Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.

Ethnicity and Observed Oxygen Saturations, Fraction of Inspired Oxygen, and Clinical Outcomes: A Post-Hoc Analysis of the Oxy-PICU Trial of Conservative Oxygenation.

OBJECTIVES: A conservative oxygenation strategy, targeting peripheral oxygen saturations (Sp o2 ) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Sp o2 greater than 94% in our recent Oxy-PICU trial. Sp o2 monitors may overestimate arterial oxygen saturation (Sa o2 ) in patients with higher levels of skin pigmentation compared with those with less skin pigmentation. We investigated if ethnicity was associated with changes in distributions of Sp o2 and F io2 and outcome. DESIGN: Post-hoc analysis of a pragmatic, open-label, multicenter randomized controlled trial. SETTING: Fifteen PICUs across the United Kingdom and Scotland. PATIENTS: Children aged 38 weeks corrected gestational age to 15 years accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. METHODS: Hierarchical regression models for Sp o2 and F io2 , and ordinal models for the primary trial outcome of a composite of the duration of organ support at 30 days and death, were used to examine the effects of ethnicity, accounting for baseline Sp o2 , F io2 , and mean airway pressure and trial allocation. MEASUREMENTS AND MAIN RESULTS: Ethnicity data were available for 1577 of 1986 eligible children, 1408 (89.3%) of which were White, Asian, or Black. Sp o2 and F io2 distributions did not vary according to Black or Asian ethnicity compared with White children. The trial primary outcome measure also did not vary significantly with ethnicity. The point estimate for the treatment effect of conservative oxygenation in Black children was 0.64 (95% CI, 0.33-1.25) compared with 0.84 (0.68-1.04) in the overall trial population. CONCLUSIONS: These data do not suggest that the association between improved outcomes and conservative oxygenation strategy in mechanically ventilated children in PICU is modified by ethnicity.

A Bedside Equation to Estimate Endotracheal Tube Length for Infants.

OBJECTIVE: To develop a bedside equation that can be used to estimate the ideal oral and nasal endotracheal tube (ETT) length for children younger than 1 year of age. STUDY DESIGN: Retrospective database analysis of 735 children younger than 1 year of age admitted to pediatric intensive care at Evelina London Children's Hospital from June 1, 2019, through August 31, 2021. ETT positions were determined by tube-tip superimposition over vertebral body on postintubation chest radiograph by trained medical students and pediatric radiologists with bedside assessment of ETT length at nostril or lip as recorded electronically by nursing staff. RESULTS: The position of 1176 ETTs were evaluated, of which 784 (66%) were nasal and 392 (33%) were oral. After averaging length to account for multiple intubation events per patient, 281 (39%) nasal tubes and 105 (28%) oral tubes were found to be positioned optimally at T2. Using weight was superior to age or corrected age at estimating ETT length. Regression analysis revealed that optimal (T2) positioning of oral ETTs occurs at a length of (weight2+8) cm and in nasal ETTs at (weight2+9.5) cm with a mean absolute prediction error of 5%. The formulae did not require adjustments for those with comorbidities or prematurity. CONCLUSIONS: The optimal insertion length of ETTs placed both orally and nasally in children up to 1 year of age can be estimated with appropriate accuracy by a simple bedside formula using weight as the only variable.

Variation in Early Pediatric Intensive Care Management Strategies and Duration of Invasive Mechanical Ventilation for Acute Viral Bronchiolitis in the United Kingdom: A Retrospective Multicenter Cohort Study.

