Marzena Orzol

Objective: Providing adequate nutrition is a key aspect of pediatric intensive care, with enteral administration preferred. The regular measurement of gastric residual volume (GRV) to guide feeding is common, but it results in frequent feed interruptions due to a perceived high GRV. The GASTRIC-PICU (GRV to guide enteral feeding vs. routine measurement in mechanically ventilated critically ill children) randomized controlled trial aims to evaluate the clinical and cost-effectiveness of not routinely measuring GRV to guide enteral feeding compared with the usual practice of routine measurement. Design: Multicenter, randomized, non-inferiority, open-label clinical trial with embedded health economic evaluation. Setting: Twenty-three PICUs across United Kingdom, Scotland, Northern Ireland, and Switzerland. Patients: Infants and children 37 weeks old or older corrected gestational age to 16 years admitted to participating PICUs, on mechanical ventilation and being enterally fed. Intervention and Comparison: Standard feeding protocols without routinely measuring GRV to guide feeding will be compared against standard feeding protocols with routine (at least 6-hourly) GRV measurement to guide feeding. Measurements and Main Results: Randomization 1:1 between no routine GRV measurement and routine GRV measurement stratified by site, age at admission, and main reason for admission. “Research Without Prior Consent” will be used. The primary clinical outcome is a composite outcome of survival and days free from mechanical ventilation at 30 days (non-inferiority). The superiority co-primary outcome is the percentage of the child’s estimated energy requirements achieved by 72 hours after randomization. The primary outcome of cost-effectiveness analysis is incremental net monetary benefits at 6 months. Baseline demographics and clinical status, daily nutritional data for the first 7 days, and discharge outcome, as well as longer-term survival and economic data will be collected. Conclusions: Trial findings will be disseminated in peer reviewed journals, via international conferences and in lay language via social media.

Background: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practised but is associated with harm in observational studies. Objectives: To evaluate the clinical and cost-effectiveness of a conservative oxygenation target of peripheral oxygen saturation 88–92% compared with peripheral oxygen saturation > 94% in critically ill children admitted to paediatric intensive care unit as an emergency. Design and setting: A pragmatic, open, multicentre, parallel-group, randomised clinical trial conducted in 15 National Health Service paediatric intensive care units and associated emergency transport services across England and Scotland. Participants: Children aged > 38 weeks corrected gestational age and < 16 years, enrolled within 6 hours of being accepted for admission to paediatric intensive care unit as an emergency; receiving invasive mechanical ventilation with supplemental oxygen; and in face-to-face contact with paediatric intensive care unit or emergency transport services staff. Interventions: Adjustment of ventilator and inspired oxygen settings aiming to achieve peripheral oxygen saturation 88–92% (conservative oxygenation) or peripheral oxygen saturation > 94% (liberal oxygenation) during invasive mechanical ventilation. Main outcome measures: Primary outcomes: duration of organ support at 30 days, with death by day 30 ranked as the worst outcome (clinical effectiveness) and incremental costs, quality-adjusted life-years and net monetary benefit at 12 months (cost-effectiveness). Secondary outcomes: incremental costs at 30 days; mortality at paediatric intensive care unit discharge, 30 days, 90 days and 12 months; time to liberation from ventilation; duration of organ support; length of paediatric intensive care unit and hospital stay; functional status at paediatric intensive care unit discharge; and health-related quality of life at 12 months. Results: Two thousand and forty children were randomised between 1 September 2020 and 15 May 2022. Consent was obtained for 1872 (94%) – 939 to the conservative and 933 to the liberal oxygenation group – who were included in the primary analysis. Duration of organ support or death in the first 30 days was lower in the conservative oxygenation group [probabilistic index 0.53, 95% confidence interval 0.50 to 0.55; p = 0.04 Wilcoxon rank-sum test, adjusted odds ratio 0.84 (95% confidence interval 0.72 to 0.99)]. Both components of the composite primary outcome and secondary outcomes favoured conservative oxygenation. Average costs at 30 days strongly indicated lower costs with conservative oxygenation. Longer-term estimated incremental costs and quality-adjusted life-years were lower and net monetary benefit marginally favoured conservative oxygenation but with wide uncertainty [incremental costs −£879 (95% confidence interval −9036 to 7278); quality-adjusted life-years 0.001 (−0.010 to 0.011); net monetary benefit £894 (95% confidence interval −7290 to 9078)]. Limitations: Exclusion of two large paediatric intensive care unit populations, due to a lack of equipoise and the number of participants excluded because of not being able to obtain deferred consent. Future work: Future work should focus on identification of the mechanisms underlying the observed benefit; trials of intermediate or lower peripheral oxygen saturation values in individuals at higher risk; and identification of individualised treatment effects in relation to oxygen therapy. Conclusions: A conservative oxygenation target resulted in a greater probability of a better outcome in terms of duration of organ support at 30 days or death. Longer-term survival and health-related quality of life were consistent with the primary outcome. While conservative oxygenation is likely to reduce costs in the short term, longer-term cost-effectiveness was surrounded with wide uncertainty. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR127547.

