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.

Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions.

BACKGROUND: Renovascular hypertension (RenoVH) is a cause of hypertension in children. A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling. This longitudinal observational study aims to describe occurrence of cardiovascular changes secondary to RenoVH and also any improvement in cardiac remodelling after successful endovascular and/or surgical intervention. METHODS: All patients with RenoVH referred to our centre, who received ≥ 1 endovascular intervention (some had also undergone surgical interventions) were included. Data were collected by retrospective database review over a 22-year period. We assessed oscillometric blood pressure and eight echocardiographic parameters pre- and post-intervention. RESULTS: One hundred fifty-two patients met inclusion criteria and had on average two endovascular interventions; of these children, six presented in heart failure. Blood pressure (BP) control was achieved by 54.4% of patients post-intervention. Average z-scores improved in interventricular septal thickness in diastole (IVSD), posterior Wall thickness in diastole (PWD) and fractional shortening (FS); left ventricular mass index (LVMI) and relative wall thickness (RWT) also improved. PWD saw the greatest reduction in mean difference in children with abnormal (z-score reduction 0.25, p < 0.001) and severely abnormal (z-score reduction 0.23, p < 0.001) z-scores between pre- and post-intervention echocardiograms. Almost half (45.9%) had reduction in prescribed antihypertensive medications, and 21.3% could discontinue all antihypertensive therapy. CONCLUSIONS: Our study reports improvement in cardiac outcomes after endovascular + / - surgical interventions. This is evidenced by BP control, and echocardiogram changes in which almost half achieved normalisation in systolic BP readings and reduction in the number of children with abnormal echocardiographic parameters. A higher resolution version of the Graphical abstract is available as Supplementary information.

Protocol for a Randomized Controlled Trial to Evaluate a Permissive Blood Pressure Target Versus Usual Care in Critically Ill Children with Hypotension (PRESSURE).

OBJECTIVES: Management of hypotension is a fundamental part of pediatric critical care, with cardiovascular support in the form of fluids or vasoactive drugs offered to every hypotensive child. However, optimal blood pressure (BP) targets are unknown. The PRotocolised Evaluation of PermiSSive BP Targets Versus Usual CaRE (PRESSURE) trial aims to evaluate the clinical and cost-effectiveness of a permissive mean arterial pressure (MAP) target of greater than a fifth centile for age compared with usual care. DESIGN: Pragmatic, open, multicenter, parallel-group randomized control trial (RCT) with integrated economic evaluation. SETTING: Eighteen PICUs across the United Kingdom. PATIENTS: Infants and children older than 37 weeks corrected gestational age to 16 years accepted to a participating PICU, on mechanical ventilation and receiving vasoactive drugs for hypotension. INTERVENTIONS: Adjustment of hemodynamic support to achieve a permissive MAP target greater than fifth centile for age during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a permissive MAP target or usual care, stratified by site and age group. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred until after randomization. The primary clinical outcome is a composite of death and days of ventilatory support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of BP and organ support, and discharge outcomes. This RCT received Health Research Authority approval (reference 289545), and a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee on May 10, 2021 (reference number 21/EE/0084). The trial is registered and has an International Standard RCT Number (reference 20609635). CONCLUSIONS: Trial findings will be disseminated in U.K. national and international conferences and in peer-reviewed journals.

Prescription of Steroids in General Pediatric Intensive Care Patients-A Two-Center Retrospective Observational Study.

