Parent and staff experiences of a feasibility trial evaluating neurally adjusted ventilatory assist in infants with acute viral bronchiolitis: A qualitative study.

BACKGROUND: There is limited literature regarding family and staff experiences of participating in clinical trials. A qualitative study was embedded in the NAVABronch feasibility trial evaluating the effectiveness of a novel mode of ventilation, neurally adjusted ventilatory assist (NAVA), in infants with acute viral bronchiolitis. AIMS AND OBJECTIVES: The aim of this qualitative study was to explore the experiences of parents and health care practitioners (HCPs) involved in the NAVABronch Trial. STUDY DESIGN: Semi-structured interviews were conducted with two parents and two focus groups were held with six HCPs. FINDINGS: Four themes were identified from the focus groups: (1) Creating staff engagement, (2) Education to deliver NAVA, (3) Normalizing NAVA in clinical practice (4) Creating meaningful study outcomes and (5) support of parents during the trial, this theme was generated from the parent interviews. The findings indicated the need for education regarding NAVA for HCPs which would lead to increased confidence, better guidance around the use of NAVA and the need for NAVA to be normalized and embedded into the unit culture. Parents identified the need for further support around preparation for what may happen as a result of the interventions, particularly the weaning of sedation. CONCLUSION: Our study indicates that staff and parents had no concerns regarding the trial methods and procedures. RELEVANCE TO CLINICAL PRACTICE: Conducting clinical trials in Paediatric Intensive Care Units (PICUs) is challenging and complex. There is limited literature regarding family and staff experiences of participating in clinical trials. Understanding their experiences is crucial in ensuring trial success.

Factor XIII levels, clot strength, and impact of fibrinogen concentrate in infants undergoing cardiopulmonary bypass: a mechanistic sub-study of the FIBCON trial.

BACKGROUND: Acquired factor XIII (FXIII) deficiency after major surgery can increase postoperative bleeding. We evaluated FXIII contribution to clot strength and the effect of fibrinogen concentrate administration on FXIII activity in infants undergoing cardiac surgery using cardiopulmonary bypass. METHODS: We conducted a prospectively planned, mechanistic sub-study, nested within the Fibrinogen Concentrate Supplementation in the Management of Bleeding During Paediatric Cardiopulmonary Bypass: A Phase 1B/2A, Open-Label Dose Escalation Study (FIBCON) trial, which investigated fibrinogen concentrate supplementation during cardiopulmonary bypass (ISRCTN: 50553029) in 111 infants (median age 6.4 months). The relationships between platelet number, fibrinogen concentration, and FXIII activity with rotational thromboelastometry clot strength (EXTEM-MCF) in blood taken immediately before cardiopulmonary bypass and after separation from bypass were estimated using multivariable linear regression. Changes in coagulation variables over time were quantified using a generalised linear model comparing three groups: fibrinogen concentrate-supplemented infants, placebo, and a third cohort with lower bleeding risk. RESULTS: Overall, 48% of the variability (multivariable R2) in EXTEM-MCF clot strength was explained by three factors: the largest contribution was from FXIII activity (partial R2=0.21), followed by platelet number (partial R2=0.14), and fibrinogen concentration (partial R2=0.095). During cardiopulmonary bypass, mean platelet count fell by a similar amount in the three groups (-36% to -41%; interaction P=0.98). Conversely, fibrinogen concentration increased in all three groups: 132% in the fibrinogen concentrate-supplemented group, 26% in the placebo group, and 51% in the low-risk group. A similar increase was observed for FXIII activity (61%, 23%, and 25%, respectively; interaction P<0.0001). CONCLUSIONS: FXIII contribution to clot strength is considerable in infants undergoing cardiac surgery. Fibrinogen concentrate supplementation also increased FXIII activity, and hence clot strength. CLINICAL TRIAL REGISTRATION: ISRCTN: 50553029.

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.