OBJECTIVES: Management of mechanically ventilated patients with bronchiolitis is not standardized and duration of mechanical ventilation has been shown to vary widely between centers. The aim of this study was to examine practice in a large number of U.K. PICUs with a view to identify if early management choices relating to fluid prescription, sedative agent use, and endotracheal tube (ETT) placement were associated with differences in duration of invasive mechanical ventilation (IMV). DESIGN: Retrospective multicenter cohort study. Primary outcome was duration of IMV. A hierarchical gamma generalized linear model was used to test for associations between practice variables (sedative and neuromuscular blocking agents, route of endotracheal intubation at 24 hr and fluid balance at 48 hr) and duration of IMV after adjustment for known confounders. SETTING: Thirteen U.K. PICUs. Duration of 2 months between November and December 2019. PATIENTS: Three hundred fifty infants receiving IMV for bronchiolitis. Excluded were patients receiving long-term ventilation, extracorporeal life support, or who died before separation from IMV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjustment for confounders, several variables were associated with an increase in the geometric mean duration of IMV (expressed as a percentage) including: nasal ETT use, 16% (95% CI, 1-32%); neuromuscular blockade use, 39% (95% CI, 21-61%); and fluid balance at 48 hr, 13% per 100 mL/kg positive fluid balance (95% CI, -1% to 28%). The association of sedative use varied with class of agent. The use of an alpha-2 agonist alone was associated with a reduction in duration of IMV by 19% in relation to no sedative agent (95% CI, -31 to -5%), whereas benzodiazepine uses alone or with alpha-2 agonist in combination were similar to using neither agent. CONCLUSIONS: Early management strategies for bronchiolitis were associated with the duration of IMV across U.K. centers after adjustment for confounders. Future work should prospectively assess the impact of fluid restriction, route of endotracheal intubation, and alpha-2 agonist use on duration of IMV in infants with bronchiolitis, with the aim of reducing seasonal bed pressure.

Catheter directed thrombolysis for a pulmonary arterial thrombus on VA ECMO in a child - a case report.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) as a bridge to cardiac transplantation is considered a high risk support strategy in the paediatric population. METHODS: We describe the case of a 12 year old boy who required V-A ECMO support for rapidly deteriorating cardiomyopathy and developed a massive pulmonary embolus (PE) peri-cannulation. Subsequent investigations were also positive for heparin induced thrombocytopenia. RESULTS: We elected to treat the PE with ultrasound accelerated catheter directed thrombolysis using the advantages of this minimally invasive targeted method to try and resolve the PE and avoid a cerebral haemorrhage, both of which would have taken the patient off the urgent transplant list. CONCLUSION: The PE resolved in 24 h and he went on to receive a cardiac transplant and have a favourable outcome.

Fifteen-minute consultation: When to consider extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a form of organ support which is used for severe, potentially reversible respiratory, cardiac or cardiorespiratory failure. While it is associated with significant risk of intracerebral injury in neonates and children, outcomes can be excellent, and timely referral is associated with improved survival and reduced morbidity. This article provides a concise summary of the technical aspects of ECMO support, indications for referral, complications, outcomes and important considerations for follow-up.

Invasive Mechanical Ventilation for Acute Viral Bronchiolitis: Retrospective Multicenter Cohort Study.

OBJECTIVES: Bronchiolitis is a leading cause of PICU admission and a major contributor to resource utilization during the winter season. Management in mechanically ventilated patients with bronchiolitis is not standardized. We aimed to assess whether variations exist in management between the centers and then to assess if differences in PICU outcomes are found. DESIGN: Retrospective cohort study. SETTING: Three tertiary PICUs (Centers A, B, and C) in London, United Kingdom. PATIENTS: Patients under 1 year of age (n = 462) who received invasive mechanical ventilation for acute viral bronchiolitis from 2012-2016. INTERVENTIONS: None. DESIGN: Retrospective cohort study. MEASUREMENTS AND MAIN RESULTS: Data collected include all sedative agents administered, 48 hour cumulative fluid balance and location of endotracheal tube (oral or nasal). Primary outcome was duration of invasive mechanical ventilation. A generalized linear model was used to test for differences in duration of invasive mechanical ventilation between centers after adjustment for confounders: corrected gestational age, oxygen saturation index, bacterial coinfection, prematurity, respiratory syncytial virus status, risk of mortality score and comorbidity. Baseline characteristics were similar, other than a higher risk of mortality score at center A and higher admission oxygen saturation index at center C. Center A was associated with utilization of the most benzodiazepine and opiate sedation, the fewest nasal endotracheal tubes, and the highest mean cumulative fluid balance at 48 hours.Center A had an adjusted mean duration of invasive mechanical ventilation that was 44% longer than center C (95% CI, 25-66%; p < 0.001).The majority of confounders had an association with the duration of invasive mechanical ventilation; all were biologically plausible. Corrected gestational age was negatively associated with the duration of invasive mechanical ventilation for preterm infants less than 32 weeks, but not for term or 32-37 week infants (interaction effect). This meant that at a corrected age of 0 months, a less than 32-week infant had a mean duration that was 55% greater than a term infant: this effect had disappeared by 8 months old. CONCLUSIONS: Between-center variations exist in both practices and outcomes. The relationship between these two findings could be further tested through implementation science with "optimal care bundles."