OBJECTIVES: Designing randomized trials to determine utility, dose, and timing of steroid administration in the management of critically unwell children may be difficult owing to a high proportion of patients who receive steroid as part of current care. We aimed to describe steroid use among all patients on two general PICUs. DESIGN: Retrospective observational study using a multilevel logistic regression model. SETTING: Two tertiary, general mixed medical and surgical PICUs. PATIENTS: All admissions between 2016 and 2019. All parenteral or enteral steroid prescriptions were identified, and steroid type, frequency, timing, and peak daily doses were recorded. The outcome measure was mortality prior to PICU discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 5,483 admissions during the study period, and 1,804 (33%) of these involved prescription of at least one steroid. Among patients prescribed steroids, the median peak daily dose when steroids were prescribed was 2.4 mg/kg/d prednisolone equivalent (interquartile range, 1.6-3.6), and the median time to peak steroid doses was 2 days (1-5 d). Administration of steroid was associated with increased risk-adjusted mortality odds ratio (OR) of 1.37 (95% CI, 1.04-1.79). Steroids were prescribed in 42.3% of admissions, in which the child did not survive to PICU discharge. Among children who were prescribed steroids, use of hydrocortisone (OR, 6.75; 95% CI, 3.79-12.27) and methylprednisolone (OR, 7.85; 95% CI, 4.21-14.56), or starting steroids later than 2 days after PICU admission were associated with an increased mortality (OR, 1.93; 95% CI, 1.15-3.25). CONCLUSIONS: Steroids are widely used in pediatric critical illness and nonsurvival associated with increased frequency of use. This association appears to be related to steroid class and timing of dose, both likely to reflect indication for steroid prescription. Prospective trials are required to estimate these complex risks and benefits, and study design will need to consider these patterns.

Randomization to a Liberal Versus Conservative Oxygenation Target: Redox Responses in Critically Ill Children.

RATIONALE: Optimal systemic oxygenation targets in pediatric critical illness are unknown. A U-shaped relationship exists between blood oxygen levels and PICU mortality. Redox stress or iatrogenic injury from intensive treatments are potential mechanisms of harm from hyperoxia. OBJECTIVES: To measure biomarkers of oxidative status in children admitted to PICU and randomized to conservative (oxygen-hemoglobin saturation [Sp o2 ] 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation targets. DESIGN: Mechanistic substudy nested within the Oxygen in PICU (Oxy-PICU) pilot randomized feasibility clinical trial ( ClinicalTrials.gov : NCT03040570). SETTING: Three U.K. mixed medical and surgical PICUs in university hospitals. PATIENTS: Seventy-five eligible patients randomized to the Oxy-PICU randomized feasibility clinical trial. INTERVENTIONS: Randomization to a conservative (Sp o2 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation target. MEASUREMENTS AND MAIN RESULTS: Blood and urine samples were collected at two timepoints: less than 24 hours and up to 72 hours from randomization in trial participants (March 2017 to July 2017). Plasma was analyzed for markers of ischemic/oxidative response, namely thiobarbituric acid-reactive substances (TBARS; lipid peroxidation marker) and ischemia-modified albumin (protein oxidation marker). Total urinary nitrate/nitrite was measured as a marker of reactive oxygen and nitrogen species (RONS). Blood hypoxia-inducible factor (HIF)-1a messenger RNA (mRNA) expression (hypoxia response gene) was measured by reverse transcription- polymerase chain reaction. Total urinary nitrate/nitrite levels were greater in the liberal compared with conservative oxygenation group at 72 hours (median difference 32.6 µmol/mmol of creatinine [95% CI 13.7-93.6]; p < 0.002, Mann-Whitney test). HIF-1a mRNA expression was increased in the conservative group compared with liberal in less than 24-hour samples (6.0-fold [95% CI 1.3-24.0]; p = 0.032). There were no significant differences in TBARS or ischemia-modified albumin. CONCLUSIONS: On comparing liberal with conservative oxygenation targets, we show, first, significant redox response (increase in urinary markers of RONS), but no changes in markers of lipid or protein oxidation. We also show what appears to be an early hypoxic response (increase in HIF-1a gene expression) in subjects exposed to conservative rather than liberal oxygenation targets.

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.

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Pediatric Intensive Care.

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Sp o2 ) target of 88-92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Sp o2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Sp o2 target of more than 94% or a conservative Sp o2 target of 88-92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals.

Functional outcomes at PICU discharge in hemato-oncology children at a tertiary oncology center in Hong Kong.

