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.

Fifteen-minute consultation: Point of care ultrasound in the management of paediatric shock.

The use of point of care ultrasound (POCUS) in the assessment of the acutely shocked adult patient has been well established for over a decade. Comparatively, its use in paediatrics has been limited, but this is starting to change with the recent introduction of Children's Acute Ultrasound training. This article highlights the pathophysiology of shock in children and demonstrates how bedside ultrasound can be used to assist decision making in the clinical assessment of the neonate, infant or older child presenting with undifferentiated shock. We discuss a structured protocol to use when performing the POCUS examination and explain how this could lead to a more rapid correlation of the ultrasound findings with the underlying cause of shock.

Fifteen-minute consultation: Using point of care ultrasound to assess children with respiratory failure.

Point of care ultrasound (POCUS) is well established in adult emergency medicine and critical care. It is used for immediate diagnosis and evaluation of the impact of bedside interventions in the acutely unwell child. This article highlights how ultrasound can be helpful in paediatric practice when dealing with the neonate, infant or older child with undifferentiated respiratory distress, respiratory failure or ventilation problems. It highlights indications for use, key diagnostic features of common pathology and outlines the benefits of POCUS in everyday practice.

Preoperative bioelectrical impedance predicts intensive care length of stay in children following cardiac surgery.

We have previously shown that children with a bioelectrical impedance spectroscopy phase angle at 50° (PA 50°) of <2.7 on postoperative day 2 had a four-fold increase in the risk of prolonged paediatric intensive care length of stay. In this study, we demonstrate a relationship between a baseline measure of phase angle 200/5° and postoperative length of stay.

Accuracy of the Masimo SET® LNCS neo peripheral pulse oximeter in cyanotic congenital heart disease.

UNLABELLED: Introduction Non-invasive peripheral pulse oximeters are routinely used to measure oxyhaemoglobin saturation (SpO2) in cyanotic congenital heart disease. These probes are calibrated in healthy adult volunteers between arterial saturations of ~75 and 100%, using the gold standard of co-oximetry on arterial blood samples. There are little data to attest their accuracy in cyanotic congenital heart disease. Aims We aimed to assess the accuracy of a commonly used probe in children with cyanotic congenital heart disease. METHODS: Children with cyanotic congenital heart disease admitted to the Paediatric Intensive Care Unit with an arterial line in situ were included to our study. Prospective simultaneous recordings of SpO2, measured by the Masimo SET® LNCS Neo peripheral probe, and co-oximeter saturations (SaO2) measured by arterial blood gas analysis were recorded. RESULTS: A total of 527 paired measurements of SpO2 and SaO2 (using an ABL800 FLEX analyser) in 25 children were obtained. The mean bias of the pulse oximeter for all SaO2 readings was +4.7±13.8%. The wide standard deviation indicates poor precision. This mean bias increased to +7.0±13.7% at SaO2 recordings <75%. The accuracy root mean square of the recordings was 3.30% across all saturation levels, and this increased to 4.98% at SaO2 <75%. CONCLUSIONS: The performance of the Masimo SET® LNCS Neo pulse oximeter is poor when arterial oxyhaemoglobin saturations are below 75%. It tends to overestimate saturations in children with cyanotic congenital heart disease. This may have serious implications for clinical decisions.

Short-term renal support in postoperative repair of tetralogy of Fallot in the paediatric intensive care unit: can we predict those who need it?

INTRODUCTION: Fluid balance and renal function can be difficult to manage in the postoperative infant with tetralogy of Fallot. High fluid volumes are often needed to maintain cardiac output. Aims To stratify patients at risk for advanced renal support following tetralogy of Fallot repair. METHODS: Retrospective analysis of all consecutive tetralogy of Fallot cases operated at a single centre in a 3-year period. RESULTS: A total of 41 children were identified. All cases had loop diuretics administered. Of the cases, 17% required support with a peritoneal dialysis catheter, with only one complication of peritoneal dialysis catheter blockage. The mean length of paediatric intensive care unit stay in those receiving peritoneal dialysis catheter insertion was prolonged by an additional mean of 6 days (p<0.001). No statistical significance was found between those children requiring peritoneal dialysis and those who did not when considering patient age and weight at time of repair, cardiopulmonary bypass and aortic cross clamp times, the presence of a transannular patch, or junctional ectopic tachycardia. However, volume requirement of more than 35 ml/kg in the first 12 hours following repair did increase the likelihood to need peritoneal dialysis (p<0.0001). Furthermore, the higher the peak creatinine, the longer the stay on intensive care (p<0.01). CONCLUSIONS: Peritoneal dialysis is an effective method of dealing with fluid balance in children after tetralogy of Fallot repair, with minimal complications. Early consideration should be given to peritoneal dialysis when it is clear that high fluid volumes are required postoperatively.

