Predictors of Failure of Noninvasive Ventilation in Critically Ill Children.

Noninvasive ventilation (NIV) is a common modality employed to treat acute respiratory failure. Most data guiding its use is extrapolated from adult studies. We sought to identify clinical predictors associated with failure of NIV, defined as requiring intubation. This single-center retrospective observational study included children admitted to pediatric intensive care unit (PICU) between July 2014 and June 2016 treated with NIV, excluding postextubation. A total of 148 patients was included. Twenty-seven (18%) failed NIV. There was no difference between the two groups with regard to age, gender, comorbidities, or etiology of acute respiratory failure. Those that failed had higher admission pediatric risk of mortality ( p = 0.01) and pediatric logistic organ dysfunction ( p = 0.002) scores and higher fraction of inspired oxygen (FiO 2 ; p = 0.009) at NIV initiation. Failure was associated with lack of improvement in tachypnea. At 6 hours of NIV, the failure group had worsening tachypnea with a median increase in respiratory rate of 8%, while the success group had a median reduction of 18% ( p = 0.06). Multivariable Cox's proportional hazard models revealed FiO 2 at initiation and worsening respiratory rate at 1- and 6-hour significant risks for failure of NIV. Failure was associated with a significantly longer PICU length of stay (success [2.8 days interquartile range (IQR): 1.7, 5.5] vs. failure [10.6 days IQR: 5.6, 13.2], p < 0.001). NIV can be successfully employed to treat acute respiratory failure in pediatric patients. There should be heightened concern for NIV failure in hypoxemic patients whose tachypnea is unresponsive to NIV. A trend toward improvement should be closely monitored.

Decision-Making and Ethical Considerations of Tracheostomy and Chronic Mechanical Ventilation in Children With Acute Neurological Injury.

The decisions around whether or not to provide tracheostomy and chronic mechanical ventilation to children with acute neurologic injury are difficult for medical providers and surrogate decision makers. Consideration of the 4 primary principles of medical ethics-autonomy, beneficence, non-maleficence, and justice-can provide a framework from which constructive discussions can form. Determination of the goals of care is a good first step in navigating these complex decisions. A shared decision model should be used, including education of decision-makers by medical providers and appropriate recommendations based on the stated goals of care. In this paper, 2 illustrative cases are discussed highlighting the utility of this decision-making framework.

Early-Onset Ventilator-Associated Pneumonia in Pediatric Severe Traumatic Brain Injury.

BACKGROUND: Early-onset ventilator-associated pneumonia (VAP) is associated with poor outcomes in patients with severe traumatic brain injury (TBI). The primary aim of this study was to describe VAP, including the microbiology of VAP and differences in frequency of VAP when various definitions are applied. The secondary aim was to determine the clinical variables associated with the development of VAP in children with severe TBI. METHODS: This is a retrospective cohort study at a quaternary referral children's hospital with a level I trauma center designation. Inclusion criteria were patients aged 0-18 years admitted to the pediatric intensive care unit between 2015 and 2020 with severe TBI requiring at least 2 days of invasive ventilation. VAP was defined by using Center of Disease Control (CDC) definition or clinical VAP, based on physician diagnosis. We compared general demographics, reviewed trauma and injury data, and outcomes to assess any differences between patients with VAP and non-VAP patients. Associations were tested with regression models. RESULTS: After applying all inclusion and exclusion criteria, 90 patients were included in the analysis. Patients with VAP were older (8.5 vs. 5.6 years, P = 0.03). Patients with VAP were less likely to have suffered from abusive head trauma (P = 0.01). Patients who received continuous neuromuscular blockade or targeted temperature management did not have different frequencies of VAP. CDC-defined VAP was diagnosed in 27% of patients. Number of patients with VAP increased to 41% for physician-diagnosed or clinical VAP. Methicillin-sensitive Staphylococcus aureus was the most common isolate grown, followed by Hemophilus influenza, with most VAP occurring on days 2-5 of intubation. VAP was not associated with mortality but was associated with worse functional status scale in patients who survived to discharge (8 vs. 7.5, P = 0.048). Over a cumulative period of days, nebulized 3% and albuterol were associated with decreased incidence of VAP. CONCLUSIONS: Ventilator-associated pneumonia occurs commonly in children with severe TBI, with rates of 27-41%, depending on CDC-defined VAP or clinical VAP. The discrepancy between clinical VAP and CDC-defined VAP further illustrates the need for a standardized definition for VAP. Although most interventions were not associated with VAP, nebulized 3% saline and albuterol were associated with reduced incidence of VAP; future investigation is needed to determine whether mucolytic agents can decrease the rate of VAP in children with severe TBI.