BACKGROUND: Advancements in cancer treatment have resulted in longer survival but often at the expense of new therapy-associated morbidities. The aim of this study is to evaluate functional outcomes of hemato-oncology patients at PICU discharge, and to identify associated risk factors. METHODS: A single-center retrospective observational study. All children (< 19 years) with a hemato-oncology diagnosis admitted to the Hong Kong Children's Hospital PICU over a 2-year period were included. Functional status upon admission and discharge were compared. Univariable and multi-variable analyses were employed to identify risk factors associated with new morbidities. RESULTS: Out of 288 PICU admissions, there were 277 live discharges (mortality 4%), of which 52 (18.8%) developed new morbidities. Emergency admission, severity of illness at admission, organ dysfunction and support were associated with new morbidities (OR 1.08-11.96; p < 0.05). Adjusting for confounding factors, higher Pediatric Logistic Organ Dysfunction 2 score at admission was significantly associated with development of new morbidities (OR 1.34; 95% CI 1.18-1.54; p < 0.001). CONCLUSION: Critically ill children with hemato-oncological diseases had a higher rate of developing new morbidities (18.8%) compared with the general PICU population (4-8%). This was associated with severity of illness at admission. Further work is warranted to understand the lasting effects of these new morbidities and mitigating interventions.

Research Priorities for U.K. Pediatric Critical Care in 2019: Healthcare Professionals' and Parents' Perspectives.

OBJECTIVES: The Paediatric Intensive Care Society Study Group conducted a research prioritization exercise with the aim to identify and agree research priorities in Pediatric Critical Care in the United Kingdom both from a healthcare professional and parent/caregiver perspective. DESIGN: A modified three-round e-Delphi survey, followed by a survey of parents of the top 20 healthcare professional priorities. SETTING: U.K. PICUs. PATIENTS: U.K. PICU healthcare professionals who are members of the professional society and parents and family members of children, with experience of a U.K. PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-nine healthcare professional submitted topics in round 1, 98 participated in round 2, and 102 in round 3. These topics were categorized into eight broad domain areas, and within these, there were 73 specific topics in round 2. At round 3, 18 topics had a mean score less than 5.5 and were removed, leaving 55 topics for ranking in round 3. Ninety-five parents and family members completed the surveys from at least 17 U.K. PICUs. Both parents and healthcare professional prioritized research topics associated with the PICU workforce. Healthcare professional research priorities reflected issues that impacted on day-to-day management and practice. Parents' prioritized research addressing acute situations such as infection identification of and sepsis management or research addressing long-term outcomes for children and parents after critical illness. Parents prioritized research into longer term outcomes more than healthcare professional. Parental responses showed clear support for the concept of research in PICU, but few novel research questions were proposed. CONCLUSIONS: This is the first research prioritization exercise within U.K. PICU setting to include parents' and families' perspectives and compare these with healthcare professional. Results will guide both funders and future researchers.

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."

How 217 Pediatric Intensivists Manage Anemia at PICU Discharge: Online Responses to an International Survey.

OBJECTIVE: To describe the management of anemia at PICU discharge by pediatric intensivists. DESIGN: Self-administered, online, scenario-based survey. SETTING: PICUs in Australia/New Zealand, Europe, and North America. SUBJECTS: Pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respondents were asked to report their decisions regarding RBC transfusions, iron, and erythropoietin prescription to children ready to be discharged from PICU, who had been admitted for hemorrhagic shock, cardiac surgery, craniofacial surgery, and polytrauma. Clinical and biological variables were altered separately in order to assess their effect on the management of anemia. Two-hundred seventeen responses were analyzed. They reported that the mean (± SEM) transfusion threshold was a hemoglobin level of 6.9 ± 0.09 g/dL after hemorrhagic shock, 7.6 ± 0.10 g/dL after cardiac surgery, 7.0 ± 0.10 g/dL after craniofacial surgery, and 7.0 ± 0.10 g/dL after polytrauma (p < 0.001). The most important increase in transfusion threshold was observed in the presence of a cyanotic heart disease (mean increase ranging from 1.80 to 2.30 g/dL when compared with baseline scenario) or left ventricular dysfunction (mean increase, 1.41-2.15 g/dL). One third of respondents stated that they would not prescribe iron at PICU discharge, regardless of the hemoglobin level or the baseline scenario. Most respondents (69.4-75.0%, depending on the scenario) did not prescribe erythropoietin. CONCLUSIONS: Pediatric intensivists state that they use restrictive transfusion strategies at PICU discharge similar to those they use during the acute phase of critical illness. Supplemental iron is less frequently prescribed than RBCs, and prescription of erythropoietin is uncommon. Optimal management of post-PICU anemia is currently unknown. Further studies are required to highlight the consequences of this anemia and to determine appropriate management.