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.

Early Use of Adjunctive Therapies for Pediatric Acute Respiratory Distress Syndrome: A PARDIE Study.

Rationale: Few data exist to guide early adjunctive therapy use in pediatric acute respiratory distress syndrome (PARDS).Objectives: To describe contemporary use of adjunctive therapies for early PARDS as a framework for future investigations.Methods: This was a preplanned substudy of a prospective, international, cross-sectional observational study of children with PARDS from 100 centers over 10 study weeks.Measurements and Main Results: We investigated six adjunctive therapies for PARDS: continuous neuromuscular blockade, corticosteroids, inhaled nitric oxide (iNO), prone positioning, high-frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation. Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index of each therapy; corticosteroids started at the lowest oxygenation index (13.0; interquartile range, 7.6-22.0) and HFOV at the highest (25.7; interquartile range, 16.7-37.3). Continuous neuromuscular blockade was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and extracorporeal membrane oxygenation (3%). Steroids, iNO, and HFOV were associated with comorbidities. Prone positioning and HFOV were more common in middle-income countries and less frequently used in North America. The use of multiple ancillary therapies increased over the first 3 days of PARDS, but there was not an easily identifiable pattern of combination or order of use.Conclusions: The contemporary description of prevalence, combinations of therapies, and oxygenation threshold for which the therapies are applied is important for design of future studies. Region of the world, income, and comorbidities influence adjunctive therapy use and are important variables to include in PARDS investigations.

Acute Kidney Injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Experience From PICUs Across United Kingdom.

OBJECTIVES: To study the prevalence, evolution, and clinical factors associated with acute kidney injury in children admitted to PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. DESIGN: Multicenter observational study. SETTING: Fifteen PICUs across the United Kingdom. PATIENTS: Patients admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 between March 14, 2020, and May 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deidentified data collected as part of routine clinical care were analyzed. All children were diagnosed and staged for acute kidney injury based on the level of serum creatinine above the upper limit of reference interval values according to published guidance. Severe acute kidney injury was defined as stage 2/3 acute kidney injury. Uni- and multivariable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe acute kidney injury. Over the study period, 116 patients with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 were admitted to 15 United Kingdom PICUs. Any-stage acute kidney injury occurred in 48 of 116 patients (41.4%) and severe acute kidney injury in 32 of 116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein, Pediatric Index of Mortality 3 score, vasoactive medication, and invasive mechanical ventilation were associated with severe acute kidney injury. In multivariable logistic regression, hyperferritinemia was associated with severe acute kidney injury (compared with nonsevere acute kidney injury; adjusted odds ratio 1.04; 95% CI, 1.01-1.08; p = 0.04). Severe acute kidney injury was associated with longer PICU stay (median 5 days [interquartile range, 4-7 d] vs 3 days [interquartile range, 1.5-5 d]; p < 0.001) and increased duration of invasive mechanical ventilation (median 4 days [interquartile range, 2-6 d] vs 2 days [interquartile range, 1-3 d]; p = 0.04). CONCLUSIONS: Severe acute kidney injury occurred in just over a quarter of children admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Hyperferritinemia was significantly associated with severe acute kidney injury. Severe acute kidney injury was associated with increased duration of stay and ventilation. Although short-term outcomes for acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 appear good, long-term outcomes are unknown.

Factors Behind Decline of Venovenous Extracorporeal Membrane Oxygenation to Support Neonatal Respiratory Failure.

