Peri‐operative cardiac arrest in children as reported to the 7th National Audit Project of the Royal College of Anaesthetists

The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest. An activity survey estimated UK paediatric anaesthesia annual caseload as 390,000 cases, 14% of the UK total. Paediatric peri‐operative cardiac arrests accounted for 104 (12%) reports giving an incidence of 3 in 10,000 anaesthetics (95%CI 2.2–3.3 per 10,000). The incidence of peri‐operative cardiac arrest was highest in neonates (27, 26%), infants (36, 35%) and children with congenital heart disease (44, 42%) and most reports were from tertiary centres (88, 85%). Frequent precipitants of cardiac arrest in non‐cardiac surgery included: severe hypoxaemia (20, 22%); bradycardia (10, 11%); and major haemorrhage (9, 8%). Cardiac tamponade and isolated severe hypotension featured prominently as causes of cardiac arrest in children undergoing cardiac surgery or cardiological procedures. Themes identified at review included: inappropriate choices and doses of anaesthetic drugs for intravenous induction; bradycardias associated with high concentrations of volatile anaesthetic agent or airway manipulation; use of atropine in the place of adrenaline; and inadequate monitoring. Overall quality of care was judged by the panel to be good in 64 (62%) cases, which compares favourably with adults (371, 52%). The study provides insight into paediatric anaesthetic practice, complications and peri‐operative cardiac arrest

Eliciting the experiences of the adolescent-parent dyad following critical care admission: a pilot study

Critically ill adolescents are usually treated on intensive care units optimised for much older adults or younger children. The way they access and experience health services may be very different to most adolescent service users, and existing quality criteria may not apply to them. The objectives of this pilot study were, firstly, to determine whether adolescents and their families were able to articulate their experiences of their critical care admission and secondly, to identify the factors that are important to them during their intensive care unit (ICU) or high dependency unit (HDU) stay. Participants were 14–17 year olds who had previously had an emergency admission to an adult or paediatric ICU/HDU in one of four UK hospitals (two adult, two paediatric) and their parents. Semi-structured interviews were conducted with eight mother-adolescent dyads and one mother. Interviews were transcribed and analysed using framework analysis. Conclusion: The main reported determinant of high-quality care was the quality of interaction with staff. The significance of these interactions and their environment depended on adolescents’ awareness of their surroundings, which was often limited in ICU and changed significantly over the course of their illness. Qualitative interview methodology would be difficult to scale up for this group

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 (SpO_{2}) targets for critically ill children. The harm of interventions to raise SpO_{2} to > 94% may exceed their benefits. METHODS: We undertook an open, parallel-group randomised trial of children > 38 weeks completed gestation and  94%) or a conservative oxygenation group (SpO_{2} = 88–92% inclusive). Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between-group separation of SpO_{2} 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 SpO_{2} 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 FiO_{2} 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

Fluorene-based fluorescent probes with high two-photon action cross-sections for biological multiphoton imaging applications

Two-photon fluorescence microscopy is a powerful tool for the study of dynamic cellular processes and live-cell imaging. Many commercially available fluorescent probes have been used in multiphoton-based imaging studies despite exhibiting relatively low two-photon absorption cross-section values in the tunability range of ultrafast Ti:sapphire lasers commonly used in multiphoton microscopy imaging. Furthermore, available fluorophores may be plagued with low fluorescence quantum yield and/or photoinstability (i.e., photobleaching) on exposure to the high peak power and photon density provided by the ultrafast laser source. To address the demand for better performing dyes, we prepare fluorophores tailored for multiphoton imaging. These fluorophores are based on the fluorene ring system, known to exhibit high fluorescence quantum yield ( \u3e 0.7) and high photostability. Furthermore, an amine-reactive fluorescent probe for the covalent attachment onto amine-containing biomolecules is also prepared. Epi-fluorescence and two-photon fluorescence microscopy images of H9c2 rat cardiomyoblasts stained with an efficient two-photon absorbing fluorene fluorophore is demonstrated. Additionally, single-photon spectral characteristics of the amine-reactive fluorophore, as well as the two-photon absorption cross sections of its model adduct in solution, and spectral characterization of a bovine serum albumin (BSA) as a model bioconjugate are presented

Mechanical power in pediatric acute respiratory distress syndrome:a PARDIE study

BACKGROUND: Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS). METHODS: Retrospective analysis of a prospective observational international cohort study. RESULTS: There were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure—positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min(−1)·Kg(−1) Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min(−1)·Kg(−1) OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min(−1)·Kg(−1) OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min(−1)·Kg(−1) SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO(2) than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD. CONCLUSIONS: Higher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation. Take Home Message: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-021-03853-6

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Paediatric 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 (Spo2) 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 Spo2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Spo2 target of more than 94% or a conservative Spo2 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

The 7th National Audit Project (NAP7) baseline survey of individual anaesthetists: preparedness for and experiences of peri-operative cardiac arrest

The Royal College of Anaesthetists' 7th National Audit Project baseline survey assessed knowledge, attitudes, practices and experiences of peri-operative cardiac arrests among UK anaesthetists and Anaesthesia Associates. We received 10,746 responses, representing a 71% response rate. In-date training in adult and paediatric advanced life support was reported by 9646 (90%) and 7125 (66%) anaesthetists, respectively. There were 8994 (84%) respondents who were confident in leading a peri-operative cardiac arrest, with males more confident than females, but only 5985 (56%) were confident in leading a debrief and 7340 (68%) communicating with next of kin. In the previous two years, 4806 (46%) respondents had managed at least one peri-operative cardiac arrest, of which 321 (7%) and 189 (4%) of these events involved a child or an obstetric patient, respectively. Respondents estimated the most common causes of peri-operative cardiac arrest to be hypovolaemia, hypoxaemia and cardiac ischaemia, with haemorrhage coming fifth. However, the most common reported causes for the most recently attended peri-operative cardiac arrest were haemorrhage; (927, 20%); anaphylaxis (474, 10%); and cardiac ischaemia (397, 9%). Operating lists or shifts were paused or stopped after 1330 (39%) cardiac arrests and 1693 (38%) respondents attended a debrief, with ‘hot’ debriefs most common. Informal wellbeing support was relatively common (2458, 56%) and formal support was uncommon (472, 11%). An impact on future care delivery was reported by 196 (4%) anaesthetists, most commonly a negative psychological impact. Management of a peri-operative cardiac arrest during their career was reported by 8654 (85%) respondents. The overall impact on professional life was more often judged positive (2630, 30%) than negative (1961, 23%), but impact on personal life was more often negative

A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial.

BACKGROUND: Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. OBJECTIVES: This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. DESIGN: Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. SETTING: The setting was 13 English PICUs. PARTICIPANTS: Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). INTERVENTION: The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. CONVENTIONAL MANAGEMENT (CM): This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. MAIN OUTCOME MEASURES: The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. RESULTS: CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) -0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs -£3620, 95% CI -£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost -£9865, 95% CI -£18,558 to -£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI -£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI -£11,203 to £17,894), but close to zero for the cardiac surgery stratum (-£919, 95% CI -£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI -£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. CONCLUSIONS: CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61735247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information