Adverse Tracheal Intubation Events in Critically Ill Underweight and Obese Children: Retrospective Study of the National Emergency Airway for Children Registry (2013-2020).

OBJECTIVES: Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children. DESIGN/SETTING: Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020. PATIENTS: Critically ill children, 0 to 17 years old, undergoing TI in PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002). CONCLUSIONS: In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events.

Evaluating Airway Management in Patients With Trisomy 21 in the PICU and Cardiac ICU: A Retrospective Cohort Study.

OBJECTIVES: Children with trisomy 21 often have anatomic and physiologic features that may complicate tracheal intubation (TI). TI in critically ill children with trisomy 21 is not well described. We hypothesize that in children with trisomy 21, TI is associated with greater odds of adverse airway outcomes (AAOs), including TI-associated events (TIAEs), and peri-intubation hypoxemia (defined as > 20% decrease in pulse oximetry saturation [Sp o2 ]). DESIGN: Retrospective database study using the National Emergency Airway Registry for Children (NEAR4KIDS). SETTING: Registry data from 16 North American PICUs and cardiac ICUs (CICUs), from January 2014 to December 2020. PATIENTS: A cohort of children under 18 years old who underwent TI in the PICU or CICU from in a NEAR4KIDS center. We identified patients with trisomy 21 and selected matched cohorts within the registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 8401 TIs in the registry dataset. Children with trisomy 21 accounted for 274 (3.3%) TIs. Among those with trisomy 21, 84% had congenital heart disease and 4% had atlantoaxial instability. Cervical spine protection was used in 6%. The diagnosis of trisomy 21 (vs. without) was associated with lower median weight 7.8 (interquartile range [IQR] 4.5-14.7) kg versus 10.6 (IQR 5.2-25) kg ( p < 0.001), and more higher percentage undergoing TI for oxygenation (46% vs. 32%, p < 0.001) and ventilation failure (41% vs. 35%, p = 0.04). Trisomy 21 patients had more difficult airway features (35% vs. 25%, p = 0.001), including upper airway obstruction (14% vs. 8%, p = 0.001). In addition, a greater percentage of trisomy 21 patients received atropine (34% vs. 26%, p = 0.004); and, lower percentage were intubated with video laryngoscopy (30% vs. 37%, p = 0.023). After 1:10 (trisomy 21:controls) propensity-score matching, we failed to identify an association difference in AAO rates (absolute risk difference -0.6% [95% CI -6.1 to 4.9], p = 0.822). CONCLUSIONS: Despite differences in airway risks and TI approaches, we have not identified an association between the diagnosis of trisomy 21 and higher AAOs.

Ketamine Use in the Intubation of Critically Ill Children with Neurological Indications: A Multicenter Retrospective Analysis.

BACKGROUND: Ketamine has traditionally been avoided for tracheal intubations (TIs) in patients with acute neurological conditions. We evaluate its current usage pattern in these patients and any associated adverse events. METHODS: We conducted a retrospective observational cohort study of critically ill children undergoing TI for neurological indications in 53 international pediatric intensive care units and emergency departments. We screened all intubations from 2014 to 2020 entered into the multicenter National Emergency Airway Registry for Children (NEAR4KIDS) registry database. Patients were included if they were under the age of 18 years and underwent TI for a primary neurological indication. Usage patterns and reported periprocedural composite adverse outcomes (hypoxemia < 80%, hypotension/hypertension, cardiac arrest, and dysrhythmia) were noted. RESULTS: Of 21,562 TIs, 2,073 (9.6%) were performed for a primary neurological indication, including 190 for traumatic brain injury/trauma. Patients received ketamine in 495 TIs (23.9%), which increased from 10% in 2014 to 41% in 2020 (p < 0.001). Ketamine use was associated with a coindication of respiratory failure, difficult airway history, and use of vagolytic agents, apneic oxygenation, and video laryngoscopy. Composite adverse outcomes were reported in 289 (13.9%) Tis and were more common in the ketamine group (17.0% vs. 13.0%, p = 0.026). After adjusting for location, patient age and codiagnoses, the presence of respiratory failure and shock, difficult airway history, provider demographics, intubating device, and the use of apneic oxygenation, vagolytic agents, and neuromuscular blockade, ketamine use was not significantly associated with increased composite adverse outcomes (adjusted odds ratio 1.34, 95% confidence interval CI 0.99-1.81, p = 0.057). This paucity of association remained even when only neurotrauma intubations were considered (10.6% vs. 7.7%, p = 0.528). CONCLUSIONS: This retrospective cohort study did not demonstrate an association between procedural ketamine use and increased risk of peri-intubation hypoxemia and hemodynamic instability in patients intubated for neurological indications.

