The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

Immunogenicity of Monovalent mRNA-1273 and BNT162b2 Vaccines in Children Less Than 5 Years of Age.

BACKGROUND AND OBJECTIVES: The mRNA-based COVID-19 vaccines approved for use in children less than 5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to SARS-CoV-2 elicited by monovalent mRNA-based COVID-19 vaccines in young children. METHODS: We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected one month after primary vaccine series completion for measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicron subvariants (BA.1, BA.4/5). RESULTS: Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicron subvariants. Children with a prior history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicron subvariants, consistent with the occurrence of identified infections during the circulation of Omicron subvariants in the region. CONCLUSIONS: Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses one month after vaccination in young children. Further, prior infection significantly enhanced the strength of antibody responses to Omicron subvariants. Future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.

Factors Associated With Successful Extubation Readiness Testing in Children With Congenital Heart Disease.

BACKGROUND: In children with congenital heart disease, extubation readiness testing (ERT) is performed to evaluate the potential for liberation from mechanical ventilation. There is a paucity of data that suggests what mechanical ventilation parameters are associated with successful ERT. We hypothesized that ERT success would be associated with certain mechanical ventilator parameters. METHODS: Data on daily ERT assessments were recorded as part of a quality improvement project. In accordance with our respiratory therapist-driven ventilator protocol, patients were assessed daily for ERT eligibility and tested daily, if eligible. Mechanical ventilation parameters were categorized a priori to evaluate the differences in levels of respiratory support. The primary outcome was ERT success. RESULTS: A total of 780 ERTs from 320 subjects (median [interquartile range] age 2.5 [0.6-6.5] months and median weight [interquartile range] 4.2 [3.3-6.9] kg) were evaluated. A total of 528 ERTs (68%) were passed, 306 successful ERTs (58%) resulted in extubation, and 30 subjects (9.4%) were re-intubated. There were statistically significant differences in the ERT pass rate for ventilator mode, peak inspiratory pressure, Δ pressure, PEEP, mean airway pressure ([Formula: see text]), and dead-space-to-tidal-volume ratio (all P < .001) but not for [Formula: see text]. ERT success decreased with increases in peak inspiratory pressure, Δ pressure, PEEP, [Formula: see text], and dead-space-to-tidal-volume ratio. Logistic regression revealed neonates, Δ pressure ≥ 11 cm H2O, and [Formula: see text] > 10 cm H2O were associated with a decreased odds of ERT success, whereas children ages 1-5 years and an [Formula: see text] of 0.31-0.40 had increased odds of ERT success. CONCLUSIONS: ERT pass rates decreased as ventilator support increased; however, some subjects were able to pass ERT despite high ventilator support. We found that [Formula: see text] was associated with ERT success and that protocols should consider using [Formula: see text] instead of PEEP thresholds for ERT eligibility. Cyanotic lesions were not associated with ERT success, which suggests that patients with cyanotic heart disease can be included in ERT protocols.

Suicide and Self-Harm in Adolescents During the COVID-19 Pandemic: A U.S. Virtual Pediatric Systems, LLC, Database Study of PICU Admissions, 2016-2021.