Antifibrinolytic Drugs for the Prevention of Bleeding in Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Systematic Review and Meta-analysis.

BACKGROUND: Bleeding is one of the commonest complications affecting children undergoing cardiac surgery on cardiopulmonary bypass. Antifibrinolytic drugs are part of a multifaceted approach aimed at reducing bleeding, though sufficiently sized pediatric studies are sparse, and dosing algorithms are heterogeneous. Our objective was to evaluate the efficacy and safety of antifibrinolytic agents as well as the effectiveness of different dosing regimens in pediatric cardiac surgery using cardiopulmonary bypass. METHODS: We performed a systematic review and meta-analysis evaluating randomized controlled trials published between 1980 and 2019, identified by searching the databases MEDLINE, EMBASE, PubMed, and CENTRAL. All studies investigating patients <18 years of age without underlying hematological disorders were included. The primary outcome was postoperative bleeding; secondary end points included blood product transfusion, mortality, and safety (thromboses, anaphylaxis, renal or neurological dysfunction, and seizures). Different dosing regimens were compared. Studies were dual appraised, outcomes were reported descriptively and, if appropriate, quantitatively using the Review Manager 5 (REVMAN 5) software (The Cochrane Collaboration). RESULTS: Thirty of 209 articles were included, evaluating the following drugs versus control: aprotinin n = 14, tranexamic acid (TXA) n = 12, and epsilon-aminocaproic acid (EACA) n = 4. The number of participants per intervention group ranged from 11 to 100 (median, 25; interquartile range [IQR], 20.5) with a wide age span (mean, 13 days to 5.8 years) and weight range (mean, 3.1-26.3 kg). Methodological quality was low to moderate.All agents reduced mean 24-hour blood loss compared to control: aprotinin by 6.0 mL/kg (95% confidence interval [CI], -9.1 to -3.0; P = .0001), TXA by 9.0 mL/kg (95% CI, -11.3 to -6.8; P < .00001), and EACA by 10.5 mL/kg (95% CI, -21.1 to 0.0; P = .05). Heterogeneity was low for TXA (I2 = 29%; P = .19), moderate for aprotinin (I2 = 41%; P = .11), and high for EACA (I2 = 95%; P < .00001). All agents also reduced 24-hour blood product transfusion. There was no clear dose-response effect for TXA nor aprotinin. Studies were underpowered to detect significant differences in mortality, thromboses, anaphylaxis, and renal or neurological dysfunction. CONCLUSIONS: The available data demonstrate efficacy for all 3 antifibrinolytic drugs. Therefore, the agent with the most favorable safety profile should be used. As sufficient data are lacking, large comparative trials are warranted to assess the relative safety and appropriate dosing regimens in pediatrics.

Neurally Adjusted Ventilator Assist in Infants With Acute Respiratory Failure: A Literature Scoping Review.

OBJECTIVES: To map the evidence for neurally adjusted ventilatory assist strategies, outcome measures, and sedation practices in infants less than 12 months with acute respiratory failure using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidance. DATA SOURCES: CINAHL, MEDLINE, COCHRANE, JBI, EMBASE, PsycINFO, Google scholar, BNI, AMED. Trial registers included the following: ClinicalTrials.gov, European Union clinical trials register, International Standardized Randomized Controlled Trial Number register. Also included were Ethos, Grey literature, Google, dissertation abstracts, EMBASE conference proceedings. STUDY SELECTION: Abstracts were screened followed by review of full text. Articles incorporating a heterogeneous population of both infants and older children were assessed, and where possible, data for infants were extracted. Fifteen articles were included. Ten articles were primary research: randomized controlled trial (n = 3), cohort studies (n = 4), retrospective data analysis (n = 2), case series (n = 1). Other articles are expert opinion (n = 2), neurally adjusted ventilatory assist updates (n = 1), and a literature review (n = 2). Three studies included exclusively infants. We also included 12 studies reporting jointly on infants and children. DATA EXTRACTION: A standardized data extraction tool was used. DATA SYNTHESIS: Key findings were that evidence related to neurally adjusted ventilatory assist ventilation strategies in infants and related to specific primary conditions is limited. The setting of neurally adjusted ventilatory assist level is not consistent, and how to optimize this mode of ventilation was not documented. Outcome measures varied considerably, most studies focused on improvements in respiratory and physiological variables. Sedation use is variable with regard to medication type and dose. There is an indication that less sedation is required in patients receiving neurally adjusted ventilatory assist, but no conclusive evidence to support this. CONCLUSIONS: This review highlights a lack of standardized strategies for neurally adjusted ventilatory assist ventilation and sedation practices among infants with acute respiratory failure. Studies were limited by small sample sizes and a lack of focus on specific patient groups. Robust studies are needed to provide evidence-based clinical recommendations for the use of neurally adjusted ventilatory assist in infants with acute respiratory failure.