Twelve tips for teaching with ultrasound in the undergraduate curriculum.

With ever increasing use of imaging as a diagnostic tool in medicine, medical schools are being urged to further integrate imaging into their curricula. Ultrasound is one such way of doing so-enabling students to bridge the gap between form and function, medical school and clinical practice. As a non-invasive imaging technique, with low risk when compared to other methods of imaging, ultrasound is ideal for integration into basic science and clinical teaching. The twelve tips given in this article offer advice on the practicalities of running a successful ultrasound imaging session in an appropriate environment, promoting safety and curriculum integration.

15-minute consultation: a structured approach to the assessment of chest pain in a child.

This article aims to provide a concise, structured approach to the child with chest pain. Chest pain is a common presenting symptom in children but, unlike in adults, the cause is rarely cardiac. We review the main causes of chest pain in children and discuss the important features that may alert those assessing paediatric chest pain to serious underlying pathology. In the vast majority of cases, reassurance is all that is required and a thorough initial consultation can exclude rare, serious disease and provide vital reassurance to children and families.

Development of the Children's ACuTe UltraSound (CACTUS) point-of-care ultrasound (POCUS)-accredited training in the UK: a descriptive study.

Point-of-care ultrasound (POCUS) is an established, evidence-supported tool that can be used in neonatal and paediatric medicine, offering clinicians immediate diagnostic insights, assessment of interventions and improved safety profiles and success rate of various procedures. Its effective use requires an established education programme, governance and standardisation to ensure competence in this skill. While adult clinical practice has established POCUS training protocols, this had not been replicated in paediatrics. This article describes the development and launch of the UK's inaugural accredited paediatric-specific POCUS curriculum and training pathway: the 'Children's ACuTe UltraSound' course, addressing this significant gap in paediatric healthcare education and describing the training delivered and available for paediatricians and allied health professionals working with children.

Point-of-care ultrasound as a diagnostic tool in respiratory assessment in awake paediatric patients: a comparative study.

BACKGROUND: Chest X-ray (CXR) has typically been the main investigation in children with suspected respiratory pathology. Recent advances in lung point-of-care ultrasound (POCUS) have shown the potential for it to be comparative, if not better, than CXR. The objective of this study was to compare CXR with lung POCUS in children with respiratory illness in a ward-based setting at a paediatric teaching hospital. METHODS: Any child <18 years of age presenting to Southampton Children's Hospital requiring a CXR for clinical reasons also had lung POCUS performed. CXR was reported by a consultant paediatric radiologist and lung POCUS was reviewed retrospectively by a blinded POCUS clinician, with only the clinical information provided on the CXR request. Comparisons were made between the CXR and lung POCUS findings. RESULTS: 100 paired lung POCUS and CXR were included in the study. 30% of lung POCUS were normal with 97% of these having a normal CXR. 70% of cases had POCUS abnormalities with 96% of POCUS cases identifying comparative lung pathology. Lung POCUS therefore had a sensitivity of 98.51% and a specificity of 87.9% with a diagnostic accuracy of 95% when compared with the CXR report. CONCLUSIONS: Lung POCUS has excellent diagnostic accuracy. The diagnosis of normal lung on POCUS when performed by a trained practitioner can reliably reduce the need for a CXR, thus reducing CXR use and radiation exposure in children. An abnormal lung POCUS could then either give the diagnosis or lead to a CXR with the expectation of clinically relevant findings.

Can critical care transport be safely reduced in children intubated during emergency management of status epilepticus in the United Kingdom: a national audit with case-control analysis.