OBJECTIVES: To characterize the epidemiology of suicide and self-harm among adolescents admitted to PICUs during the first 2 years of the COVID-19 pandemic in the United States. DESIGN: Descriptive analysis of a large, multicenter, quality-controlled database (Virtual Pediatric Systems [VPS]), and of a national public health dataset (U.S. Centers for Disease Control and Prevention web-based Wide-ranging ONline Data for Epidemiology Research [CDC WONDER]). SETTING: The 69 PICUs participating in the VPS database that contributed data for the entire the study period, January 1, 2016, to December 31, 2021. PATIENTS: Adolescents older than 12 years to younger than 18 years old admitted to a participating PICU during the study period with a diagnosis involving self-harm or a suicide attempt (VPS sample), or adolescent suicide deaths over the same period (CDC WONDER sample). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 10,239 suicide deaths and 7,692 PICU admissions for self-harm, including 5,414 admissions in the pre-pandemic period (Q1-2016 to Q1-2020) and 2,278 in the pandemic period (Q2-2020 to Q4-2021). Compared with the pre-pandemic period, there was no increase in the median (interquartile range) number of suicide deaths per quarter (429 [399-453] vs. 416 [390-482]) or PICU admissions for self-harm per quarter (315 [289-353] vs. 310 [286-387]) during the pandemic period, respectively. There was an increase in the ratio of self-harm PICU admissions to all-cause PICU admissions per quarter during the pandemic (1.98 [1.43-2.12]) compared with the pre-pandemic period per quarter (1.59 [1.46-1.74]). We also observed a significant decrease in all-cause PICU admissions per quarter early in the pandemic compared with the pre-pandemic period (16,026 [13,721-16,297] vs. 19,607 [18,371-20,581]). CONCLUSIONS: The number of suicide deaths and PICU admissions per quarter for self-harm remained relatively constant during the pandemic, while the number of all-cause PICU admissions per quarter decreased compared with the pre-pandemic period. The resultant higher ratio of self-harm admissions to all-cause PICU admissions may have contributed to the perception that more adolescents required critical care for mental health-related conditions early in the pandemic.

Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection.

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age. One Sentence Summary: Age is associated with distinct upper respiratory and peripheral blood transcriptional responses among children and adults with SARS-CoV-2 infection.

Noninvasive Ventilation or CPAP for Postextubation Support in Small Infants.

BACKGROUND: Infants with a high risk of extubation failure are often treated with noninvasive ventilation (NIV) or CPAP, but data on the role of these support modalities following extubation are sparse. This report describes our experience using NIV or CPAP to support infants following extubation in our pediatric ICUs (PICUs). METHODS: We performed a retrospective study of children < 10 kg receiving postextubation NIV or CPAP in our PICUs. Data on demographics, medical history, type of support, vital signs, pulse oximetry, near-infrared spectroscopy (NIRS), gas exchange, support settings, and re-intubation were extracted from the electronic medical record. Support was classified as prophylactic if planned before extubation and rescue if initiated within 24 h of extubation. We compared successfully extubated and re-intubated subjects using chi-square test for categorical variables and Mann-Whitney test for continuous variables. RESULTS: We studied 51 subjects, median age 44 (interquartile range 0.5-242) d and weight 3.7 (3-4.9) kg. There were no demographic differences between groups, except those re-intubated were more likely to have had cardiac surgery prior to admission (0% vs 14%, P = .040). NIV was used in 31 (61%) and CPAP in 20 (39%) subjects. Prophylactic support was initiated in 25 subjects (49%), whereas rescue support was needed in 26 subjects (51%). Twenty-two subjects (43%) required re-intubation. Re-intubation rate was higher for rescue support (58% vs 28%, P = .032). Subjects with a pH < 7.35 (4.3% vs 42.0%, P = .003) and lower somatic NIRS (39 [24-56] vs 62 [46-72], P = .02) were more likely to be re-intubated. The inspiratory positive airway pressure, expiratory positive airway pressure, and FIO2 were higher in subjects who required re-intubation. CONCLUSIONS: NIV or CPAP use was associated with a re-intubation rate of 43% in a heterogeneous sample of high-risk infants. Acidosis, cardiac surgery, higher FIO2 , lower somatic NIRS, higher support settings, and application of rescue support were associated with the need for re-intubation.

Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children: A Systematic Review and Network Meta-Analysis.