Degradation of the Endothelial Glycocalyx Contributes to Metabolic Acidosis in Children Following Cardiopulmonary Bypass Surgery.

OBJECTIVES: Cardiopulmonary bypass surgery is complicated by metabolic acidosis, microvascular dysfunction, and capillary leak. The glycocalyx-a layer of proteins and sugars lining the vascular endothelium-is degraded during cardiopulmonary bypass. We aimed to describe the kinetics of glycocalyx degradation during and following cardiopulmonary bypass. We hypothesized that cleavage of negatively charged fragments of the glycocalyx would directly induce metabolic acidosis through changes in the strong ion gap (defined using Stewart's physicochemical approach to acid-base chemistry). We also investigated whether glycocalyx degradation was associated with failure of endothelial function and cardiovascular dysfunction. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed surgical/medical PICU. PATIENTS: Twenty-seven term infants and children requiring cardiopulmonary bypass surgery for the correction/palliation of congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recruited 27 patients, 5 days to 57 months old. We prospectively sampled plasma prior to, during, and following cardiopulmonary bypass at predefined time points. We measured plasma concentrations of interleukin-6 (inflammatory marker), heparan sulfate (negatively charged glycocalyx glycosaminoglycan), and syndecan-1 (neutrally charged glycocalyx protein). We defined the following outcome measures: metabolic acidosis (strong ion gap), renal dysfunction (fold change in creatinine), capillary leak (fluid bolus volume), cardiovascular dysfunction (Vasoactive Inotropic Score), and length of ventilation. In linear regression models, maximum measured heparan sulfate concentration (negatively charged) was associated with metabolic acidosis (p = 0.016), renal dysfunction (p = 0.009), and length of ventilation (p = 0.047). In contrast, maximum measured syndecan-1 concentration (neutrally charged) was not associated with these clinical endpoints (p > 0.30 for all). CONCLUSIONS: Our data show that metabolic acidosis (increased strong ion gap) is associated with plasma concentration of heparan sulfate, a negatively charged glycosaminoglycan cleaved from the endothelial glycocalyx during cardiopulmonary bypass. In addition, cleavage of heparan sulfate was associated with renal dysfunction, capillary leak, and global markers of cardiovascular dysfunction. These data highlight the importance of designing translational therapies to protect the glycocalyx in cardiopulmonary bypass.

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."

Recommendations for hemodynamic monitoring for critically ill children-expert consensus statement issued by the cardiovascular dynamics section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).