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.

Comparative evaluation of Airtraq™ and GlideScope® videolaryngoscopes for difficult pediatric intubation in a Pierre Robin manikin.

Airway management in children is associated with anatomical and physiological challenges compared with adults. Pierre Robin sequence (PRS) is a condition characterized by micrognathia, glossoptosis, and cleft palate and related to a difficult airway. Both the Airtraq™ and GlideScope® have never been previously directly compared in PRS. Our aim was to evaluate the performance of these two airway devices in a PRS manikin for ethical and practical reasons. Between April and July 2017, 26, pediatric intensive care clinical fellows or trainees from a tertiary pediatric center were recruited to participate. In this prospective and randomized crossover trial, all participants first set up the Airtraq™ and the GlideScope® and then used these videolaryngoscopes to intubate an AirSim® PRS manikin. Our primary outcome measure was the duration of the successful intubation attempt. Duration of the successful intubation attempt was 18.1 (14.2-34.9 [10.2-51.3]) s for the Airtraq™ compared to 31.1 (18.7-55.6 [6.2-119]) s for the GlideScope® (p = 0.045). Setup time was 50.0 ± 6.9 s for the Airtraq™ and 27.8 ± 8.6 s for the GlideScope® (p < 0.001).Conclusion: Even though setup time was longer, the characteristics of intubation performance were superior with the Airtraq™ relative to the GlideScope® in an AirSim® PRS manikin. What is Known: • Several case reports have described the successful use of Airtraq™ to intubate children with Pierre Robin sequence. • The GlideScope® has demonstrated similar rates of first-attempt successful intubation to flexible fiberoptic bronchoscopy in a Pierre Robin sequence manikin. What is New: • In the hands of pediatric non-airway specialists, the characteristics of intubation performance, including the duration of the successful intubation attempt, are superior with the Airtraq™ compared with the GlideScope® in a Pierre Robin sequence manikin. • Setup time for the Airtraq™ is, however, longer relative to that for the GlideScope®.

The Inadequate Oxygen Delivery Index and Low Cardiac Output Syndrome Score As Predictors of Adverse Events Associated With Low Cardiac Output Syndrome Early After Cardiac Bypass.

OBJECTIVES: To evaluate the effectiveness of two scoring systems, the inadequate oxygen delivery index, a risk analytics algorithm (Etiometry, Boston, MA) and the Low Cardiac Output Syndrome Score, in predicting adverse events recognized as indicative of low cardiac output syndrome within 72 hours of surgery. DESIGN: A retrospective observational pair-matched study. SETTING: Tertiary pediatric cardiac ICU. PATIENTS: Children undergoing cardiac bypass for congenital heart defects. Cases experienced an adverse event linked to low cardiac output syndrome in the 72 hours following surgery (extracorporeal membrane oxygenation, renal replacement therapy, cardiopulmonary resuscitation, and necrotizing enterocolitis) and were matched with a control patient on criteria of procedure, diagnosis, and age who experienced no such event. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of a total 536 bypass operations in the study period, 38 patients experienced one of the defined events. Twenty-eight cases were included in the study after removing patients who suffered an event after 72 hours or who had insufficient data. Clinical and laboratory data were collected to derive scores for the first 12 hours after surgery. The inadequate oxygen delivery index was calculated by Etiometry using vital signs and laboratory data. A modified Low Cardiac Output Syndrome Score was calculated from clinical and therapeutic markers. The mean inadequate oxygen delivery and modified Low Cardiac Output Syndrome Score were compared within each matched pair using the Wilcoxon signed-rank test. Inadequate oxygen delivery correctly differentiated adverse events in 13 of 28 matched pairs, with no evidence of inadequate oxygen delivery being higher in cases (p = 0.71). Modified Low Cardiac Output Syndrome Score correctly differentiated adverse events in 23 of 28 matched pairs, with strong evidence of a raised score in low cardiac output syndrome cases (p < 0.01). CONCLUSIONS: Although inadequate oxygen delivery is an Food and Drug Administration approved indicator of risk for low mixed venous oxygen saturation, early postoperative average values were not linked with medium-term adverse events. The indicators included in the modified Low Cardiac Output Syndrome Score had a much stronger association with the specified adverse events.

