of 23 to 27 mm for patients 90% (aRR, 1.24 [1.03–1.49]). CONCLUSIONS: Currently recommended CC rate, depth, and fraction targets were not associated with SHD in this cohort. In contrast, we identified new potential pediatric cardiopulmonary resuscitation targets that were associated with SHD: rate 130 to 160 CC/min, depths of 23 to 27 mm for patients 90%. These criteria need validation in future prospective trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02837497.

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.

In Reply We agree that clinicians and educators should interpret our study¹ findings carefully and not conclude that these types of physiologic point-of-care CPR trainings and debriefings are ineffective based on a trial that was negative for the primary outcome. Dr McGaghie and colleagues have consistently and appropriately advocated that ideally, the successful knowledge, skill, and behavior acquisition of an individual would be tracked after training and linked to improved performance at the bedside, patient outcomes, and system/population effects. We agree that high-fidelity, time-intensive, comprehensive training programs are most likely to improve performance and behaviors of bedside teams in complex clinical scenarios.² Unfortunately, this approach lowers multicenter trial feasibility. Therefore, we sought to evaluate a simple bundle of evidence-informed interventions that was practical, sustainable, and likely to be widely adopted and disseminated following our trial. This decision was supported by a single-center study showing that this approach significantly improved outcomes.³ Moreover, a large body of science supports an intermittent spaced-learning approach, particularly in the field of CPR education.^4,5 In fact, the AHA now offers CPR recertification via a spaced-learning program as a result of prior investigations of this educational technique.