OBJECTIVE: This study describes the baseline clinical characteristics, predictors of successful extubation at referring hospitals and short-term outcomes of children intubated for status epilepticus and referred to United Kingdom (UK) paediatric critical care transport teams (PCCTs). DESIGN: Multicentre audit with case-control analysis, conducted between 1 September 2018 and 1 September 2020. SETTING: This study involved 10 UK PCCTs. PATIENTS: Children over 1 month of age intubated during emergency management for status epilepticus (SE), referred to UK PCCTs. Patients with trauma, requiring time-critical neurosurgical intervention or those with a tracheostomy were excluded. INTERVENTIONS: No interventions were implemented. MEASUREMENTS AND MAIN RESULTS: Out of the 1622 referrals for SE, 1136 (70%) were intubated at referral. The median age was 3 years (IQR 1.25-6.54 years). Among the intubated children, 396 (34.8%) were extubated locally by the referring team, with 19 (4.8%) requiring reintubation. Therefore, the overall rate of successful extubation was 33% (377/1136). There was significant variation between PCCTs, with local extubation rates ranging from 2% to 74%. Multivariable analyses showed region/PCCT, contributing diagnosis, acute changes on CT, preceding encephalopathy and type of continuous sedation (midazolam) used postintubation were significantly associated with transfer to a critical care unit. CONCLUSION: This study highlights wide regional variation in early extubation practices. Regions with high successful extubation rates have established extubation guidelines from PCCTs. Successful extubation represents critical care transports that have been avoided.

Implantable cardioverter defibrillator therapy in paediatric practice: a single-centre UK experience with focus on subcutaneous defibrillation.

AIMS: Sudden cardiac death (SCD) risk can be managed by implantable cardioverter defibrillators (ICD). Defibrillation shocks can be delivered via ICD generator and/or intracardiac or subcutaneous coil configurations. We present our single-centre use of childhood ICDs. METHODS AND RESULTS: Twenty-three patients had ICD implantation, with median age and weight of 12.96 years and 41.35 kg. Indications included eight long QT; four hypertrophic cardiomyopathy; three Brugada syndrome; two idiopathic ventricular fibrillation; two post-congenital heart repair; two family history of SCD with abnormal repolarization; one catecholaminergic polymorphic ventricular tachycardia; and one left ventricle non-compaction. Twelve had out of hospital cardiac arrests prior to implantation. Techniques included 13 conventional ICD implants (pre-pectoral device with endocardial leads), 7 with subcutaneous defibrillation coils (sensing via epicardial or endocardial leads tunnelled to the ICD), and 3 with exclusive subcutaneous ICD (sensing and defibrillation via the same subcutaneous lead). Satisfactory defibrillation efficacy and ventricular arrhythmia sensing was confirmed at implantation. Follow-up ranged from 0.17 to 11.08 years. One child died with the ICD in situ. Ten children received appropriate shocks; five on more than one occasion. Five received inappropriate shocks (for inappropriate recognition of sinus tachycardia or supraventricular tachycardia). Five children underwent six further interventions; all had intracardiac leads. CONCLUSION: Innovative shock delivery systems can be used in children requiring an ICD. The insertion technique and device used need to accommodate the age and weight of the child, and concomitant need for pacing therapy. We have demonstrated effective defibrillation with shocks delivered via configurations employing subcutaneous coils in children.

Management of tetralogy of Fallot in the pediatric intensive care unit.

Tetralogy of Fallot (ToF) is one of the most common congenital cyanotic heart lesions and can present to a variety of health care professionals, including teams working in pediatric intensive care. Pediatric intensive care teams may care for a child with ToF pre-operatively, peri-operatively, and post-operatively. Each stage of management presents its own unique challenges. In this paper we discuss the role of pediatric intensive care in each stage of management.

Psychological impact of working in paediatric intensive care. A UK-wide prevalence study.

