Multisite Veno-Venous Cannulation for Neonates and Nonambulatory Children.

OBJECTIVES: Neonates with respiratory failure are ideally supported with veno-venous rather than veno-arterial extracorporeal membrane oxygenation due to the reduced rate of neurologic complications. However, the proportion of neonates supported with veno-venous extracorporeal membrane oxygenation is declining. We report multisite veno-venous extracorporeal membrane oxygenation, accessing the neck, returning to the inferior vena cava via the common femoral vein in neonates and children less than 10 kg. DESIGN: Retrospective case series with 1 year minimum follow-up. PATIENTS: Patients less than 10 kg supported with veno-venous extracorporeal membrane oxygenation accessing the jugular and returning to the femoral vein. SETTING: A 30-bed pediatric intensive care delivering extracorporeal membrane oxygenation to approximately 20 children annually. INTERVENTIONS: Veno-venous extracorporeal membrane oxygenation accessing the jugular and returning to the femoral vein was delivered using two single lumen cannulae. MEASUREMENTS AND MAIN RESULTS: January 2015 to August 2019, 11 patients underwent veno-venous extracorporeal membrane oxygenation accessing the jugular and returning to the femoral vein with median weight of 3.6 kg (interquartile range 2.8-6.1 kg), and median corrected gestational age of 13 days (interquartile range, 2-175 d). The smallest patient weighed 2.1 kg. Seven patients had comorbidities. Extracorporeal membrane oxygenation was technically successful in all patients with median flows of 126 mL/kg/min (interquartile range, 120-138 mL/kg/min) and median arterial oxygenation saturation of 94% (interquartile range, 91-98%) at 24 hours. Nine survived to home discharge, and two were palliated. Common femoral vein occlusion was observed in all patients on ultrasound post decannulation. There was no clinical or functional deficit in the cannulated limb at follow-up, a minimum of 1 year post extracorporeal membrane oxygenation. CONCLUSIONS: Veno-venous extracorporeal membrane oxygenation accessing the jugular and returning to the femoral vein was performed safely in patients under 10 kg with the smallest patient weighing 2.1 kg. Although occlusion of the common femoral vein was observed in patients post decannulation, subsequent follow-up demonstrated no clinical implications. We challenge current practice that veno-venous extracorporeal membrane oxygenation accessing the jugular and returning to the femoral vein cannot be performed in nonambulatory patients and suggest that this strategy is preferred over veno-arterial extracorporeal membrane oxygenation in infants requiring extracorporeal membrane oxygenation for respiratory failure.

Association Between Treatments and Short-Term Biochemical Improvements and Clinical Outcomes in Post-Severe Acute Respiratory Syndrome Coronavirus-2 Inflammatory Syndrome.

OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs. DESIGN: Multicenter observational study. SETTING: Twenty-one U.K. PICUs. PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally recommended. CONCLUSIONS: We were unable to identify any short-term benefit from any of the treatments, or treatment combinations, administered. Despite a lack of evidence, treatment guidelines for multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 have become very similar in advising step-wise treatments. Retaining clinical equipoise regarding treatment will allow clinicians to enroll children in robust clinical trials to determine the optimal treatment for this novel important condition.

Postnatal impact of a prenatally diagnosed double aortic arch.

BACKGROUND: A double aortic arch (DAA) is increasingly identified before birth; however, there are no published data describing the postnatal outcome of a large prenatal cohort. OBJECTIVE: To describe the associations, symptoms and impact of prenatally diagnosed DAA. METHODS: Retrospective review of consecutive cases seen at two fetal cardiology units from 2014 to 2019. Clinical records including symptoms and assessment of tracheobronchial compression using flexible bronchoscopy were reviewed. Moderate-severe tracheal compression was defined as >75% occlusion of the lumen. RESULTS: There were 50 cases identified prenatally and 48 with postnatal follow-up. Array comparative genomic hybridisation (aCGH) was abnormal in 2/50 (4%), aCGH was normal in 33/50 (66%) and of those reviewed after birth, 13 were phenotypically normal. After birth, there was a complete DAA with patency of both arches in 8/48 (17%) and in 40/48 (83%) there was a segment of the left arch which was a non-patent, ligamentous connection.Stridor was present in 6/48 (13%) on the day of birth. Tracheo-oesophageal compressive symptoms/signs were present in 31/48 (65%) patients at median age of 59 days (IQR 9-182 days). Tracheal/carinal compression was present in 40/45 (88%) cases. Seven of 17 (41%) asymptomatic cases demonstrated moderate-severe tracheal compression. All morphologies of DAA caused symptoms and morphology type was not predictive of significant tracheal compression (p=0.3). CONCLUSIONS: Genetic testing should be offered following detection of double aortic arch. Early signs of tracheal compression are common and therefore delivery where onsite neonatal support is available is recommended. Significant tracheal compression may be present even in the absence of symptoms.

Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study.

BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85-1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 µg/L to 757 µg/L), whereas the lymphocyte count increased to more than 1·0 × 109 cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.

Biodegradable Stents for the Relief of Vascular Bronchial Compression in Children With Left Atrial Enlargement.

BACKGROUND: We report our experience of the biodegradable polydioxanone stent in cases of bronchial compression by a dilated left atrium in children with heart disease. METHODS: Eight custom-made biodegradable stents were inserted into the left main bronchus in 5 patients diagnosed with critical airway compression. Four of the 5 patients were ventilator-dependent with significant cardiac morbidity. RESULTS: Stents were inserted without complication under fluoroscopic guidance. All experienced improvement in symptoms over time. In 3 patients, repeat bronchial stenting was performed where stent degradation was associated with recurrence of vascular airway compression and symptoms. No stents migrated nor was there evidence of bronchial or vascular erosion. There was 1 death, unrelated to the stent, and all remaining survivors were well at a 2-year follow-up. CONCLUSION: The use of the polydioxanone biodegradable stent appeared safe in this cohort of critically ill patients with vascular bronchial compression. There use may aid weaning from mechanical ventilation and support eventual cardiac recovery.

Management of severe bronchiolitis: impact of NICE guidelines.

OBJECTIVE: To understand the impact of the National Institute for Health and Care Excellence (NICE) bronchiolitis guidelines on the management of children referred to paediatric intensive care unit (PICU) with bronchiolitis. DESIGN AND SETTING: Data were collected on all children referred to a regional PICU transport service with the clinical diagnosis of bronchiolitis during the winter prior to the NICE consultation period (2011-2012) and during the winter after publication (2015-2016). Management initiated by the referring hospital was assessed. RESULTS: There were 165 infants referred with bronchiolitis in epoch 1 and 187 in epoch 2. Nebuliser use increased from 28% in epoch 1 to 53% in epoch 2. Increased use of high-flow nasal cannula oxygen and reduction in continuous positive airway pressure use were observed. The use of antibiotics did not change between epochs. CONCLUSION: The use of nebulised therapies has increased in the management of severe bronchiolitis despite national guidance to the contrary.

Learning From Investigation After Death.

OBJECTIVES: The acceptability of traditional postmortem examination to bereaved families, coupled with a misguided professional view about their limited utility, has led to decrease in this ultimate investigation. Research recurrently demonstrates that postmortem examination provides clinically relevant information despite ever-improving diagnostic techniques. This review examines postmortem examination for children who die in PICU-whether consented or nonconsented (legally mandated). It explores how such investigations might provide useful information and suggests that PICU and pathology teams work together to provide information for bereaved families to either enable them to consent to postmortem interventions or understand necessary forensic processes. Newer technologies such as postmortem imaging and laparoscope-assisted/ultrasound-guided tissue sampling are reviewed, with the hope that greater acceptability to families may lead to a welcome resurgence in postmortem information for clinicians, tempered by realization that widespread acceptance of their equivalence to standard techniques by most forensic services is awaited. DATA SOURCES: Literature review. STUDY SELECTION: Journal articles describing practices in pediatric and adult postmortem examination. DATA EXTRACTION: Not available. DATA SYNTHESIS: Not available. CONCLUSIONS: The PICU team have a duty to help bereaved parents understand what postmortem investigations are available, or might be mandated, after the death of their child. A thoughtful, unhurried, and compassionate discussion should be arranged with expert pathology teams and any specialists who have cared for the child to explain how investigations can provide information about what is involved-including availability and suitability of newer techniques. This should include information about when a child's body, organs, or tissues will be available for the funeral, necessary legal procedures and how and when results will be explained to them.

Critical airway obstruction in apparently asymptomatic neonates.