The Effect of Acetaminophen on Temperature in Critically Ill Children: A Retrospective Analysis of Over 50,000 Doses.

OBJECTIVES: Acetaminophen is widely used in PICUs. Although randomized controlled trials suggest that acetaminophen significantly reduces body temperature in adults, the effect of acetaminophen on temperature in critically ill children has not been previously quantified. DESIGN: Retrospective observational cohort study. SETTING: Single-center general and cardiac PICU in a specialist children's hospital. PATIENTS: All children who received acetaminophen or had a fever (temperature ≥ 38°C) while on the ICU over a 40-month period (September 2012 to December 2015). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 58,177 doses of acetaminophen were administered, with temperature data available for analysis for 54,084 doses. Temperature decreased by 0.11°C (95% CI, 0.09-0.14°C) 4 hours post acetaminophen dose, after adjustment for weight and illness severity. In children who had a fever and were given acetaminophen, temperature decreased by 0.78°C (95% CI, 0.74-0.82°C). Temperature decreased by 0.88°C (95% CI, 0.85-0.92°C) in children who had fever but did not receive acetaminophen. The change in temperature associated with fever was significantly different between those who did and did not receive acetaminophen (likelihood ratio statistic 246.06; p < 2.2 × 10(-16)). CONCLUSIONS: Acetaminophen is associated with a significant decrease in temperature in children with fever. However, temperature may decrease following fever without acetaminophen in the PICU. The threshold to use acetaminophen must be understood to determine the true effect on temperature in any future trials.

Randomized Study of Early Continuous Positive Airways Pressure in Acute Respiratory Failure in Children With Impaired Immunity (SCARF) ISRCTN82853500.

OBJECTIVES: Previous trials in adults with impaired immunity and respiratory failure suggest that early noninvasive ventilation avoids endotracheal intubation and improves survival. No randomized clinical trials have addressed this question in children. DESIGN: We undertook an open, parallel-group randomized trial in three pediatric hospitals. SUBJECTS: Children with impaired immunity and acute respiratory failure defined as tachypnoea (> 90th centile); a new requirement for supplemental oxygen; and new chest radiograph infiltrates. INTERVENTIONS: Children were randomly assigned to early PICU admission for continuous positive airways pressure (early continuous positive airways pressure) or to standard care. The primary outcome was endotracheal intubation by 30 days. MEASUREMENTS AND MAIN RESULTS: One-hundred fourteen children met inclusion criteria of whom 42 were randomized between January 2013 and January 2016. There was no significant difference in endotracheal intubation by 30 days with early continuous positive airways pressure (10/21; 48%) compared with standard care (5/21; 24%), odds ratio 2.9 (0.8-10.9), p value equals to 0.11. However, 30-day mortality was significantly higher with early continuous positive airways pressure (7/21; 33%) compared with standard care (1/21; 5%), odds ratio 10.0 (1.1-90.6), p value equals to 0.041. Mortality at 90 days was early continuous positive airways pressure (11/21; 52%) versus standard care (4/21; 19%), odds ratio 4.7 (1.2-18.6), p value equals to 0.029, whereas mortality at 1 year was similar early continuous positive airways pressure (13/21; 61.9%) versus standard care (9/21; 42.7%), odds ratio 2.2 (0.6-7.4), p value equals to 0.22. There were two serious adverse events: early continuous positive airways pressure (pneumothorax) and standard care (hemothorax). CONCLUSIONS: This study provided no evidence to support early PICU admission for continuous positive airways pressure in children with acute respiratory failure and impaired immunity. There was a trend toward increased endotracheal intubation and a higher early mortality in the early continuous positive airways pressure group.