OBJECTIVE: To determine the prevalence of work-related psychological distress in staff working in UK paediatric intensive care units (PICU). DESIGN: Online (Qualtrics) staff questionnaire, conducted April to May 2018. SETTING: Staff working in 29 PICUs and 10 PICU transport services were invited to participate. PARTICIPANTS: 1656 staff completed the survey: 1194 nurses, 270 physicians and 192 others. 234 (14%) respondents were male. Median age was 35 (IQR 28-44). MAIN OUTCOME MEASURES: The Moral Distress Scale-Revised (MDS-R) was used to look at moral distress, the abbreviated Maslach Burnout Inventory to examine the depersonalisation and emotional exhaustion domains of burnout, and the Trauma Screening Questionnaire (TSQ) to assess risk of post-traumatic stress disorder (PTSD). RESULTS: 435/1194 (36%) nurses, 48/270 (18%) physicians and 19/192 (10%) other staff scored above the study threshold for moral distress (≥90 on MDS-R) (χ2 test, p<0.00001). 594/1194 (50%) nurses, 99/270 (37%) physicians and 86/192 (45%) other staff had high burnout scores (χ2 test, p=0.0004). 366/1194 (31%) nurses, 42/270 (16%) physicians and 21/192 (11%) other staff scored at risk for PTSD (χ2 test, p<0.00001). Junior nurses were at highest risk of moral distress and PTSD, and junior doctors of burnout. Larger unit size was associated with higher MDS-R, burnout and TSQ scores. CONCLUSIONS: These results suggest that UK PICU staff are experiencing work-related distress. Further studies are needed to understand causation and to develop strategies for prevention and treatment.

The role of point-of-care ultrasound in pediatric acute respiratory distress syndrome: emerging evidence for its use.

Pediatric acute respiratory distress syndrome (PARDS) remains an important cause of significant morbidity and mortality. The 2015 PALICC definition of PARDS requires chest imaging to diagnose the presence of new pulmonary infiltrate(s). Traditionally chest radiography or computerised tomography have been used. However, these carry the limitations of exposure to ionizing radiation, need to transfer the critically unwell child, lag-time with clinical correlation and lack of immediate results. The use of point of care ultrasound (POCUS) has been well established in adult emergency medicine and critical care. Furthermore, the adult literature clearly demonstrates that lung POCUS is a safe and validated tool, which is highly sensitive and specific when compared to chest radiography for differentiating the causes of respiratory failure, including ARDS. Whilst pediatric specific data is limited, it has been shown that the signs seen in adults are reproducible in critically ill neonates and children. Furthermore, the numerous benefits of POCUS in the paediatric setting are compelling and include lack of ionizing radiation, immediate feedback, promoting time at the bedside of the critically unwell child, and ease of serial assessments. This review article presents the emerging evidence demonstrating that lung POCUS can be used not only to support the diagnosis of pediatric ARDS, but also to assess for complications, monitor progression and thus guide management. We hope it will stimulate much needed collaborative research into this exciting field of imaging and its applications to PARDS and beyond.

Impact of child death on paediatric trainees.

OBJECTIVE: To assess the prevalence of symptoms of acute stress reactions (ASR) and post-traumatic stress disorder (PTSD) in paediatric trainees following their involvement in child death. DESIGN: A survey designed to identify trainees' previous experiences of child death combined with questions to identify features of PTSD. Quantitative interpretation was used alongside a χ2 test. A p value of <0.05 was considered significant. SETTING: 604 surveys were distributed across 13 UK health education deaneries. PARTICIPANTS: 303/604 (50%) of trainees completed the surveys. RESULTS: 251/280 (90%) of trainees had been involved with the death of a child, although 190/284 (67%) had no training in child death. 118/248 (48%) of trainees were given a formal debrief session following their most recent experience. 203/251 (81%) of trainees reported one or more symptoms or behaviours that could contribute to a diagnosis of ASR/PTSD. 23/251 (9%) of trainees met the complete criteria for ASR and 13/251 (5%) for PTSD. Attending a formal debrief and reporting feelings of guilt were associated with an increase in diagnostic criteria for ASR/PTSD (p=0.036 and p<0.001, respectively). CONCLUSIONS: Paediatric trainees are at risk of developing ASR and PTSD following the death of a child. The feeling of guilt should be identified and acknowledged to allow prompt signposting to further support, including psychological assessment or intervention if required. Clear recommendations need to be made about the safety of debriefing sessions as, in keeping with existing evidence, our data suggest that debrief after the death of a child may be associated with the development of symptoms suggestive of ASR/PTSD.

Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial.