Importance: Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown. Objective: To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT). Data Sources: MEDLINE, Embase, and CINAHL Complete through May 2022. Study Selection: Randomized clinical trials that enrolled critically ill children receiving invasive mechanical ventilation for more than 24 hours and compared the efficacy of different modes of postextubation NRS. Data Extraction and Synthesis: Random-effects models were fit using a bayesian network meta-analysis framework. Between-group comparisons were estimated using odds ratios (ORs) or mean differences with 95% credible intervals (CrIs). Treatment rankings were assessed by rank probabilities and the surface under the cumulative rank curve (SUCRA). Main Outcomes and Measures: The primary outcome was EF (reintubation within 48 to 72 hours). Secondary outcomes were treatment failure (TF, reintubation plus NRS escalation or crossover to another NRS mode), pediatric intensive care unit (PICU) mortality, PICU and hospital length of stay, abdominal distension, and nasal injury. Results: A total of 11 615 citations were screened, and 9 randomized clinical trials with a total of 1421 participants were included. Both CPAP and HFNC were found to be more effective than COT in reducing EF and TF (CPAP: OR for EF, 0.43; 95% CrI, 0.17-1.0 and OR for TF 0.27, 95% CrI 0.11-0.57 and HFNC: OR for EF, 0.64; 95% CrI, 0.24-1.0 and OR for TF, 0.34; 95% CrI, 0.16- 0.65). CPAP had the highest likelihood of being the best intervention for both EF (SUCRA, 0.83) and TF (SUCRA, 0.91). Although not statistically significant, BiPAP was likely to be better than COT for preventing both EF and TF. Compared to COT, CPAP and BiPAP were reported as showing a modest increase (approximately 3%) in nasal injury and abdominal distension. Conclusions and Relevance: The studies included in this systematic review and network meta-analysis found that compared with COT, EF and TF rates were lower with modest increases in abdominal distension and nasal injury. Of the modes evaluated, CPAP was associated with the lowest rates of EF and TF.

Association Between Dead Space to Tidal Volume Ratio and Duration of Respiratory Support After Extubation in Critically Ill Children.

BACKGROUND: The dead-space-to-tidal-volume ratio (VD/VT) has been used to successfully predict extubation failure in children who are critically ill. However, a singular reliable measure to predict the level and duration of respiratory support after liberation from invasive mechanical ventilation has remained elusive. The objective of this study was to evaluate the association between VD/VT and the duration of postextubation respiratory support. METHODS: This was a retrospective cohort study of subjects who were mechanically ventilated and admitted to a single-center pediatric ICU between March 2019 and July 2021, and who had been extubated with a recorded VD/VT. A cutoff of 0.30 was chosen a priori, with subjects divided into 2 groups, VD/VT < 0.30 and VD/VT ≥ 0.30, and postextubation respiratory support was recorded at specified time intervals (24 h, 48 h, 72 h, 7 d, and 14 d). RESULTS: We studied 54 subjects. Those with VD/VT ≥ 0.30 had a significantly longer median (interquartile range) duration of respiratory support after extubation (6 [3-14] d vs 2 [0-4] d; P = .001) and longer median (interquartile range) ICU stay (14 [12-19] d vs 8 [5-22] d; P = .046) versus the subjects with VD/VT < 0.30. The distribution of respiratory support did not differ significantly between VD/VT at the time of extubation (P = .13) or at 14 d after extubation (P = .21) but was significantly different during the intervening time points after extubation (24 h [P = .01], 48 h [P < .001], 72 h [P < .001], and 7 d [P = .02]). CONCLUSIONS: VD/VT was associated with the duration and level of respiratory support needed after extubation. Prospective studies are needed to establish if VD/VT can successfully predict the level of respiratory support after extubation.

Feasibility of a Multi-Center Respiratory Therapist Endotracheal Intubation Study.

BACKGROUND: Respiratory therapists (RTs) have historically performed safe and effective intubations, yet there are limited multi-center data assessing their intubation performance. Multi-center data can be used to compare RT intubation performance to that of other professions and identify quality improvement opportunities at hospitals where RTs perform intubation. We aimed to explore the feasibility of a multi-center collaborative to evaluate RT intubation outcomes. METHODS: A data collection tool was developed by the authors and implemented at two institutions. Following institutional review board approval at each center and completion of data-use sharing agreements, data were collected between May 25, 2020-April 30, 2022, and combined for analysis. Descriptive statistics were used to compare overall success rate, first-attempt success rate, adverse events (AEs), and type of laryngoscopy. RESULTS: There were a total of 689 intubation courses where RTs made an attempt, 363 from center A and 326 from center B. Center A captured 85% of all RT intubation courses, and center B captured 63%. Overall, RTs were successful in 98% of attempts. RTs made 86% of initial attempts. The most common indications for intubation were cardiac arrest (42%) and respiratory failure (31%). Videolaryngoscopy was used during 65% of initial attempts and was associated with higher first-attempt success rate, higher overall success rate, and fewer AEs. Airway-related adverse event rate was 8.7%; physiologic AE rate was 16%, and desaturation rate was 11%. CONCLUSIONS: A collaborative examining RTs intubation performance was successfully initiated at 2 separate facilities. Intubations performed by RTs had a high success rate, with AE rates comparable to published results from other types of providers.