Serial SARS-CoV-2 Antibody Titers in Vaccinated Dialysis Patients: Prevalence of Unrecognized Infection and Duration of Seroresponse.

Rationale & Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are likely underdiagnosed, but the degree of underdiagnosis among patients receiving maintenance dialysis is unknown. The durability of the immune response after the third vaccine dose in this population also remains uncertain. This descriptive study tracked antibody levels to (1) assess the rate of undiagnosed infections and (2) characterize seroresponse durability after the third dose. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2-vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies [anti-spike immunoglobulin (Ig) G] titers were assessed monthly after vaccination. Exposures: Two and 3 doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: Undiagnosed SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥100 BAU/mL, not associated with receipt of vaccine or diagnosed SARS-CoV-2 infection (by polymerase chain reaction test or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2,703 patients without previous coronavirus disease 2019 (COVID-19) who received an initial 2-dose vaccine series, 271 had diagnosed SARS-CoV-2 infections (3.4 per 10,000 patient-days) and 129 had undiagnosed SARS-CoV-2 infections (1.6 per 10,000 patient-days). Among 1,894 patients without previous COVID-19 who received a third vaccine dose, 316 had diagnosed SARS-CoV-2 infections (7.0 per 10,000 patient-days) and 173 had undiagnosed SARS-CoV-2 infections (3.8 per 10,000 patient-days). In both cohorts, anti-spike IgG levels declined over time. Of the initial 2-dose cohort, 66% had a titer of ≥500 BAU/mL in the first month, with 24% maintaining a titer of ≥500 BAU/mL at 6 months. Of the third dose cohort, 95% had a titer of ≥500 BAU/mL in the first month after the third dose, with 77% maintaining a titer of ≥500 BAU/mL at 6 months. Limitations: The assays used had upper limits. Conclusions: Among patients receiving maintenance dialysis, about 1 in every 3 SARS-CoV-2 infections was undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A 3-dose primary mRNA vaccine series optimizes seroresponse rate and durability. Plain-Language Summary: Patients receiving maintenance dialysis have been particularly vulnerable to COVID-19. Using serially measured antibodies, we found that a substantial proportion (about one-third) of SARS-CoV-2 infections among this population had been missed, both among those who had completed a 2-dose vaccine series and among those who had received a third vaccine dose. Such missed infections likely had only mild or minimal symptoms, but this failure to recognize all infections is concerning. Furthermore, vaccines have been effective among patients receiving dialysis, but our study additionally shows that the immune response wanes over time, even after a third dose. There is therefore a role for ongoing vigilance against this highly transmissible infection.

The Modified Clinical Progression Scale for Pediatric Patients: Evaluation as a Severity Metric and Outcome Measure in Severe Acute Viral Respiratory Illness.