BACKGROUND: Oxygen saturation monitoring for children receiving respiratory support is standard worldwide. No randomised clinical trials have compared peripheral oxygen saturation (SpO2) targets for critically ill children. The harm of interventions to raise SpO2 to > 94% may exceed their benefits. METHODS: We undertook an open, parallel-group randomised trial of children > 38 weeks completed gestation and < 16 years of age receiving invasive or non-invasive respiratory support and supplemental oxygen who were admitted urgently to one of three paediatric intensive care units. A 'research without prior consent' approach was employed. Children were randomly assigned to a liberal oxygenation group (SpO2 targets > 94%) or a conservative oxygenation group (SpO2 = 88-92% inclusive). Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between-group separation of SpO2 and safety. The Oxy-PICU trial was registered before recruitment: ClinicalTrials.gov identifier NCT03040570. RESULTS: A total of 159 children met the inclusion criteria, of whom 119 (75%) were randomised between April and July 2017, representing a rate of 10 patients per month per site. The mean time to randomisation from first contact with an intensive care team was 1.9 (SD 2.2) h. Consent to continue in the study was obtained in 107 cases (90%); the children's parents/legal representatives were supportive of the consent process. The median (interquartile range, IQR) of time-weighted individual mean SpO2 was 94.9% (92.6-97.1) in the conservative oxygenation group and 97.5% (96.2-98.4) in the liberal group [difference 2.7%, 95% confidence interval (95% CI) 1.3-4.0%, p < 0.001]. Median (IQR) time-weighted individual mean FiO2 was 0.28 (0.24-0.37) in the conservative group and 0.37 (0.30-0.42) in the liberal group (difference 0.08, 95% CI 0.03-0.13, p < 0.001). There were no significant between-group differences in length of stay, duration of organ support or mortality. Two prespecified serious adverse events (cardiac arrests) occurred, both in the liberal oxygenation group. CONCLUSION: A definitive clinical trial of peripheral oxygen saturation targets is feasible in critically ill children.

The Accuracy of Noninvasive Peripheral Pulse Oximetry After Palliative Cardiac Surgery in Patients With Cyanotic Congenital Heart Disease.

BACKGROUND: Children with cyanotic congenital heart disease (CCHD) live with oxyhemoglobin saturations that are typically expressed as percentages in the range of 70s and 80s. Peripheral pulse oximetry (measurement of SpO2) performs poorly in this range and yet is widely used to inform clinical decisions in these patients. The reference standard is co-oximetry of arterial samples (SaO2). METHODS: In this study, 515 paired measurements of SpO2 and SaO2 were taken from 19 children who had undergone palliative cardiac surgery. RESULTS: SpO2 (Masimo SET LNCS Neo pulse oximeter) overestimated oxyhemoglobin saturation in 82% of measurements (mean 4.6% ± 6.6%). There was a strong negative correlation between mean bias and SaO2 ( r = -.96, P = .002, 95% confidence interval: -0.99 to -0.68). CONCLUSION: The results raise a concern that critical hypoxemia may go undetected and untreated if pulse oximetry is relied upon as the primary means of assessing oxyhemoglobin saturation in children with CCHD. Strong preference must be given to co-oximetry of arterial samples.

Protocol for a randomised pilot multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU).

INTRODUCTION: Optimal targets for systemic oxygenation in paediatric critical illness are unknown. Observational data indicate that high levels of arterial oxygenation are associated with poor outcomes in resuscitation of the newborn and in adult critical illness. Within paediatric intensive care units (PICUs), staff prevent severe hypoxia wherever possible, but beyond this there is no consensus. Practice varies widely with age, diagnosis, treating doctor and local or national guidelines followed, though peripheral blood oxygen saturations (SpO2) of >95% are often targeted. The overall aim of this pilot study is to determine the feasibility of performing a randomised trial in critically ill children comparing current practice of liberal SpO2 targets with a more conservative target. METHODS AND ANALYSIS: Oxy-PICU is a pragmatic, open, pilot randomised controlled trial in infants and children requiring mechanical ventilation and receiving supplemental oxygen for abnormal gas exchange accepted for emergency admission to one of three participating UK PICUs. The study groups will be either a conservative SpO2 target of 88%-92% (inclusive) or a liberal SpO2 target of >94%. Infants and children who fulfil all inclusion criteria and none of the exclusion criteria will be randomised 1:1 by a secure web-based system to one of the two groups. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support. Discharge outcomes will also be recorded. In addition to observational data, blood and urine samples will be taken to identify biochemical markers of oxidative stress. Outcomes are targeted at assessing study feasibility with a primary outcome of adequate study recruitment (target: 120 participants). ETHICS AND DISSEMINATION: The trial received Health Research Authority approval on 1 June 2017 (16/SC/0617). Study findings will be disseminated in national and international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03040570.