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

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.

Operational Definitions Related to Pediatric Ventilator Liberation.

BACKGROUND: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices. RESEARCH QUESTION: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches? STUDY DESIGN AND METHODS: A panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. RESULTS: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support. INTERPRETATION: We propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

Association Between Pressure Support During Extubation Readiness Testing and Time to First Extubation in Children With Congenital Heart Disease.

BACKGROUND: Extubation readiness testing (ERT) is often performed in children with congenital heart disease prior to liberation from mechanical ventilation. The ideal ERT method in this population is unknown. We recently changed our ERT method from variable (10, 8, or 6 cm H2O, depending on endotracheal tube size) to fixed (5 cm H2O) pressure support (PS). Our study assessed the association between this change and time to first extubation and need for re-intubation. METHODS: We studied 2 temporally distinct cohorts, one where ERT was conducted with variable PS and another using PS fixed at 5 cm H2O. Data were prospectively collected as part of a quality improvement project. The primary outcome was time to first extubation. Secondary outcomes were need for re-intubation and percentage of successful ERTs. We performed Poisson regression or logistic regression for the association between PS during ERT and time to first extubation or re-intubation, respectively. RESULTS: We included 320 subjects, 186 in the variable PS group and 152 in fixed PS group. In unadjusted analysis, median time to first extubation was longer in the fixed PS group compared to the variable PS group (4.1 [2.0-7.1] d vs 3.1 [1.1-5.9] d, P = .02), and there was no difference in re-intubation rate (11% vs 8%, P = .34). Subjects in the fixed PS group were significantly more likely to be mechanically ventilated after cardiac arrest, have a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) category of 4 or 5, be extubated on day shift, receive enteral feeds at extubation, have higher respiratory support at extubation, and higher dead-space-to-tidal-volume ratio. After controlling for these variables in multivariable regression, we found no association between the choice of PS and time to first extubation or re-intubation. CONCLUSIONS: The use of a fixed PS of 5 cm H2O instead of variable PS during ERT was not associated with longer time to first extubation or extubation failure.

Commentary on High-Flow Nasal Cannula and Continuous Positive Airway Pressure Practices After the First-Line Support for Assistance in Breathing in Children Trials.

Continuous positive airway pressure (CPAP) and heated humidified high-flow nasal cannula (HFNC) are commonly used to treat children admitted to the PICU who require more respiratory support than simple oxygen therapy. Much has been published on these two treatment modalities over the past decade, both in Pediatric Critical Care Medicine (PCCM ) and elsewhere. The majority of these studies are observational analyses of clinical, administrative, or quality improvement datasets and, therefore, are only able to establish associations between exposure to treatment and outcomes, not causation. None of the initial randomized clinical trials comparing HFNC and CPAP were definitive due to their relatively small sample sizes with insufficient power for meaningful clinical outcomes (e.g., escalation to bilevel noninvasive ventilation or intubation, duration of PICU-level respiratory support, mortality) and often yielded ambiguous findings or conflicting results. The recent publication of the First-Line Support for Assistance in Breathing in Children (FIRST-ABC) trials represented a major step toward understanding the role of CPAP and HFNC use in critically ill children. These large, pragmatic, randomized clinical trials examined the efficacy of CPAP and HFNC either for "step up" (i.e., escalation in respiratory support) during acute respiratory deterioration or for "step down" (i.e., postextubation need for respiratory support) management. This narrative review examines the body of evidence on HFNC published in PCCM , contextualizes the findings of randomized clinical trials of CPAP and HFNC up to and including the FIRST-ABC trials, provides guidance to PICU clinicians on how to implement the literature in current practice, and discusses remaining knowledge gaps and future research priorities.