Christopher John L. Newth

IMPORTANCE: Viral bronchiolitis is the leading cause of nonelective admission to the PICU. Guidelines recommend management that focuses on supportive care. Evidence suggests that inhaled epinephrine may reduce lower airways resistance and work of breathing in critical bronchiolitis. It has been demonstrated at one institution that it is feasible to administer continuous inhaled epinephrine (CIE) via heated high-flow nasal cannula (HFNC). OBJECTIVES: To describe the demographic and clinical characteristics of patients with bronchiolitis who received CIE and assess their physiologic response to treatment compared with patients who received conventional therapy. DESIGN, SETTING, AND PARTICIPANTS: We performed a single-center retrospective cohort study of previously healthy children 0–2 years old admitted to the PICU with diagnosis of bronchiolitis from 2017 to 2023. MAIN OUTCOMES AND MEASURES: Physiologic response to treatment was assessed via analysis of vital signs and use of respiratory rate, oxygenation, heart rate (ROX-HR) index. RESULTS: One hundred ninety-three patients were included in the study. Patients who received CIE were younger (median age, 4 vs. 7 mo old; p = 0.01) and smaller (7.0 vs. 8.4 kg; p = 0.06), presented with higher initial peak respiratory rates (70 vs. 50 beats/min; p < 0.0001), and had longer ICU stays (3.4 vs. 1.8 d; p < 0.001). Patients treated with CIE exhibited overall higher respiratory rates and lower ROX-HR indices, indicating more severe illness. Within the first 48 hours of treatment, patients receiving CIE demonstrated a more rapid improvement in both respiratory rate and ROX-HR index compared with those receiving conventional therapy. CONCLUSIONS AND RELEVANCE: In this cohort, CIE was used as novel therapy for younger, smaller patients with more severe bronchiolitis on presentation to the PICU. The physiologic changes suggest potential benefit of this therapy for patients who are not improving with conventional HFNC therapy.

Introduction: Pediatric critical asthma is one of the most common pediatric illnesses in children admitted to the pediatric ward and pediatric intensive care unit (PICU). Adjunct intravenous (IV) bronchodilators are often used when initial management with systemic corticosteroids and inhaled short‐acting beta agonists (SABA) fail to provide improvement in a patient's clinical condition. While the recent guidelines gave recommendations for the use of different IV bronchodilators compared to placebo, it did not include ranking on which one should be used as first‐line or second‐line agent. The aim of this network meta‐analysis is to determine the effect of IV bronchodilators on patient‐centered outcomes and rank medications based on their effectiveness in these outcomes. Methods: A systematic review was conducted using three databases MEDLINE, Embase, and CINAHL to identify randomized control trials examining the use of IV magnesium sulfate (MgSO ₄ ), IV methylxanthines (aminophylline or theophylline), IV SABA (salbutamol, terbutaline) in pediatric critical asthma patients. Bayesian network metanalytic framework was used to compare the interventions. Results are reported as odds ratio (OR) or mean difference (MD) and 95% Credible Interval (CrI). Results: Twelve trials ( n = 852) were included in the network meta‐analysis. Largest reduction in hospital length of stay (LOS), PICU admission, and PICU LOS were noted with IV MgSO ₄ ; (MD: −3.1 days, 95% CrI: −6.9 days to 0.13 days), (OR 0.21; 95% CrI 0.02, 1.3), and (MD: −4.0 days, 95% CrI: −7.1 days to −1.2 days) respectively. IV MgSO ₄ was ranked first in three outcomes of interest with Surface Under the Cumulative Ranking curve (SUCRA) of 0.884 for hospital LOS, 0.919 for PICU admission, and 0.957 for PICU LOS. For preventing intubation, IV SABA was ranked the highest (SUCRA 0.995), but the only study with IV SABA had zero intubation events. In a sensitivity analysis that excluded studies with zero events, the intubation rate was lowest with IV MgSO ₄ (OR 0.10; 95% CrI 0.003, 0.88) and it was ranked the best treatment (SUCRA 0.921). Conclusions: In this network meta‐analysis comparing different IV adjunct bronchodilators, IV MgSO ₄ was ranked first followed by IV SABA, and then IV methylxanthines. Given these findings and the favorable safety profile, ease of use, and low cost, IV MgSO ₄ appears most promising the first adjunct IV bronchodilator, however, further large high‐quality trials are still needed before it can be endorsed as routine first‐line agent.