Airway microbiome dynamics and relationship to ventilator-associated infection in intubated pediatric patients.

BACKGROUND: Little is known about the airway microbiome in intubated mechanically ventilated children. We sought to characterize the airway microbiome longitudinally and in association with clinical variables and possible ventilator-associated infection (VAI). METHODS: Serial tracheal aspirate samples were prospectively obtained from mechanically ventilated subjects under 3 years old from eight pediatric intensive care units in the United States from June 2017 to July 2018. Changes in the tracheal microbiome were analyzed by sequencing bacterial 16S ribosomal RNA gene relative to subject demographics, diagnoses, clinical parameters, outcomes, antibiotic treatment, and the Ventilator-Associated InfectioN (VAIN) score. RESULTS: A total of 221 samples from 58 patients were processed and 197 samples met the >1000 reads criteria (89%), with an average of 43,000 reads per sample. The median number of samples per subject was 3 (interquartile range [IQR]: 2-5), with a median VAIN score of 2 (IQR: 1-3). Proteobacteria was the highest observed phyla throughout the intubation period, followed by Firmicutes and Actinobacteria. Alpha diversity was negatively associated with days of intubation (p = .032) and VAIN score (p = .016). High VAIN scores were associated with a decrease of Mycobacterium obuense, and an increase of Streptococcus peroris, Porphyromonadaceae family (unclassified species), Veillonella atypica, and several other taxa. No specific pattern of microbiome composition related to clinically diagnosed VAIs was observed. CONCLUSIONS: Our data demonstrate decreasing alpha diversity with increasing VAIN score and days of intubation. No specific microbiome pattern was associated with clinically diagnosed VAI.

Compliance With an Antibiotic Guideline for Suspected Ventilator-Associated Infection: The Ventilator-Associated INfection (VAIN2) Study.

OBJECTIVES: To evaluate a guideline for antibiotic decisions in children with suspected ventilator-associated infection. DESIGN: Prospective, observational cohort study conducted in 22 PICUs in the United States and Canada. SETTING: PICUs in 22 hospitals from April 2017 to January 2019. SUBJECTS: Children less than 3 years old on mechanical ventilation greater than 48 hours who had respiratory secretions cultured and antibiotics initiated for suspected ventilator-associated infection. INTERVENTIONS: After baseline data collection in children with suspected ventilator-associated infection (Phase 1), a consensus guideline was developed for advising antibiotic continuation or stopping at 48-72 hours (Phase 2) and implemented (Phase 3). Guideline-based antibiotic recommendations were provided to the treating clinicians once clinical and microbiologic data were available. Demographic and outcome data were collected, and guideline compliance and antibiotic utilization evaluated for Phase 1 and Phase 3. MEASUREMENTS AND MAIN RESULTS: Despite education and implementation efforts, guideline-concordant antibiotic management occurred in 158 of 227 (70%) Phase 3 subjects compared with 213 of 281 (76%) in Phase 1. Illness severity and positive respiratory cultures were the primary determinants of antibiotic continuation. For subjects with a positive respiratory culture but a score for which antibiotic discontinuation was recommended (score ≤ 2), only 27% of Phase 3 subjects had antibiotics discontinued. Antibiotic continuation was not associated with improved outcomes in these subjects and was associated with significantly longer duration of ventilation (median 5.5 d longer) and PICU stay (5 d longer) in the overall study population. Positive respiratory cultures were not associated with outcomes irrespective of antibiotic treatment. CONCLUSIONS: Antibiotic guideline efficacy and safety remain uncertain due to clinician failure to follow the guideline, instead primarily relying on respiratory culture results. Strategies to overcome clinician perceptions of respiratory cultures and other barriers will be vital for improving guideline adherence and antibiotic use in suspected ventilator-associated infection in future studies.