BACKGROUND: Cardiovascular instability is common in critically ill children. There is a scarcity of published high-quality studies to develop meaningful evidence-based hemodynamic monitoring guidelines and hence, with the exception of management of shock, currently there are no published guidelines for hemodynamic monitoring in children. The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Cardiovascular Dynamics section aimed to provide expert consensus recommendations on hemodynamic monitoring in critically ill children. METHODS: Creation of a panel of experts in cardiovascular hemodynamic assessment and hemodynamic monitoring and review of relevant literature-a literature search was performed, and recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. The AGREE statement was followed to prepare this document. RESULTS: Of 100 suggested recommendations across 12 subgroups concerning hemodynamic monitoring in critically ill children, 72 reached "strong agreement," 20 "weak agreement," and 2 had "no agreement." Six statements were considered as redundant after rephrasing of statements following the first round of voting. The agreed 72 recommendations were then coalesced into 36 detailing four key areas of hemodynamic monitoring in the main manuscript. Due to a lack of published evidence to develop evidence-based guidelines, most of the recommendations are based upon expert consensus. CONCLUSIONS: These expert consensus-based recommendations may be used to guide clinical practice for hemodynamic monitoring in critically ill children, and they may serve as a basis for highlighting gaps in the knowledge base to guide further research in hemodynamic monitoring.

A tool for routine monitoring and feedback of morbidities following paediatric cardiac surgery.

Short-term survival after paediatric cardiac surgery has improved significantly over the past 20 years and increasing attention is being given to measuring and reducing incidence of morbidities following surgery. How to best use routinely collected data to share morbidity information constitutes a challenge for clinical teams interested in analysing their outcomes for quality improvement. We aimed to develop a tool facilitating this process in the context of monitoring morbidities following paediatric cardiac surgery, as part of a prospective multi-centre research study in the United Kingdom.We developed a prototype software tool to analyse and present data about morbidities associated with cardiac surgery in children. We used an iterative process, involving engagement with potential users, tool design and implementation, and feedback collection. Graphical data displays were based on the use of icons and graphs designed in collaboration with clinicians.Our tool enables automatic creation of graphical summaries, displayed as a Microsoft PowerPoint presentation, from a spreadsheet containing patient-level data about specified cardiac surgery morbidities. Data summaries include numbers/percentages of cases with morbidities reported, co-occurrences of different morbidities, and time series of each complication over a time window.Our work was characterised by a very high level of interaction with potential users of the tool, enabling us to promptly account for feedback and suggestions from clinicians and data managers. The United Kingdom centres involved in the project received the tool positively, and several expressed their interest in using it as part of their routine practice.

Permissive versus restrictive temperature thresholds in critically ill children with fever and infection: a multicentre randomized clinical pilot trial.

BACKGROUND: Fever improves pathogen control at a significant metabolic cost. No randomized clinical trials (RCT) have compared fever treatment thresholds in critically ill children. We performed a pilot RCT to determine whether a definitive trial of a permissive approach to fever in comparison to current restrictive practice is feasible in critically ill children with suspected infection. METHODS: An open, parallel-group pilot RCT with embedded mixed methods perspectives study in four UK paediatric intensive care units (PICUs) and associated retrieval services. Participants were emergency PICU admissions aged > 28 days to < 16 years receiving respiratory support and supplemental oxygen. Subjects were randomly assigned to permissive (antipyretic interventions only at ≥ 39.5 °C) or restrictive groups (antipyretic interventions at ≥ 37.5 °C) whilst on respiratory support. Parents were invited to complete a questionnaire or take part in an interview. Focus groups were conducted with staff at each unit. Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between group separation of temperature and safety. RESULTS: One hundred thirty-eight children met eligibility criteria of whom 100 (72%) were randomized (11.1 patients per month per site) without prior consent (RWPC). Consent to continue in the trial was obtained in 87 cases (87%). The mean maximum temperature (95% confidence interval) over the first 48 h was 38.4 °C (38.2-38.6) in the restrictive group and 38.8 °C (38.6-39.1) in the permissive group, a mean difference of 0.5 °C (0.2-0.8). Protocol deviations were observed in 6.8% (99/1438) of 6-h time periods and largely related to patient comfort in the recovery phase. Length of stay, duration of organ support and mortality were similar between groups. No pre-specified serious adverse events occurred. Staff (n = 48) and parents (n = 60) were supportive of the trial, including RWPC. Suggestions were made to only include invasively ventilated children for the duration of intubation. CONCLUSION: Uncertainty around the optimal fever threshold for antipyretic intervention is relevant to many emergency PICU admissions. A more permissive approach was associated with a modest increase in mean maximum temperature. A definitive trial should focus on the most seriously ill cases in whom antipyretics are rarely used for their analgesic effects alone. TRIAL REGISTRATION: ISRCTN16022198 . Registered on 14 August 2017.