OBJECTIVES: Neonates with respiratory failure are ideally supported with venovenous rather than venoarterial extracorporeal membrane oxygenation due to the reduced rate of neurologic complications. However, the proportion of neonates supported with venovenous extracorporeal membrane oxygenation is declining. We aimed to explore the factors behind this decline. DESIGN: We conducted a survey in order to understand current practice across the United Kingdom, exploring barriers to neonatal venovenous extracorporeal membrane oxygenation in addition to collecting U.K.-wide retrospective data from 2000 onwards. PATIENTS: Neonates with respiratory failure supported with extracorporeal membrane oxygenation in the United Kingdom. SETTING: All 11 pediatric U.K. extracorporeal membrane oxygenation centers provided data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The percentage of neonates with respiratory failure supported with venovenous extracorporeal membrane oxygenation has declined from 58% to 16% over the last decade, reflected internationally with a decrease of 1.3% per year. Nine extracorporeal membrane oxygenation centers are able to offer pediatric venovenous extracorporeal membrane oxygenation, but only four offer neonatal venovenous extracorporeal membrane oxygenation. Of those able to provide neonatal venovenous extracorporeal membrane oxygenation, three centers use dual lumen cannulae and one uses neonatal multisite cannulation. The most frequently cited barriers to neonatal venovenous extracorporeal membrane oxygenation were the lack of availability of a suitable dual lumen cannula with concerns of cardiac perforation and challenges of multisite cannulation due to small caliber femoral veins. CONCLUSIONS: The majority of U.K. centers are unable to provide venovenous extracorporeal membrane oxygenation for neonates due to concerns with availability and suitability of dual lumen cannulae. An alternative to be considered is the use of multisite cannulation, which has been used historically and is currently being used in centers internationally and in the United Kingdom.

Race-Conscious Research Using Extracorporeal Life Support Organization Registry Data: A Narrative Review.

Race-conscious research identifies health disparities with 1) rigorous and responsible data collection, 2) intentionality and considered analyses, and 3) interpretation of results that advance health equity. Individual registries must overcome specific challenges to promote race-conscious research, and this paper describes ways to achieve this with a focus on the international Extracorporeal Life Support Organization (ELSO) registry. This article reviews ELSO registry publications that studied race with outcomes to consider whether research outputs align with race-conscious concepts and describe the direction of associations reported. Studies were identified via secondary analysis of a comprehensive scoping review on ECMO disparities. Of 32 multicenter publications, two (6%) studied race as the primary objective. Statistical analyses, confounder adjustment, and inclusive, antibiased language were inconsistently used. Only two (6%) papers explicitly discussed mechanistic drivers of inequity such as structural racism, and five (16%) discussed race variable limitations or acknowledged unmeasured confounders. Extracorporeal Life Support Organization registry publications demonstrated more adverse ECMO outcomes for underrepresented/minoritized populations than non-ELSO studies. With the objective to promote race-conscious ELSO registry research outputs, we provide a comprehensive understanding of race variable limitations, suggest reasoned retrospective analytic approaches, offer ways to interpret results that advance health equity, and recommend practice modifications for data collection.

Spontaneous Massive Pneumomediastinum in a Previously Well Infant With COVID-19.

A 3-month-old boy presented with a 3-hour history of a neck lump and difficulty breathing after 5 days of fever and reduced feeding. Pneumomediastinum with subcutaneous emphysema were identified, and the child was intubated because of severe work of breathing, requiring significant levels of oxygen and ventilatory pressure. Computed tomography chest scan revealed massive pneumomediastinum and significant bilateral parenchymal disease. The child deteriorated cardiovascularly, so the mediastinum was dissected by cardiothoracic surgeons and 2 drains were placed. The patient clinically improved with resolution of air leak over 2 days. A diagnosis of coronavirus disease 2019 pneumonia was confirmed.

Thrombophilia in Pediatric Patients with Multisystem Inflammatory Syndrome in Children Secondary to Coronavirus Disease 2019 Supported on Extracorporeal Membrane Oxygenation.

Coronavirus disease 2019 (COVID-19) in adults has been associated with thrombosis. Multisystem inflammatory syndrome in children (MIS-C) with COVID-19 case series have reported high fibrinogen levels, but it is not known whether this causes thrombophilia. We report two patients needing extracorporeal membrane oxygenation (ECMO) who both suffered thrombotic complications. We retrospectively reviewed patients with MIS-C needing ECMO support admitted to a single Paediatric and Cardiac Intensive Care Unit within a regional center for MIS-C in South East England. Two children required ECMO for cardiovascular support. Both developed thrombotic events despite receiving heparin infusions at dosing higher than the interquartile range for our ECMO population. Case 1 developed a right anterior and middle cerebral artery infarct, which led to his death. Case 2 had a right atrial thrombus, which resolved without complication. When compared with patients undergoing ECMO in the same institution in pre-MIS-C era, fibrinogen levels were consistently higher before and during ECMO therapy. MIS-C patients presenting with hyperfibrinogenemia are likely to have a propensity toward thrombotic complications; this must be considered when optimizing the anticoagulation strategy on ECMO.