Health Care Resource Utilization for Children Requiring Prolonged Mechanical Ventilation via Tracheostomy.

BACKGROUND: More children are discharged from ICUs on prolonged mechanical ventilation (PMV) via tracheostomy than ever before. These patients have long hospitalizations with high resource expenditure. Our objective was to describe the characteristics of these resource-intensive patients and to evaluate their costs of care. We hypothesized that subjects requiring PMV for neurologic diagnoses would have higher costs, longer hospital length of stay (LOS), and worse outcomes than those with primarily respiratory diagnoses. METHODS: We identified 50 pediatric subjects between January 2015 and December 2017 at our institution who had a new tracheostomy placement and were enrolled in a home mechanical ventilation program. Collected data included demographics, indication for tracheostomy, LOS, hospital costs, readmissions, and outcomes. We also compared subjects who required PMV for respiratory diagnoses versus neurologic diagnoses. RESULTS: Of 50 subjects, 41 were < 12 months old at the time of tracheostomy. Thirty-four subjects had a respiratory diagnosis requiring PMV, 14 had a neurologic diagnosis, and 2 had a cardiac diagnosis. The total initial hospitalization cost was $31,133,582, which averages to $622,671 per subject. The average initial hospitalization LOS was 155 d. Respiratory subjects had longer LOS and higher average costs than neurologic subjects. The average readmission rate was 2.16 per subject in the first year after discharge, and the average readmission cost per subject was $73,144. Eight subjects died in the first year after discharge, and 4 suffered a serious morbidity. CONCLUSIONS: This descriptive study evaluated the social and medical characteristics of subjects being discharged from the pediatric ICU with PMV via tracheostomy, as well as quantified the financial impact of their care. Those requiring PMV for neurologic diagnoses had shorter hospital LOS and lower hospital costs than those with respiratory diagnoses. No definitive differences in outcomes were found.

Development of an Antibiotic Guideline for Children With Suspected Ventilator-Associated Infections.

OBJECTIVES: To develop a guideline for the decision to continue or stop antibiotics at 48-72 hours after their initiation in children with suspected ventilator-associated infection. DESIGN: Prospective, multicenter observational data collection and subsequent development of an antibiotic guideline. SETTING: Twenty-two PICUs. PATIENTS: Children less than 3 years old receiving mechanical ventilation who underwent clinical testing and initiation of antibiotics for suspected ventilator-associated infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Phase 1 was a prospective data collection in 281 invasively ventilated children with suspected ventilator-associated infection. The median age was 8 months (interquartile range, 4-16 mo) and 75% had at least one comorbidity. Phase 2 was development of the guideline scoring system by an expert panel employing consensus conferences, literature search, discussions with institutional colleagues, and refinement using phase 1 data. Guideline scores were then applied retrospectively to the phase 1 data. Higher scores correlated with duration of antibiotics (p < 0.001) and higher PEdiatric Logistic Organ Dysfunction 2 scores (p < 0.001) but not mortality, PICU-free days or ventilator-free days. Considering safety and outcomes based on the phase 1 data and aiming for a 25% reduction in antibiotic use, the panel recommended stopping antibiotics at 48-72 hours for guideline scores less than or equal to 2, continuing antibiotics for scores greater than or equal to 6, and offered no recommendation for scores 3, 4, and 5. The acceptability and effect of these recommendations on antibiotic use and outcomes will be prospectively tested in phase 3 of the study. CONCLUSIONS: We developed a scoring system with recommendations to guide the decision to stop or continue antibiotics at 48-72 hours in children with suspected ventilator-associated infection. The safety and efficacy of the recommendations will be prospectively tested in the planned phase 3 of the study.

Implementing a Respiratory Therapist-Driven Continuous Albuterol Weaning Protocol in the Pediatric ICU.