Strategies for Prevention and Management of Bleeding Following Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Scoping Review.

OBJECTIVE: We aimed to systematically describe, via a scoping review, the literature reporting strategies for prevention and management of mediastinal bleeding post pediatric cardiopulmonary bypass surgery. DATA SOURCES: MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL Register. STUDY SELECTION: Two authors independently screened publications from 1980 to 2016 reporting the effect of therapeutic interventions on bleeding-related postoperative outcomes, including mediastinal drain loss, transfusion, chest re-exploration rate, and coagulation variables. Inclusions: less than 18 years, cardiac surgery on cardiopulmonary bypass. DATA EXTRACTION: Data from eligible studies were extracted using a standard data collection sheet. DATA SYNTHESIS: Overall, 299 of 7,434 screened articles were included, with observational studies being almost twice as common (n = 187, 63%) than controlled trials (n = 112, 38%). The most frequently evaluated interventions were antifibrinolytic drugs (75 studies, 25%), blood products (59 studies, 20%), point-of-care testing (47 studies, 16%), and cardiopulmonary bypass circuit modifications (46 studies, 15%). The publication rate for controlled trials remained constant over time (4-6/yr); however, trials were small (median participants, 51; interquartile range, 57) and overwhelmingly single center (98%). Controlled trials originated from 22 countries, with the United States, India, and Germany accounting for 50%. The commonest outcomes were mediastinal blood loss and transfusion requirements; however, these were defined inconsistently (blood loss being reported over nine different time periods). The majority of trials were aimed at bleeding prevention (98%) rather than treatment (10%), nine studies assessed both. CONCLUSIONS: Overall, this review demonstrates small trial sizes, low level of evidence, and marked heterogeneity of reported endpoints in the included studies. The need for more, higher quality studies reporting clinically relevant, comparable outcomes is highlighted. Emerging fields such as the use of coagulation factor concentrates, goal-directed guidelines, and anti-inflammatory therapies appear to be of particular interest. This scoping review can potentially guide future trial design and form the basis for therapy-specific systematic reviews.

Results of balloon pulmonary valvoplasty in children with Noonan's syndrome.

Pulmonary valve stenosis is common in patients with Noonan's syndrome. The response to balloon valvoplasty varies.We assessed the correlation between re-intervention rate, immediate response, and the progress of the valve gradient over time after intervention. METHODS: This is a retrospective study conducted from 1995 to 2014. RESULTS: Of 14 patients identified, seven had re-intervention 28±54 months (range 3-149, median 3.3) after valvoplasty. These patients did not have a significant decrease in gradient after intervention. Their gradient subsequently decreased during follow-up and then became static before increasing years after intervention. In contrast, the gradient of patients not requiring further intervention continually reduced over time. Demographics did not differ between these groups. CONCLUSION: We could not identify predisposing factors for long-term success of pulmonary valvoplasty in Noonan's patients, but the trajectory of gradients differs significantly between patients needing re-intervention from those who remain free from re-intervention.

Validation of the Brief Developmental Assessment in pre-school children with heart disease.