OBJECTIVES: To develop, evaluate, and explore the use of a pediatric ordinal score as a potential clinical trial outcome metric in children hospitalized with acute hypoxic respiratory failure caused by viral respiratory infections. DESIGN: We modified the World Health Organization Clinical Progression Scale for pediatric patients (CPS-Ped) and assigned CPS-Ped at admission, days 2-4, 7, and 14. We identified predictors of clinical improvement (day 14 CPS-Ped ≤ 2 or a three-point decrease) using competing risks regression and compared clinical improvement to hospital length of stay (LOS) and ventilator-free days. We estimated sample sizes (80% power) to detect a 15% clinical improvement. SETTING: North American pediatric hospitals. PATIENTS: Three cohorts of pediatric patients with acute hypoxic respiratory failure receiving intensive care: two influenza (pediatric intensive care influenza [PICFLU], n = 263, 31 sites; PICFLU vaccine effectiveness [PICFLU-VE], n = 143, 17 sites) and one COVID-19 ( n = 237, 47 sites). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive mechanical ventilation rates were 71.4%, 32.9%, and 37.1% for PICFLU, PICFLU-VE, and COVID-19 with less than 5% mortality for all three cohorts. Maximum CPS-Ped (0 = home at respiratory baseline to 8 = death) was positively associated with hospital LOS ( p < 0.001, all cohorts). Across the three cohorts, many patients' CPS-Ped worsened after admission (39%, 18%, and 49%), with some patients progressing to invasive mechanical ventilation or death (19%, 11%, and 17%). Despite this, greater than 76% of patients across cohorts clinically improved by day 14. Estimated sample sizes per group using CPS-Ped to detect a percentage increase in clinical improvement were feasible (influenza 15%, n = 142; 10%, n = 225; COVID-19, 15% n = 208) compared with mortality ( n > 21,000, all), and ventilator-free days (influenza 15%, n = 167). CONCLUSIONS: The CPS-Ped can be used to describe the time course of illness and threshold for clinical improvement in hospitalized children and adolescents with acute respiratory failure from viral infections. This outcome measure could feasibly be used in clinical trials to evaluate in-hospital recovery.

Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.

Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. Methods: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Results: Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Conclusion: Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.

Implementation of Video Laryngoscope-Assisted Coaching Reduces Adverse Tracheal Intubation-Associated Events in the PICU.

OBJECTIVES: To evaluate implementation of a video laryngoscope (VL) as a coaching device to reduce adverse tracheal intubation associated events (TIAEs). DESIGN: Prospective multicenter interventional quality improvement study. SETTING: Ten PICUs in North America. PATIENTS: Patients undergoing tracheal intubation in the PICU. INTERVENTIONS: VLs were implemented as coaching devices with standardized coaching language between 2016 and 2020. Laryngoscopists were encouraged to perform direct laryngoscopy with video images only available in real-time for experienced supervising clinician-coaches. MEASUREMENTS AND MAIN RESULTS: The primary outcome was TIAEs. Secondary outcomes included severe TIAEs, severe hypoxemia (oxygen saturation < 80%), and first attempt success. Of 5,060 tracheal intubations, a VL was used in 3,580 (71%). VL use increased from baseline (29.7%) to implementation phase (89.4%; p < 0.001). VL use was associated with lower TIAEs (VL 336/3,580 [9.4%] vs standard laryngoscope [SL] 215/1,480 [14.5%]; absolute difference, 5.1%; 95% CI, 3.1-7.2%; p < 0.001). VL use was associated with lower severe TIAE rate (VL 3.9% vs SL 5.3%; p = 0.024), but not associated with a reduction in severe hypoxemia (VL 15.7% vs SL 16.4%; p = 0.58). VL use was associated with higher first attempt success (VL 71.8% vs SL 66.6%; p < 0.001). In the primary analysis after adjusting for site clustering, VL use was associated with lower adverse TIAEs (odds ratio [OR], 0.61; 95% CI, 0.46-0.81; p = 0.001). In secondary analyses, VL use was not significantly associated with severe TIAEs (OR, 0.72; 95% CI, 0.44-1.19; p = 0.20), severe hypoxemia (OR, 0.95; 95% CI, 0.73-1.25; p = 0.734), or first attempt success (OR, 1.28; 95% CI, 0.98-1.67; p = 0.073). After further controlling for patient and provider characteristics, VL use was independently associated with a lower TIAE rate (adjusted OR, 0.65; 95% CI, 0.49-0.86; p = 0.003). CONCLUSIONS: Implementation of VL-assisted coaching achieved a high level of adherence across the PICUs. VL use was associated with reduced adverse TIAEs.

Association of Asthma With Treatments and Outcomes in Children With Critical Influenza.