BACKGROUND: Status asthmaticus is one of the most frequent admission diagnoses in the pediatric ICU (PICU). Collaboration between respiratory therapists (RTs) and physicians may help efficiently deliver care to a patient in status asthmaticus. The Pediatric Asthma Severity Score (PASS) is a measure of severity of a patient's asthma exacerbation at a point in time. The aim of this quality improvement initiative was to establish an RT-driven continuous albuterol weaning protocol using the PASS score. We hypothesized that this would decrease the duration of continuous albuterol without increasing adverse events. METHODS: This was a single-center implementation study in the PICU of a quaternary care children's hospital. Patients with a diagnosis of status asthmaticus who met criteria on continuous albuterol between September 2015 and September 2017 were included. An interdisciplinary team established the protocol, order sets, documentation, and education for involved staff. Qualifying subjects were assessed by an RT per protocol and assigned a PASS score, and the albuterol dose was adjusted on the basis of the PASS score. RESULTS: We compared 104 subjects studied before the implementation of this protocol (September 2015 to August 2016) to 117 subjects after the implementation of this protocol (September 2016 to October 2017). Median (interquartile range) duration of continuous albuterol in the PICU post-implementation was unchanged compared to pre-implementation: 12.1 (7.2-21.0) h versus 11.1 (6-19) h (P = .22). Median PICU length of stay was also unchanged post-implementation compared to pre-implementation: 19.5 (14.3-29.7) h versus 23.2 (15.2-31.3) h (P = .16). Using control charts, these processes were stable. There was no difference in adverse events. CONCLUSIONS: An interprofessionally-developed, RT-driven continuous albuterol weaning protocol can be implemented without negatively impacting duration of continuous albuterol or PICU length of stay and without increasing adverse events.

Pediatric Ventilator-Associated Events: Analysis of the Pediatric Ventilator-Associated Infection Data.

OBJECTIVES: To compare the prevalence of infection applying the proposed pediatric ventilator-associated events criteria versus clinician-diagnosed ventilator-associated infection to subjects in the pediatric ventilator-associated infection study. DESIGN: Analysis of prospectively collected data from the pediatric ventilator-associated infection study. SETTING: PICUs of 47 hospitals in the United States, Canada, and Australia. PATIENTS: Two-hundred twenty-nine children ventilated for greater than 48 hours who had respiratory secretion cultures performed to evaluate for suspected ventilator-associated infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Applying the proposed pediatric ventilator-associated event criteria, 15 of 229 subjects in the ventilator-associated infection study qualified as "ventilator-associated condition" and five of 229 (2%) met criteria for "infection-related ventilator-associated complication." This was compared with 89 of 229 (39%) diagnosed as clinical ventilator-associated infection (Kappa = 0.068). Ten of 15 subjects identified as ventilator-associated condition did not meet criteria for infection-related ventilator-associated complication primarily because they did not receive 4 days of antibiotics. Ventilator-associated condition subjects were similar demographically to nonventilator-associated condition subjects and had similar mortality (13% vs 10%), PICU-free days (6.9 ± 7.7; interquartile range, 0-14 vs 9.8 ± 9.6; interquartile range, 0-19; p = 0.25), but fewer ventilator-free days (6.6 ± 9.3; interquartile range, 1-15 vs 12.4 ± 10.7; interquartile range, 0-22; p = 0.04). The clinical ventilator-associated infection diagnosis in the ventilator-associated infection study was associated with fewer PICU-free days but no difference in mortality or ventilator-free days. CONCLUSIONS: The ventilator-associated event criteria appear to be insensitive to the clinical diagnosis of ventilator-associated infection. Differentiation between ventilator-associated condition and infection-related ventilator-associated complication was primarily determined by the clinician decision to treat with antibiotics rather than clinical signs and symptoms. The utility of the proposed pediatric ventilator-associated event criteria as a surrogate for ventilator-associated infection criteria is unclear.

Low serum albumin levels prior to pediatric allogeneic HCT are associated with increased need for critical care interventions and increased 6-month mortality.