Introduction The objective of this study was to prospectively validate the "Brief Developmental Assessment", which is a new early recognition tool for neurodevelopmental abnormalities in children with heart disease that was developed for use by cardiac teams. METHODS: This was a prospective validation study among a representative sample of 960 pre-school children with heart disease from three United Kingdom tertiary cardiac centres who were analysed grouped into five separate age bands. RESULTS: The "Brief Developmental Assessment" was successfully validated in the older four age bands, but not in the youngest representing infants under the age of 4 months, as pre-set validation thresholds were met - lower 95% confidence limit for the correlation coefficient above 0.75 - in terms of agreement of scores between two raters and with an external measure the "Mullen Scales of Early Learning". On the basis of American Association of Pediatrics Guidelines, which state that the sensitivity and specificity of a developmental screening tool should fall between 70 and 80%, "Brief Developmental Assessment" outcome of Red meets this threshold for detection of Mullen scores >2 standard deviations below the mean. CONCLUSION: The "Brief Developmental Assessment" may be used to improve the quality of assessment of children with heart disease. This will require a training package for users and a guide to action for abnormal results. Further research is needed to determine how best to deploy the "Brief Developmental Assessment" at different time points in children with heart disease and to determine the management strategy in infants younger than 4 months old.

Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.

BACKGROUND: Impregnated central venous catheters are recommended for adults to reduce bloodstream infections but not for children because there is not enough evidence to prove they are effective. We aimed to assess the effectiveness of any type of impregnation (antibiotic or heparin) compared with standard central venous catheters to prevent bloodstream infections in children needing intensive care. METHODS: We did a randomised controlled trial of children admitted to 14 English paediatric intensive care units. Children younger than 16 years were eligible if they were admitted or being prepared for admission to a participating paediatric intensive care unit and were expected to need a central venous catheter for 3 or more days. Children were randomly assigned (1:1:1) to receive a central venous catheter impregnated with antibiotics, a central venous catheter impregnated with heparin, or a standard central venous catheter with computer generated randomisation in blocks of three and six, stratified by method of consent, site, and envelope storage location within the site. The clinician responsible for inserting the central venous catheter was not masked to allocation, but allocation was concealed from patients, their parents, and the paediatric intensive care unit personnel responsible for their care. The primary outcome was time to first bloodstream infection between 48 h after randomisation and 48 h after central venous catheter removal with impregnated (antibiotic or heparin) versus standard central venous catheters, assessed in the intention-to-treat population. Safety analyses compared central venous catheter-related adverse events in the subset of children for whom central venous catheter insertion was attempted (per-protocol population). This trial is registered with ISRCTN number, ISRCTN34884569. FINDINGS: Between Nov 25, 2010, and Nov 30, 2012, 1485 children were recruited to this study. We randomly assigned 502 children to receive standard central venous catheters, 486 to receive antibiotic-impregnated catheters, and 497 to receive heparin-impregnated catheters. Bloodstream infection occurred in 18 (4%) of those in the standard catheters group, 7 (1%) in the antibiotic-impregnated group, and 17 (3%) assigned to heparin-impregnated catheters. Primary analyses showed no effect of impregnated (antibiotic or heparin) catheters compared with standard central venous catheters (hazard ratio [HR] for time to first bloodstream infection 0.71, 95% CI 0.37-1.34). Secondary analyses showed that antibiotic central venous catheters were better than standard central venous catheters (HR 0.43, 0.20-0.96) and heparin central venous catheters (HR 0.42, 0.19-0.93), but heparin did not differ from standard central venous catheters (HR 1.04, 0.53-2.03). Clinically important and statistically significant absolute risk differences were identified only for antibiotic-impregnated catheters versus standard catheters (-2.15%, 95% CI -4.09 to -0.20; number needed to treat [NNT] 47, 95% CI 25-500) and antibiotic-impregnated catheters versus heparin-impregnated catheters (-1.98%, -3.90 to -0.06, NNT 51, 26-1667). Nine children (2%) in the standard central venous catheter group, 14 (3%) in the antibiotic-impregnated group, and 8 (2%) in the heparin-impregnated group had catheter-related adverse events. 45 (8%) in the standard group, 35 (8%) antibiotic-impregnated group, and 29 (6%) in the heparin-impregnated group died during the study. INTERPRETATION: Antibiotic-impregnated central venous catheters significantly reduced the risk of bloodstream infections compared with standard and heparin central venous catheters. Widespread use of antibiotic-impregnated central venous catheters could help prevent bloodstream infections in paediatric intensive care units. FUNDING: National Institute for Health Research, UK.