BACKGROUND: Hospitalization for severe influenza infection in childhood may result in postdischarge sequelae. OBJECTIVE: To evaluate inpatient management and postdischarge sequelae in children with critical respiratory illness owing to influenza with or without preexisting asthma. METHODS: This was a prospective, observational multicenter study of children (aged 8 months to 17 years) admitted to a pediatric intensive care or high-acuity unit (in November 2019 to April 2020) for influenza. Results were stratified by preexisting asthma. Prehospital status, hospital treatments, and outcomes were collected. Surveys at approximately 90 days after discharge evaluated postdischarge health resource use, functional status, and respiratory symptoms. RESULTS: A total of 165 children had influenza: 56 with preexisting asthma (33.9%) and 109 without it (66.1%; 41.1% and 39.4%, respectively, were fully vaccinated against influenza). Fifteen patients with preexisting asthma (26.7%) and 34 without it (31.1%) were intubated. More patients with versus without preexisting asthma received pharmacologic asthma treatments during hospitalization (76.7% vs 28.4%). Of 136 patients with 90-day survey data (82.4%; 46 with preexisting asthma [33.8%] and 90 without it [66.1%]), a similar proportion had an emergency department/urgent care visit (4.3% vs 6.6%) or hospital readmission (8.6% vs 3.3%) for a respiratory condition. Patients with preexisting asthma more frequently experienced asthma symptoms (78.2% vs 3.3%) and had respiratory specialist visits (52% vs 20%) after discharge. Of 109 patients without preexisting asthma, 10 reported receiving a new diagnosis of asthma (11.1%). CONCLUSIONS: Respiratory health resource use and symptoms are important postdischarge outcomes after influenza critical illness in children with and without preexisting asthma. Less than half of children were vaccinated for influenza, a tool that could mitigate critical illness and its sequelae.

NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.

BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity.

DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.

BACKGROUND: Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children. METHODS: We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score. RESULTS: Common variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity. CONCLUSIONS: We provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease.

Fine needle aspiration of hepatic angiomyolipoma with extramedullary hematopoiesis: A case report.

Angiomyolipoma, a perivascular epithelioid cell tumour, is easily identifiable as a benign tumour in the kidneys. However, when occurring in extrarenal sites it can mimic malignancy (Cancer Cytopathol. 2017;125:257). Pathologists must be aware of the classical morphological features of this lesion, its pitfalls in extrarenal sites, and the need for immunohistochemistry in order to establish the correct diagnosis (World J Gastroenterol. 2000;6:608). We report a case of angiomyolipoma with extramedullary hematopoiesis presenting as a large hepatic mass, diagnosed by cytology through endoscopic ultrasound guided fine needle aspiration. Our case exemplifies the classic cytological findings that are important in the differentiation between hepatic angiomyolipoma (HAML) and differentials in this organ such as hepatocellular carcinoma (HCC) and focal nodular hyperplasia. A brief literature review and comparison of significant features between HAML and HCC are presented.

Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children.

BACKGROUND: Predominance of 2 antigenically drifted influenza viruses during the 2019-2020 season offered an opportunity to assess vaccine effectiveness against life-threatening pediatric influenza disease from vaccine-mismatched viruses in the United States. METHODS: We enrolled children aged <18 years admitted to the intensive care unit with acute respiratory infection across 17 hospitals. Respiratory specimens were tested using reverse-transcription polymerase chain reaction for influenza viruses and sequenced. Using a test-negative design, we estimated vaccine effectiveness comparing odds of vaccination in test-positive case patients vs test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation. RESULTS: We enrolled 159 critically ill influenza case-patients (70% ≤8 years; 51% A/H1N1pdm09 and 25% B-Victoria viruses) and 132 controls (69% were aged ≤8 years). Among 56 sequenced A/H1N1pdm09 viruses, 29 (52%) were vaccine-mismatched (A/H1N1pdm09/5A+156K) and 23 (41%) were vaccine-matched (A/H1N1pdm09/5A+187A,189E). Among sequenced B-lineage viruses, majority (30 of 31) were vaccine-mismatched. Effectiveness against critical influenza was 63% (95% confidence interval [CI], 38% to 78%) and similar by age. Effectiveness was 75% (95% CI, 49% to 88%) against life-threatening influenza vs 57% (95% CI, 24% to 76%) against non-life-threating influenza. Effectiveness was 78% (95% CI, 41% to 92%) against matched A(H1N1)pdm09 viruses, 47% (95% CI, -21% to 77%) against mismatched A(H1N1)pdm09 viruses, and 75% (95% CI, 37% to 90%) against mismatched B-Victoria viruses. CONCLUSIONS: During a season when vaccine-mismatched influenza viruses predominated, vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children.