Central airway obstruction (trachea and major bronchi) in neonates can be caused by malacia, stenosis, or compression by masses or vascular structures. These abnormalities may be present in the neonatal period but are typically not detected until at least 6 months of age. We present four patients (1.6-4.1 kg, 32-41 weeks gestation) with nonspecific symptoms (e.g., poor weight gain, difficulty weaning from CPAP) who underwent bronchoscopy in the neonatal period. Critical airway obstruction (>90%) was identified in these relatively asymptomatic neonates. We suggest a low threshold for investigation with bronchoscopy in high-risk neonates. Pediatr Pulmonol. 2017;52:E15-E17. © 2016 Wiley Periodicals, Inc.

Intravenous magnesium sulfate for treating children with acute asthma in the emergency department.

BACKGROUND: Acute asthma in children can be life-threatening and must be treated promptly in the emergency setting. Intravenous magnesium sulfate is recommended by various guidelines for cases of acute asthma that have not responded to first-line treatment with bronchodilators and steroids. The treatment has recently been shown to reduce the need for hospital admission for adults compared with placebo, but it is unclear whether it is equally effective for children. OBJECTIVES: To assess the safety and efficacy of intravenous magnesium sulfate (IV MgSO4) in children treated for acute asthma in the emergency department (ED). SEARCH METHODS: We identified studies by searching the Cochrane Airways Review Group Specialised Register up to 23 February 2016. We also searched ClinicalTrials.gov and reference lists of other reviews, and we contacted study authors to ask for additional information. SELECTION CRITERIA: We included randomised controlled trials of children treated in the ED for exacerbations of asthma if they compared any dose of IV MgSO4 with placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened the results of the search and independently extracted data from studies meeting the inclusion criteria. We resolved disagreements through discussion and contacted study authors in cases of missing data and other uncertainties relating to the studies.We analysed dichotomous data as odds ratios and continuous data as mean differences, both using fixed-effect models. We assessed each study for risk of bias and rated the quality of evidence for each outcome with GRADE and presented the results in a 'Summary of findings' table. There was insufficient evidence to conduct the planned subgroup analyses. MAIN RESULTS: Five studies (182 children) met the inclusion criteria, and four contributed data to at least one meta-analysis. The included studies were overall at low risk of bias, but our confidence in the evidence was generally low, mainly due to the small sample sizes. Treatment with IV MgSO4 reduced the odds of admission to hospital by 68% (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.74; children = 115; studies = 3; I(2) = 63%). This result was based on data from just three studies including 115 children. Meta-analysis for the secondary outcomes was extremely limited by paucity of data. We performed meta-analysis for the outcome 'return to the emergency department within 48 hours', which showed a very imprecise effect estimate that was not statistically significant (OR 0.40, 95% CI 0.02 to 10.30; children = 85; studies = 2; I(2) = 0%). Side effects and adverse events were not consistently reported and meta-analysis was not possible, however few side effects or adverse events were reported. AUTHORS' CONCLUSIONS: IV MgSO4 may reduce the need for hospital admission in children presenting to the ED with moderate to severe exacerbations of asthma, but the evidence is extremely limited by the number and size of studies. Few side effects of the treatment were reported, but the data were extremely limited.

Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children.