Attitudes towards fever amongst UK paediatric intensive care staff.

The role played by fever in the outcome of critical illness in children is unclear. This survey of medical and nursing staff in 35 paediatric intensive care units and transport teams in the United Kingdom and Ireland established attitudes towards the management of children with fever. Four hundred sixty-two medical and nursing staff responded to a web-based survey request. Respondents answered eight questions regarding thresholds for temperature control in usual clinical practice, indications for paracetamol use, and readiness to participate in a clinical trial of permissive temperature control. The median reported threshold for treating fever in clinical practice was 38 °C (IQR 38-38.5 °C). Paracetamol was reported to be used as an analgesic and antipyretic but also for non-specific comfort indications. There was a widespread support for a clinical trial of a permissive versus a conservative approach to fever in paediatric intensive care units. Within a trial, 58% of the respondents considered a temperature of 39 °C acceptable without treatment. CONCLUSIONS: Staff on paediatric intensive care units in the United Kingdom and Ireland tends to treat temperatures within the febrile range. There was a willingness to conduct a randomized controlled trial of treatment of fever. What is known: • The effect of fever on the outcome in paediatric critical illness is unknown. • Paediatricians have traditionally been reluctant to allow fever in sick children. What is new: • Paediatric intensive care staff report a tendency towards treating fever, with a median reported treatment threshold of 38 °C. • There is widespread support amongst PICU staff in the UK for a randomized controlled trial of temperature in critically ill children. • Within a trial setting, PICU staff attitudes to fever are more permissive than in clinical practice.

Is the medical treatment for arterial hypertension after primary aortic coarctation repair related to age at surgery? A retrospective cohort study.

BACKGROUND: Hypertension following primary coarctation repair affects up to a third of subjects. A number of studies suggest that future hypertension risk is reduced if primary repair is performed at a younger age. OBJECTIVES: The objective of this study was to evaluate the risk of future medical treatment for hypertension depending on age of primary coarctation repair. METHODS: This study was carried out at a tertiary paediatric cardiology referral centre. Retrospective database evaluation of children aged 28 days and ⩽12 months), and children (>12 months). Main outcome measure is the need for long-term anti-hypertensive medication. The risk for re-coarctation was also evaluated. RESULTS: A total of 87 patients were analysed: 60 neonates, 17 infants, 10 children. Among them, 6.7% neonates, 29.4% infants, and 40% children required long-term anti-hypertensive medications. Group differences were statistically significant (p=0.004). After adjustment for type of repair, the risk of long-term anti-hypertensive therapy was 4.5 (95% confidence interval 1.2-16.9, p=0.025) and 10.5 times (95% confidence interval 2.6-42.3, p=0.001) higher if primary repair was carried out in infancy and childhood, respectively, compared with neonates. Among all, 13 patients developed re-coarctation: 21.7% in the neonatal group, 5.9% in the infant group, and 20% in the child group. We could not demonstrate a significant difference between these proportions or calculate a reliable risk for developing re-coarctation. CONCLUSIONS: Risk of medical treatment for hypertension was lowest when primary repair was carried out during the neonatal period, rising 10-fold if first operated on as a child. Knowing the likelihood of hypertension development depending on age of primary repair is useful for long-term surveillance and counselling.

Monitoring quality of care through linkage of administrative data: national trends in bloodstream infection in U.K. PICUs 2003-2012.