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.

PaO2/FIO2 Ratio Derived From the SpO2/FIO2 Ratio to Improve Mortality Prediction Using the Pediatric Index of Mortality-3 Score in Transported Intensive Care Admissions.

OBJECTIVES: To derive a relationship between the SpO2/FIO2 ratio and PaO2/FIO2 ratio across the entire range of SpO2 values (0-100%) and to evaluate whether mortality prediction using the Pediatric Index of Mortality-3 can be improved by the use of PaO2/FIO2 values derived from SpO2/FIO2. DESIGN: Retrospective analysis of prospectively collected data. SETTING: A regional PICU transport service. PATIENTS: Children transported to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The relationship between SpO2/FIO2 and PaO2/FIO2 across the entire range of SpO2 values was first studied using several mathematical models in a derivation cohort (n = 1,235) and then validated in a separate cohort (n = 306). The best SpO2/FIO2-PaO2/FIO2 relationship was chosen according to the ability to detect respiratory failure (PaO2/FIO2 ≤ 200). The discrimination of the original Pediatric Index of Mortality-3 score and a derived Pediatric Index of Mortality-3 score (where SpO2/FIO2-derived PaO2/FIO2 values were used in place of missing PaO2/FIO2 values) were compared in a different cohort (n = 1,205). The best SpO2/FIO2-PaO2/FIO2 relationship in 1,703 SpO2/FIO2-to-PaO2/FIO2 data pairs was a linear regression equation of ln[PF] regressed on ln[SF]. This equation identified children with a PaO2/FIO2 less than or equal to 200 with a specificity of 73% and sensitivity of 61% in children with SpO2 less than 97% (92% and 33%, respectively, when SpO2 ≥ 97%) in the validation cohort. PaO2/FIO2 derived from SpO2/FIO2 (derived PaO2/FIO2) was better at predicting PICU mortality (area under receiver operating characteristic curve, 0.64; 95% CI, 0.55-0.73) compared with the original PaO2/FIO2 (area under receiver operating characteristic curve, 0.54; 95% CI, 0.49-0.59; p = 0.02). However, there was no difference in the original and derived Pediatric Index of Mortality-3 scores and their discriminatory ability for mortality. CONCLUSIONS: SpO2-based metrics perform no worse than arterial blood gas-based metrics in mortality prediction models. Future Pediatric Index of Mortality score versions may be improved by the inclusion of risk factors based on oxygen saturation values, especially in settings where PaO2 values are missing in a significant proportion of cases.

Admission PaO2 and Mortality in Critically Ill Children: A Cohort Study and Systematic Review.

OBJECTIVE: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. DESIGN: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: "hyperoxia," "hypoxia," "critically ill children," "pediatric intensive care," "mortality," and/or "survival." SETTING: Tertiary PICU. PATIENTS: Patients younger than 18 years of age. INTERVENTIONS: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, < 60 torr [8 kPa] or peripheral oxygen saturations, < 90%) to mortality in critically ill children was explored. MEASUREMENTS AND MAIN RESULTS: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group (< 8 kPa) to 5.3% (287/5,385) with normoxia and 9.1% (64/701) in the hyperoxic group (> 40 kPa). Nonlinear regression displayed a "U-shaped" relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79-5.48; p < 0.001) compared to normoxia. Six studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality compared to normoxia (odds ratio, 1.15; 95% CI, 0.42-3.17; p = 0.77). CONCLUSIONS: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.