Poor nutritional status in HCT patients is a negative prognostic factor. There are no pediatric studies evaluating albumin levels prior to HCT and need for critical care interventions. We hypothesized that pediatric patients with low albumin levels, routinely measured 30 days (±10 days) prior to allogeneic HCT, have a higher risk of critical care interventions in the post-transplant period. We performed a 5-year retrospective study of pediatric patients who underwent allogeneic HCT for any indication. Patients were categorized based on albumin level. Hypoalbuminemia was defined as <3.1 g/dL. A total of 73 patients were included, with a median age of 7.4 years (IQR 3.3, 13.2). Patients with hypoalbuminemia had higher needs for critical care interventions including non-invasive ventilation (44% vs 8%, P=.01), mechanical ventilation (67% vs 17%, P<.01), and vasoactive therapy (56% vs 16%, P=.01). Patients with hypoalbuminemia also had a higher 6-month mortality (56% vs 17%, P=.02). Our data demonstrate that children undergoing allogeneic HCT with hypoalbuminemia in the pretransplant period are more likely to require critical care interventions and have higher 6-month mortality. These findings identify an at-risk population in which nutritional improvements may be instituted prior to HCT in hopes of improving outcomes.

An Evaluation of Various Ventilator-Associated Infection Criteria in a PICU.

OBJECTIVE: To describe characteristics and overlap associated with various ventilator-associated infection criteria in the PICU. DESIGN: Retrospective observational study. SETTING: A quaternary care children's hospital PICU. PATIENTS: Children ventilated more than 48 hours, excluding patients with tracheostomy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ventilator-associated infection, including pneumonia, infection-related ventilator-associated condition, tracheobronchitis, and lower respiratory tract infection were defined according to criteria from the Centers for Disease Control and Prevention or medical literature. Clinical data were abstracted to assign diagnoses of each ventilator-associated infection. In 300 episodes of mechanical ventilation, there were 30 individual episodes of ventilator-associated infection. Nine episodes met more than one definition. Rates per 1,000 ventilator days were 2.60 for ventilator-associated pneumonia, 2.16 for infection-related ventilator-associated condition, 5.19 for ventilator-associated tracheobronchitis, and 6.92 for lower respiratory tract infection. The rate of any ventilator-associated infection was 12.98 per 1,000 ventilator days. Individual criteria had similar risk factors and outcomes. Risk factors for development of any ventilator-associated infection included older age (p = 0.003) and trauma (p = 0.007), while less cardiac surgery patients developed ventilator-associated infection (p = 0.015). On multivariate analysis, trauma was the only independent risk factor (adjusted odds ratio, 3.10; 95% CI, 1.15-8.38). Developing any ventilator-associated infection was associated with longer duration of mechanical ventilation (p < 0.001) and longer PICU length of stay (p < 0.001) but not PICU mortality (p = 0.523). CONCLUSIONS: There is little overlap in diagnosis of various ventilator-associated infection. However, the risk factors and outcomes associated with individual criteria are similar, indicating that they may have validity in identifying true pathology. Ventilator-associated infection in general is likely a larger problem than indicated by low hospital-reported rates of ventilator-associated pneumonia. There is clinical confusion due to the presence of several diagnostic criteria for ventilator-associated infection. Developing a more inclusive and clinically relevant criterion for diagnosing ventilator-associated infection is warranted to accurately assess their impact and improve guidance for clinicians in evaluating and treating ventilator-associated infection.

Acute Vilazodone Toxicity in a Pediatric Patient.