BACKGROUND: There are several treatment options for managing acute asthma exacerbations (sustained worsening of symptoms that do not subside with regular treatment and require a change in management). Guidelines advocate the use of inhaled short acting beta2-agonists (SABAs) in children experiencing an asthma exacerbation. Anticholinergic agents, such as ipratropium bromide and atropine sulfate, have a slower onset of action and weaker bronchodilating effect, but may specifically relieve cholinergic bronchomotor tone and decrease mucosal edema and secretions. Therefore, the combination of inhaled anticholinergics with SABAs may yield enhanced and prolonged bronchodilation. OBJECTIVES: To determine whether the addition of inhaled anticholinergics to SABAs provides clinical improvement and affects the incidence of adverse effects in children with acute asthma exacerbations. SEARCH METHODS: We searched MEDLINE (1966 to April 2000), EMBASE (1980 to April 2000), CINAHL (1982 to April 2000) and reference lists of studies of previous versions of this review. We also contacted drug manufacturers and trialists. For the 2012 review update, we undertook an 'all years' search of the Cochrane Airways Group's register on the 18 April 2012. SELECTION CRITERIA: Randomized parallel trials comparing the combination of inhaled anticholinergics and SABAs with SABAs alone in children (aged 18 months to 18 years) with an acute asthma exacerbation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used the GRADE rating system to assess the quality of evidence for our primary outcome (hospital admission). MAIN RESULTS: Twenty trials met the review eligibility criteria, generated 24 study comparisons and comprised 2697 randomised children aged one to 18 years, presenting predominantly with moderate or severe exacerbations. Most studies involved both preschool-aged children and school-aged children; three studies also included a small proportion of infants less than 18 months of age. Nine trials (45%) were at a low risk of bias. Most trials used a fixed-dose protocol of three doses of 250 mcg or two doses of 500 mcg of nebulized ipratropium bromide in combination with a SABA over 30 to 90 minutes while three trials used a single dose and two used a flexible-dose protocol according to the need for SABA.The addition of an anticholinergic to a SABA significantly reduced the risk of hospital admission (risk ratio (RR) 0.73; 95% confidence interval (CI) 0.63 to 0.85; 15 studies, 2497 children, high-quality evidence). In the group receiving only SABAs, 23 out of 100 children with acute asthma were admitted to hospital compared with 17 (95% CI 15 to 20) out of 100 children treated with SABAs plus anticholinergics. This represents an overall number needed to treat for an additional beneficial outcome (NNTB) of 16 (95% CI 12 to 29).Trends towards a greater effect with increased treatment intensity and with increased asthma severity were observed, but did not reach statistical significance. There was no effect modification due to concomitant use of oral corticosteroids and the effect of age could not be explored. However, exclusion of the one trial that included infants (< 18 months) and contributed data to the main outcome, did not affect the results. Statistically significant group differences favoring anticholinergic use were observed for lung function, clinical score at 120 minutes, oxygen saturation at 60 minutes, and the need for repeat use of bronchodilators prior to discharge from the emergency department. No significant group difference was seen in relapse rates.Fewer children treated with anticholinergics plus SABA reported nausea and tremor compared with SABA alone; no significant group difference was observed for vomiting. AUTHORS' CONCLUSIONS: Children with an asthma exacerbation experience a lower risk of admission to hospital if they are treated with the combination of inhaled SABAs plus anticholinergic versus SABA alone. They also experience a greater improvement in lung function and less risk of nausea and tremor. Within this group, the findings suggested, but did not prove, the possibility of an effect modification, where intensity of anticholinergic treatment and asthma severity, could be associated with greater benefit.Further research is required to identify the characteristics of children that may benefit from anticholinergic use (e.g. age and asthma severity including mild exacerbation and impending respiratory failure) and the treatment modalities (dose, intensity, and duration) associated with most benefit from anticholinergic use better.

Fluticasone at different doses for chronic asthma in adults and children.

BACKGROUND: Inhaled fluticasone propionate (FP) is a high-potency inhaled corticosteroid used in the treatment of asthma. OBJECTIVES: 1. To assess the efficacy and safety outcomes of inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma.2. To test for the presence of a dose-response effect. SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register (January 2008). SELECTION CRITERIA: Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: One review author extracted data. These were checked and verified by a second reviewer. Quantitative analyses where undertaken using Review Manager. MAIN RESULTS: Fifty-one published and unpublished trials (representing 55 group comparisons, 10,797 participants) met the inclusion criteria. In asthmatics with mild to moderate disease who were not on oral steroids, FP did not exhibit a dose-response effect in the lower dose comparisons in FEV1 (50mcg, 100mcg, 200mcg and 4-500mcg daily). There were no statisitically significant differences between 4-500mcg and 800-1000mcg, and between 50-100 and 800-1000mcg of FP. When 200mcg was compared with 800-1000mcg daily FEV1 favoured the four/five fold increase. For PEF, a dose response was present with FP when low and moderate, and low and high doses of FP were compared. There was no evidence of a dose-response effect on symptoms or rescue beta-2 agonist use. The likelihood of hoarseness and oral candidiasis was significantly greater for the higher doses (800 to 1000 microg/day). People with oral steroid-dependent asthma treated with FP (2000 microg/day) were significantly more likely to reduce oral prednisolone than those on 1000 to 1500 microg/day (Peto odds Ratio 2.8, 95% CI 1.3 to 6.3). The highest dose also allowed a significant reduction in daily oral prednisolone dose compared to 1000 to 1500 microg/day (WMD 2.0 mg/day, 95% CI 0.1 to 4.0 mg/day). AUTHORS' CONCLUSIONS: We have not found evidence of a pronounced dose response in FEV1 with increasing doses of fluticasone. The number of studies contributing to our primary outcomes was low. At dose ratios of 1:2, there are statistically significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 microg/day) as they do on high doses (800 to 1000 microg/day). More work in severe asthma would help to confirm that doses of FP above 500 microg/day confer greater benefit in this subgroup than doses of around 200 microg/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 microg/day.