Objective: Our aim was to confirm whether extreme hyperoxemic events had been associated with excess mortality in our diverse critical care population.Methods: Retrospective analysis of 9 years of data collected in the pediatric and cardiothoracic ICUs in Children's Hospital Los Angeles was performed. The analysis was limited to those mechanically ventilated for at least 24 h, with at least 1 arterial blood gas measurement. An extreme hyperoxemic event was defined as a PaO₂ of ≥300 torr. Multivariable logistic regression was used to assess the association of extreme hyperoxemia events and mortality, adjusting for confounding variables. Selected a-priori, these were Pediatric Risk of Mortality III predicted mortality, general or cardiothoracic ICU, number of blood gas measurements, as well as an abnormal blood gas measurements (pH < 7.25, pH > 7.45, and PaO₂ < 50 torr).Results: There were 4,003 admissions included with a predicted mortality of 7.1% and an actual mortality of 9.7%. Their care was associated with 75,129 blood gas measurements, in which abnormal measurements were common. With adjustments for these covariates, any hyperoxemic event was associated with excess mortality (p < 0.001). Excess mortality increased with multiple hyperoxemic events (p < 0.046). Additionally, treatment resulting in SpO₂ > 98% markedly increased the risk of a hyperoxemic event.Conclusion: Retrospective analysis of critical care admissions showed that extreme hyperoxemic events were associated with higher mortality. Supplemental oxygen levels resulting in SpO₂ > 98% should be avoided.

The utility of decision tree machine learning in exploring the interactions among the SpO₂ target range, neonatal maturity, and oxemic-risk is demonstrated. METHODS: This observational study used 3 years of paired age-SpO₂-PaO₂ data from a neonatal ICU. The CHAID decision tree method was used to explore the interaction of postmenstrual age (PMA) on the risk of extreme arterial oxygen levels at six different potential SpO₂ target ranges (88–92%, 89–93%, 90–94%, 91–95%, 92–96% and 93–97%). Risk was calculated using a severity-weighted average of arterial oxygen outside the normal range for neonates (50–80 mmHg). RESULTS: In total, 7500 paired data points within the potential target range envelope were analyzed. The two lowest target ranges were associated with the highest risk, and the ranges of 91–95% and 92–96% were associated with the lowest risk. There were shifts in the risk associated with PMA. All the target ranges showed the lowest risk at ≥42 weeks PMA. The lowest risk for preterm infants was within a target range of 92–96% with a PMA of ≤34 weeks. CONCLUSIONS: This study demonstrates the utility of decision tree analytics. These results suggest that SpO₂ target ranges that are different from typical range might reduce morbidity and mortality. Further research, including prospective randomized trials, is warranted.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients’ readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Approximately 10 000 children experience in-hospital or out-of-hospital cardiac arrest annually in the US.^1,2 Children with return of spontaneous circulation (ROSC) are at high risk of neurological morbidity and death due to global hypoxic-ischemic brain injury.³ Accurate early understanding of the risk of neurological injury could support clinician and family decision-making and treatment. However, a standardized validated approach is lacking.⁴

Patients supported by mechanical ventilation require frequent invasive blood gas samples to monitor and adjust the level of support. We developed a transparent and novel blood gas estimation model to provide continuous monitoring of blood pH and arterial CO₂ in between gaps of blood draws, using only readily available noninvasive data sources in ventilated patients. The model was trained on a derivation dataset (1,883 patients, 12,344 samples) from a tertiary pediatric intensive care center, and tested on a validation dataset (286 patients, 4030 samples) from the same center obtained at a later time. The model uses pairwise non-linear interactions between predictors and provides point-estimates of blood gas pH and arterial CO₂ along with a range of prediction uncertainty. The model predicted within Clinical Laboratory Improvement Amendments of 1988 (CLIA) acceptable blood gas machine equivalent in 74% of pH samples and 80% of PCO₂ samples. Prediction uncertainty from the model improved estimation accuracy by 15% by identifying and abstaining on a minority of high-uncertainty samples. The proposed model estimates blood gas pH and CO₂ accurately in a large percentage of samples. The model’s abstention recommendation coupled with ranked display of top predictors for each estimation lends itself to real-time monitoring of gaps between blood draws, and the model may help users determine when a new blood draw is required and delay blood draws when not needed.