BACKGROUND: Vilazodone is a selective serotonin reuptake inhibitor and 5HT1A agonist recently approved to treat depression in adults. To date, there are minimal data available regarding the expected course and treatment of acute vilazodone ingestions. CASE REPORT: We report a case of a previously healthy 19-month-old girl who presented after an acute ingestion of an estimated 37 mg/kg vilazodone. She was taken to an outside emergency department approximately 1 h after an unwitnessed ingestion. Initially, the patient was noted to have decreased responsiveness, sluggish but reactive pupils, altered mental status, and reported seizure activity. She was given intravenous lorazepam for seizure control, intubated, and transferred to a pediatric tertiary care facility, where she continued to show signs of serotonin toxicity and received treatment with benzodiazepines and cyproheptadine. Despite vilazodone's long half-life and the large amount ingested, the patient was extubated within 10 h of presentation, had returned to baseline mental status by 22 h, and was discharged home approximately 57 h after ingestion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Accidental ingestions are common in the pediatric population. Emergency physicians need to be aware of the signs and symptoms of acute medication toxicities, the expected clinical course, and the necessary supportive measures used to treat these patients. Because vilazodone is a recently approved medication, there is little experience with acute vilazodone ingestions. This report considerably increases the understanding of vilazodone's effects in the setting of an acute ingestion.

Devastating Ischemic Stroke Following Selective Arterial Embolization of a Large Chest Wall Aneurysmal Bone Cyst.

Aneurysmal bone cysts (ABC) are benign bone lesions found in children and young adults. Rarely, these lesions can arise from ribs, and there is disagreement on the best treatment because of proximity to vital structures. Frequently, surgeons remove ABC with en bloc resection. Selective arterial embolization has been used as an adjunct to surgery, or rarely as the primary treatment. We report a case of embolic stroke complicating embolization of a rib ABC, likely from the presence of collateral circulation between the mass and vertebral artery. Caution should be taken when performing embolization of lesions in this location because of potential complications.

Alteplase use for malfunctioning central venous catheters correlates with catheter-associated bloodstream infections.

OBJECTIVES: A catheter thrombosis and the presence of a catheter-associated bloodstream infection (CBSI) often occur simultaneously, but it is unclear if or to what degree the two complications relate. Several animal and adult studies indicate a relationship between fibrin sheaths and thrombi in the development of CBSIs. To date, there has been limited human investigation in the pediatric population to determine a clear link between the presence of a thrombus and bacteremia. The use of alteplase for malfunctioning central venous catheter may indicate the formation of intraluminal thrombus or fibrin sheath. A catheter that requires alteplase is at higher risk of a CBSI. DESIGN: A retrospective chart review from July 2008 to December 2010. SETTING: PICU. PATIENTS: All patients with central catheters admitted to the PICU. INTERVENTIONS: No interventions performed with the retrospective study. MEASUREMENTS: Number of total central venous catheters, number of central venous catheters that received treatment with alteplase, and number of CBSIs. MAIN RESULTS: Preliminary data during the study period identified 3,289 central venous catheters. Twelve percent of these catheters required at least one dose of alteplase. There were 40 CBSIs during this same time period of which 28% received alteplase during the 5 days preceding the positive blood culture. The odds ratio for getting a CBSI when alteplase is administered is 2.87 (confidence interval 1.42-5.80; p = 0.002). The average age of the central venous catheters at time of infection was not statistically different, 16.1 days in the alteplase catheters compared with 25.6 days for the catheters that did not receive alteplase (p = 0.6). CONCLUSIONS: There is a positive correlation between the use of alteplase for malfunctioning central venous catheters and the development of a CASBI. This is likely associated with the presence of an intraluminal fibrin sheath or thrombus. This study adds evidence linking thrombus formation to CBSI.

A conserved sequence in caveolin-1 is both necessary and sufficient for caveolin polarity and cell directional migration.

Caveolin-1 (Cav-1) plays an important role in the organization of signaling molecules involved in a variety of signaling pathways, including those mediating cell motility. Here we show that amino acids K47-K57 of Cav-1 are a highly conserved sequence in Cav-1 and Cav-3 proteins, and that expression of either K47-K57 deletion Cav-1 mutant or wild-type Cav-2 that lacks this sequence exhibits a non-polarized distribution pattern. Expression of K47-K57 in Cav-2 leads to Cav-2 polarity, suggesting that expression of K47-K57 is sufficient to direct caveolin polarity. Importantly, we show that expression of this sequence is both necessary and sufficient to promote cell directional migration. Thus, our results support the conclusion that Cav-1 polarity is critical for cell directional migration.