Intubation practice and outcomes among pediatric emergency departments: A report from National Emergency Airway Registry for Children (NEAR4KIDS).

BACKGROUND: Tracheal intubation (TI) practice across pediatric emergency departments (EDs) has not been comprehensively reported. We aim to describe TI practice and outcomes in pediatric EDs in contrast to those in intensive are units (ICUs) and use the data to identify quality improvement targets. METHODS: Consecutive TI encounters from pediatric EDs and ICUs in the National Emergency Airway Registry for Children (NEAR4KIDS) database from 2015 to 2018 were analyzed for patient, provider, and practice characteristics and outcomes: adverse TI-associated events (TIAEs), oxygen desaturation (SpO2 < 80%), and procedural success. A multivariable model identified factors associated with TIAEs in the ED. RESULTS: A total of 756 TIs in 13 pediatric EDs and 12,512 TIs in 51 pediatric/cardiac ICUs were reported. Median (interquartile range [IQR]) patient age for ED TIs was higher (32 [7-108] months) than that for ICU TIs (15 [3-91] months; p < 0.001). Proportion of TIs for respiratory decompensation (52% of ED vs. 64% ICU), shock (26% vs. 14%), and neurologic deterioration (30% vs. 11%) also differed by location. Limited neck mobility was reported more often in the ED (16% vs. 6%). TIs in the ED were performed more often via video laryngoscopy (64% vs. 29%). Adverse TIAE rates (15.6% ED, 14% ICU; absolute difference = 1.6%, 95% confidence interval [CI] = -1.1 to 4.2; p = 0.23) and severe TIAE rates (5.4% ED, 5.8% ICU; absolute difference = -0.3%, 95% CI = -2.0 to 1.3; p = 0.68) were not different. Oxygen desaturation was less commonly reported in ED TIs (13.6%) than ICU TIs (17%, absolute difference = -3.4%, 95% CI = -5.9 to -0.8; p = 0.016). Among ED TIs, shock as an indication (adjusted odds ratio [aOR] = 2.15, 95% CI = 1.26 to 3.65) and limited mouth opening (aOR = 1.74, 95% CI = 1.04 to 2.93) were independently associated with TIAEs. CONCLUSIONS: While TI characteristics vary between pediatric EDs and ICUs, outcomes are similar. Shock and limited mouth opening were independently associated with adverse TI events in the ED.

Facilitators and Barriers to Implementing Two Quality Improvement Interventions Across 10 Pediatric Intensive Care Units: Video Laryngoscopy-Assisted Coaching and Apneic Oxygenation.

To better understand facilitators and barriers to implementation of quality improvement (QI) efforts, this study examined 2 evidence-based interventions, video laryngoscopy (VL)-assisted coaching, and apneic oxygenation (AO). One focus group with frontline clinicians was held at each of the 10 participating pediatric intensive care units. Qualitative analysis identified common and unique themes. Intervention fidelity was monitored with a priori defined success as >50% VL-assisted coaching or >80% AO use for 3 consecutive months. Eighty percent of intensive care units with VL-assisted coaching and 20% with AO met this criteria during the study period. Common facilitator themes were adequate device accessibility, having a QI culture, and strong leadership. Common barrier themes included poor device accessibility and perception of delay in care. A consistently identified theme in the successful sites was strong QI leadership, while unsuccessful sites consistently identified insufficient education. These facilitators and barriers should be proactively addressed during dissemination of these interventions.

Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry.

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. DESIGN: Retrospective study. SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. CONCLUSIONS: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

Sustained Improvement in Tracheal Intubation Safety Across a 15-Center Quality-Improvement Collaborative: An Interventional Study From the National Emergency Airway Registry for Children Investigators.

OBJECTIVES: To evaluate the effect of a tracheal intubation safety bundle on adverse tracheal intubation-associated events across 15 PICUs. DESIGN: Multicenter time-series study. SETTING: PICUs in the United States. PATIENTS: All patients received tracheal intubations in ICUs. INTERVENTIONS: We implemented a tracheal intubation safety bundle as a quality-improvement intervention that includes: 1) quarterly site benchmark performance report and 2) airway safety checklists (preprocedure risk factor, approach, and role planning, preprocedure bedside "time-out," and immediate postprocedure debriefing). We define each quality-improvement phase as baseline (-24 to -12 mo before checklist implementation), benchmark performance reporting only (-12 to 0 mo before checklist implementation), implementation (checklist implementation start to time achieving > 80% bundle adherence), early bundle adherence (0-12 mo), and sustained (late) bundle adherence (12-24 mo). Bundle adherence was defined a priori as greater than 80% of checklist use for tracheal intubations for 3 consecutive months. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the adverse tracheal intubation-associated event, and secondary outcomes included severe tracheal intubation-associated events, multiple tracheal intubation attempts, and hypoxemia less than 80%.From January 2013 to December 2015, out of 19 participating PICUs, 15 ICUs (79%) achieved bundle adherence. Among the 15 ICUs, the adverse tracheal intubation-associated event rates were baseline phase: 217/1,241 (17.5%), benchmark reporting only phase: 257/1,750 (14.7%), early 0-12 month complete bundle compliance phase: 247/1,591 (15.5%), and late 12-24 month complete bundle compliance phase: 137/1,002 (13.7%). After adjusting for patient characteristics and clustering by site, the adverse tracheal intubation-associated event rate significantly decreased compared with baseline: benchmark: odds ratio, 0.83 (0.72-0.97; p = 0.016); early bundle: odds ratio, 0.80 (0.63-1.02; p = 0.074); and late bundle odds ratio, 0.63 (0.47-0.83; p = 0.001). CONCLUSIONS: Effective implementation of a quality-improvement bundle was associated with a decrease in the adverse tracheal intubation-associated event that was sustained for 24 months.

Impact of Failure of Noninvasive Ventilation on the Safety of Pediatric Tracheal Intubation.

OBJECTIVES: Noninvasive ventilation is widely used to avoid tracheal intubation in critically ill children. The objective of this study was to assess whether noninvasive ventilation failure was associated with severe tracheal intubation-associated events and severe oxygen desaturation during tracheal intubation. DESIGN: Prospective multicenter cohort study of consecutive intubated patients using the National Emergency Airway Registry for Children registry. SETTING: Thirteen PICUs (in 12 institutions) in the United States and Canada. PATIENTS: All patients undergoing tracheal intubation in participating sites were included. Noninvasive ventilation failure group included children with any use of high-flow nasal cannula, continuous positive airway pressure, or bilevel noninvasive ventilation in the 6 hours prior to tracheal intubation. Primary tracheal intubation group included children without exposure to noninvasive ventilation within 6 hours before tracheal intubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Severe tracheal intubation-associated events (cardiac arrest, esophageal intubation with delayed recognition, emesis with aspiration, hypotension requiring intervention, laryngospasm, pneumothorax, pneumomediastinum) and severe oxygen desaturation (< 70%) were recorded prospectively. The study included 956 tracheal intubation encounters; 424 tracheal intubations (44%) occurred after noninvasive ventilation failure, with a median of 13 hours (interquartile range, 4-38 hr) of noninvasive ventilation. Noninvasive ventilation failure group included more infants (47% vs 33%; p < 0.001) and patients with a respiratory diagnosis (56% vs 30%; p < 0.001). Noninvasive ventilation failure was not associated with severe tracheal intubation-associated events (5% vs 5% without noninvasive ventilation; p = 0.96) but was associated with severe desaturation (15% vs 9% without noninvasive ventilation; p = 0.005). After controlling for baseline differences, noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events (p = 0.35) or severe desaturation (p = 0.08). In the noninvasive ventilation failure group, higher FIO2 before tracheal intubation (≥ 70%) was associated with severe tracheal intubation-associated events. CONCLUSIONS: Critically ill children are frequently exposed to noninvasive ventilation before intubation. Noninvasive ventilation failure was not independently associated with severe tracheal intubation-associated events or severe oxygen desaturation compared to primary tracheal intubation.