Post-COVID-19 paediatric inflammatory multisystem syndrome: association of ethnicity, key worker and socioeconomic status with risk and severity.

OBJECTIVES: Patients from ethnic minority groups and key workers are over-represented among adults hospitalised or dying from COVID-19. In this population-based retrospective cohort, we describe the association of ethnicity, socioeconomic and family key worker status with incidence and severity of Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS). SETTING: Evelina London Children's Hospital (ELCH), the tertiary paediatric hospital for the South Thames Retrieval Service (STRS) region. PARTICIPANTS: 70 children with PIMS-TS admitted 14 February 2020-2 June 2020. OUTCOME MEASURES: Incidence and crude ORs are presented, comparing ethnicity and socioeconomic status of our cohort and the catchment population, using census data and Index of Multiple Deprivation (IMD). Regression is used to estimate the association of ethnicity and IMD with admission duration and requirement for intensive care, inotropes and ventilation. RESULTS: Incidence was significantly higher in children from black (25.0 cases per 100 000 population), Asian (6.4/100 000) and other (17.8/100 000) ethnic groups, compared with 1.6/100 000 in white ethnic groups (ORs 15.7, 4.0 and 11.2, respectively). Incidence was higher in the three most deprived quintiles compared with the least deprived quintile (eg, 8.1/100 000 in quintile 1 vs 1.6/100 000 in quintile 5, OR 5.2). Proportions of families with key workers (50%) exceeded catchment proportions. Admission length of stay was 38% longer in children from black ethnic groups than white (95% CI 4% to 82%; median 8 days vs 6 days). 9/10 children requiring ventilation were from black ethnic groups. CONCLUSIONS: Children in ethnic minority groups, living in more deprived areas and in key worker families are over-represented. Children in black ethnic groups had longer admissions; ethnicity may be associated with ventilation requirement.This project was registered with the ELCH audit and service evaluation team, ref. no 11186.

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.

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.

Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study.

BACKGROUND: Paediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS. METHODS: In this international, prospective, cross-sectional, observational study, 145 paediatric intensive care units (PICUs) from 27 countries were recruited, and over a continuous 5 day period across 10 weeks all patients were screened for enrolment. Patients were included if they had a new diagnosis of PARDS that met PALICC criteria during the study week. Exclusion criteria included meeting PARDS criteria more than 24 h before screening, cyanotic heart disease, active perinatal lung disease, and preparation or recovery from a cardiac intervention. Data were collected on the PICU characteristics, patient demographics, and elements of PARDS (ie, PARDS risk factors, hypoxaemia severity metrics, type of ventilation), comorbidities, chest imaging, arterial blood gas measurements, and pulse oximetry. The primary outcome was PICU mortality. Secondary outcomes included 90 day mortality, duration of invasive mechanical and non-invasive ventilation, and cause of death. FINDINGS: Between May 9, 2016, and June 16, 2017, during the 10 study weeks, 23 280 patients were admitted to participating PICUs, of whom 744 (3·2%) were identified as having PARDS. 95% (708 of 744) of patients had complete data for analysis, with 17% (121 of 708; 95% CI 14-20) mortality, whereas only 32% (230 of 708) of patients met Berlin criteria with 27% (61 of 230) mortality. Based on hypoxaemia severity at PARDS diagnosis, mortality was similar among those who were non-invasively ventilated and with mild or moderate PARDS (10-15%), but higher for those with severe PARDS (33% [54 of 165; 95% CI 26-41]). 50% (80 of 160) of non-invasively ventilated patients with PARDS were subsequently intubated, with 25% (20 of 80; 95% CI 16-36) mortality. By use of PALICC PARDS definition, severity of PARDS at 6 h after initial diagnosis (area under the curve [AUC] 0·69, 95% CI 0·62-0·76) discriminates PICU mortality better than severity at PARDS diagnosis (AUC 0·64, 0·58-0·71), and outperforms Berlin severity groups at 6 h (0·64, 0·58-0·70; p=0·01). INTERPRETATION: The PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS. FUNDING: University of Southern California Clinical Translational Science Institute, Sainte Justine Children's Hospital, University of Montreal, Canada, Réseau en Santé Respiratoire du Fonds de Recherche Quebec-Santé, and Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care Medicine.