OBJECTIVES: Interventions to reduce hospital-acquired bloodstream infection have succeeded in reducing rates in U.S. PICUs, but there is a lack of evidence for the impact of similar interventions in the United Kingdom. We assessed variation in bloodstream infection rates within and between PICUs over a 10-year period, during which time infection control strategies (care bundles) were implemented. DESIGN: Observational study linking laboratory data to national audit data of pediatric intensive care admissions (Paediatric Intensive Care Audit Network). SETTING: Twenty PICUs in England and Wales, 2003-2012. PATIENTS: One hundred and two thousand nine hundred ninety-nine children less than 16 years. INTERVENTIONS: Implementation of infection control strategies in PICU captured through a survey of clinicians. MEASUREMENTS AND MAIN RESULTS: Rates of bloodstream infection per 1,000 bed-days were estimated from samples taken between 2 days after admission and up to 2 days following discharge from PICU. Two percent of children experienced at least one bloodstream infection, corresponding to 5.11 (95% CI, 4.90-5.31) per 1,000 bed-days. There was a significant difference in trends preimplementation of infection control strategies (annual decrease of 8.0%; 95% CI, 6.3-9.7%) versus postimplementation (annual decrease of 13.4%; 95% CI, 10.3-16.4%). By 24 months postimplementation, the rate of bloodstream infection had fallen 25.5% and was 15.1% lower than would have been expected if preimplementation trends had continued. CONCLUSIONS: Our population-based study of PICUs in England and Wales demonstrates a steady decline in bloodstream infection rates over time. In addition, there was a significant and incremental further decrease in rates associated with timing of implementation of infection control strategies. Assessment of bloodstream infection trends before as well as after implementation of infection control strategies can be facilitated using data linkage and is important to avoid overestimating the impact of unit-level interventions to improve infection control. Advances in collection and linkage of real-time data could further support quality improvement efforts.

Relationship between arterial partial oxygen pressure after resuscitation from cardiac arrest and mortality in children.

BACKGROUND: Observational studies in adults have shown a worse outcome associated with hyperoxia after resuscitation from cardiac arrest. Extrapolating from adult data, current pediatric resuscitation guidelines recommend avoiding hyperoxia. We investigated the relationship between arterial partial oxygen pressure and survival in patients admitted to the pediatric intensive care unit (PICU) after cardiac arrest. METHODS AND RESULTS: We conducted a retrospective cohort study using the Pediatric Intensive Care Audit Network (PICANet) database between 2003 and 2010 (n=122,521). Patients aged <16 years with documented cardiac arrest preceding PICU admission and arterial blood gas analysis taken within 1 hour of PICU admission were included. The primary outcome measure was death within the PICU. The relationship between postarrest oxygen status and outcome was modeled with logistic regression, with nonlinearities explored via multivariable fractional polynomials. Covariates included age, sex, ethnicity, congenital heart disease, out-of-hospital arrest, year, Pediatric Index of Mortality-2 (PIM2) mortality risk, and organ supportive therapies. Of 1875 patients, 735 (39%) died in PICU. Based on the first arterial gas, 207 patients (11%) had hyperoxia (Pa(O)(2) ≥300 mm Hg) and 448 (24%) had hypoxia (Pa(O)(2) <60 mm Hg). We found a significant nonlinear relationship between Pa(O)(2) and PICU mortality. After covariate adjustment, risk of death increased sharply with increasing hypoxia (odds ratio, 1.92; 95% confidence interval, 1.80-2.21 at Pa(O)(2) of 23 mm Hg). There was also an association with increasing hyperoxia, although not as dramatic as that for hypoxia (odds ratio, 1.25; 95% confidence interval, 1.17-1.37 at 600 mm Hg). We observed an increasing mortality risk with advancing age, which was more pronounced in the presence of congenital heart disease. CONCLUSIONS: Both severe hypoxia and, to a lesser extent, hyperoxia are associated with an increased risk of death after PICU admission after cardiac arrest.