Association Between Elevated RBC Distribution Width and Multiple Organ Dysfunction in Pediatric Critical Illness.

OBJECTIVES: RBC distribution width, a part of the complete blood count, has been shown in several published studies to be a strong biomarker of adverse outcomes. We sought to determine the association between admission RBC distribution width value and clinical outcomes including multiple organ dysfunction, mechanical ventilation days, PICU length of stay, and hospital length of stay in children admitted to the PICU. DESIGN: Single center, retrospective study. SETTING: A tertiary pediatric hospital in the United States. PATIENTS: All subjects admitted to the PICU from 2016 to 2017. EXCLUSIONS: Greater than 21 years old, pregnancy, and history of packed RBC transfusion within 120 days prior to admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand five-hundred one subjects were screened and 856 were included in data analysis. RBC distribution width value was categorized into four separate groups: group I (RBC distribution width < 13.4%), group II (13.4-14.3%), group III (14.4-15.7%), and group IV (RBC distribution width > 15.7%). Increased RBC distribution width at admission was associated with multiple organ dysfunction syndrome in the first 7 days (group I = 11.8% vs group IV = 30.1%; p < 0.0001) (odds ratio, 3.22; 95% CI, 1.95-5.30; p < 0.0001). Increased RBC distribution width was associated with increased median mechanical ventilation duration (group IV = 7 d vs group I = 5 d; p = 0.001), median hospital length of stay (group IV = 13 d vs group I = 5 d; p < 0.0001), and median PICU length of stay (group IV = 4 d vs group I = 3 d; p = 0.01). Mortality was not statistically associated with admission RBC distribution width (p = 0.12). CONCLUSIONS: PICU admission RBC distribution width values greater than 15.7% obtained upon admission to the PICU in patients who have not received a RBC transfusion are associated with multiple organ dysfunction syndrome in the first 7 days of admission, increased duration of mechanical ventilation, and increased hospital length of stay.

Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events.

OBJECTIVES: Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents. We also investigated if there was a dose dependence for any association between ketamine use and adverse hemodynamic events. DESIGN: We performed a retrospective analysis using prospectively collected observational data from the National Emergency Airway Registry for Children database from 2013 to 2017. SETTING: Forty international PICUs participating in the National Emergency Airway Registry for Children. PATIENTS: Critically ill children 0-17 years old who underwent tracheal intubation in a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The association between ketamine exposure as an induction agent and the occurrence of adverse hemodynamic events during tracheal intubation including dysrhythmia, hypotension, and cardiac arrest was evaluated. We used multivariable logistic regression to account for patient, provider, and practice factors with robust SEs to account for clustering by sites. Of 10,750 tracheal intubations, 32.0% (n = 3,436) included ketamine as an induction agent. The most common diagnoses associated with ketamine use were sepsis and/or shock (49.7%). After adjusting for potential confounders and sites, ketamine use was associated with fewer hemodynamic tracheal intubation associated adverse events compared with other agents (adjusted odds ratio, 0.74; 95% CI, 0.58-0.95). The interaction term between ketamine use and indication for shock was not significant (p = 0.11), indicating ketamine effect to prevent hemodynamic adverse events is consistent in children with or without shock. CONCLUSIONS: Ketamine use for tracheal intubation is associated with fewer hemodynamic tracheal intubation-associated adverse events.