OBJECTIVES: A conservative oxygenation strategy, targeting peripheral oxygen saturations (Spo ₂) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Spo ₂ greater than 94% in our recent Oxy-PICU trial. Spo ₂ monitors may overestimate arterial oxygen saturation (Sao ₂) in patients with higher levels of skin pigmentation compared with those with less skin pigmentation. We investigated if ethnicity was associated with changes in distributions of Spo ₂ and Fio ₂ and outcome. DESIGN: Post-hoc analysis of a pragmatic, open-label, multicenter randomized controlled trial. SETTING: Fifteen PICUs across the United Kingdom and Scotland. PATIENTS: Children aged 38 weeks corrected gestational age to 15 years accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. METHODS: Hierarchical regression models for Spo ₂ and Fio ₂, and ordinal models for the primary trial outcome of a composite of the duration of organ support at 30 days and death, were used to examine the effects of ethnicity, accounting for baseline Spo ₂, Fio ₂, and mean airway pressure and trial allocation. MEASUREMENTS AND MAIN RESULTS: Ethnicity data were available for 1577 of 1986 eligible children, 1408 (89.3%) of which were White, Asian, or Black. Spo ₂ and Fio ₂ distributions did not vary according to Black or Asian ethnicity compared with White children. The trial primary outcome measure also did not vary significantly with ethnicity. The point estimate for the treatment effect of conservative oxygenation in Black children was 0.64 (95% CI, 0.33–1.25) compared with 0.84 (0.68–1.04) in the overall trial population. CONCLUSIONS: These data do not suggest that the association between improved outcomes and conservative oxygenation strategy in mechanically ventilated children in PICU is modified by ethnicity.

Background and aims: The majority of smokers accessing the current best treatments continue to smoke. We aimed to test if e‐cigarettes (EC) compared with nicotine replacement treatment (NRT) can help such smokers to reduce smoking.Design: Randomized controlled trial of EC (n = 68) versus NRT (n = 67) with 6‐month follow‐up.Setting: Stop smoking service in London, UK.Participants: A total of 135 smokers (median age = 40 years, 51% male) previously unable to stop smoking with conventional treatments.Interventions: Participants received either NRT of their choice (8‐week supply) or an EC starter pack and instructions to purchase further e‐liquids of strength and flavours of their choice themselves. Products were accompanied by minimal behavioural support.Measurements: Participants who reported that they stopped smoking or reduced their daily cigarette consumption by at least 50% at 6‐month follow‐up were invited to provide a carbon monoxide (CO) reading. The primary outcome was biochemically validated reduction in smoke intake of at least 50% at 6 months and the main secondary outcome was sustained validated abstinence at 6 months. Drop‐outs were included as ‘non‐reducers’.Findings: Validated smoking reduction (including cessation) was achieved by 26.5 versus 6.0% of participants in the EC and NRT study arms, respectively [relative risk (RR) = 4.4, P = 0.005, 95% confidence interval (CI) = 1.6–12.4]. Sustained validated abstinence rates at 6 months were 19.1 versus 3.0% (RR = 6.4, P = 0.01, 95% CI = 1.5–27.3). Product use was high and equal in both study arms initially, but at 6 months allocated product use was 47% in the EC arm versus 10% in the NRT arm (χ²₍₁₎ = 22.0, P < 0.001), respectively. Adverse events were minor and infrequent.Conclusions: In smokers unable to quit using conventional methods, e‐cigarettes were more effective than nicotine replacement therapy in facilitating validated long‐term smoking reduction and smoking cessation when limited other support was provided.