Use of selective gut decontamination in critically ill children: PICnIC a pilot RCT and mixed-methods study.

Background: Healthcare-associated infections are a major cause of morbidity and mortality in critically ill children. In adults, data suggest the use of selective decontamination of the digestive tract may reduce the incidence of healthcare-associated infections. Selective decontamination of the digestive tract has not been evaluated in the paediatric intensive care unit population. Objectives: To determine the feasibility of conducting a multicentre, cluster-randomised controlled trial in critically ill children comparing selective decontamination of the digestive tract with standard infection control. Design: Parallel-group pilot cluster-randomised controlled trial with an integrated mixed-methods study. Setting: Six paediatric intensive care units in England. Participants: Children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 hours were eligible for the PICnIC pilot cluster-randomised controlled trial. During the ecology periods, all children admitted to the paediatric intensive care units were eligible. Parents/legal guardians of recruited patients and healthcare professionals working in paediatric intensive care units were eligible for inclusion in the mixed-methods study. Interventions: The interventions in the PICnIC pilot cluster-randomised controlled trial included administration of selective decontamination of the digestive tract as oro-pharyngeal paste and as a suspension given by enteric tube during the period of mechanical ventilation. Main outcome measures: The decision as to whether a definitive cluster-randomised controlled trial is feasible is based on multiple outcomes, including (but not limited to): (1) willingness and ability to recruit eligible patients; (2) adherence to the selective decontamination of the digestive tract intervention; (3) acceptability of the definitive cluster-randomised controlled trial; (4) estimation of recruitment rate; and (5) understanding of potential clinical and ecological outcome measures. Results: A total of 368 children (85% of all those who were eligible) were enrolled in the PICnIC pilot cluster-randomised controlled trial across six paediatric intensive care units: 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering selective decontamination of the digestive tract, the majority (98%) of children received at least one dose of selective decontamination of the digestive tract, and of these, 68% commenced within the first 6 hours. Consent for the collection of additional swabs was low (44%), though data completeness for potential outcomes, including microbiology data from routine clinical swab testing, was excellent. Recruited children were representative of the wider paediatric intensive care unit population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cluster-randomised controlled trial of 3 children/site/week, based on data from all UK paediatric intensive care units. The proposed trial, including consent and selective decontamination of the digestive tract, was acceptable to parents and staff with adaptations, including training to improve consent and communication, and adaptations to the administration protocol for the paste and ecology monitoring. Clinical outcomes that were considered important included duration of organ failure and hospital stay, healthcare-acquired infections and survival. Limitations: The delivery of the pilot cluster-randomised controlled trial was disrupted by the COVID-19 pandemic, which led to slow set-up of sites, and a lack of face-to face training. Conclusions: PICnIC's findings indicate that a definitive cluster-randomised controlled trial in selective decontamination of the digestive tract in paediatric intensive care units is feasible with the inclusion modifications, which would need to be included in a definitive cluster-randomised controlled trial to ensure that the efficiency of trial processes is maximised. Future work: A definitive trial that incorporates the protocol adaptations and outcomes arising from this study is feasible and should be conducted. Trial registration: This trial is registered as ISRCTN40310490. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/152/01) and is published in full in Health Technology Assessment; Vol. 28, No. 8. See the NIHR Funding and Awards website for further award information.

Each year, around 20,000 critically ill children are admitted to paediatric intensive care units in the UK. These children are at a higher risk of healthcare-associated infections, one of the main sources of which is the large number of bacteria in the digestive tract. Spread of bacteria from the digestive tract into other organs, such as the lung (causing ventilator-associated pneumonia) or bloodstream (causing sepsis), can be life-threatening. The risk is highest in those children whose illness is so severe that they require prolonged mechanical ventilation. Stopping the growth of bacteria in the digestive tract (called selective decontamination of the digestive tract) has been shown in adults to reduce the number of hospital-acquired infections. However, there have been no trials in children. We wanted to assess how practical and acceptable such a trial would be comparing standard infection control to selective decontamination of the digestive tract-enhanced infection control and monitoring how each intervention affected antimicrobial resistance. We undertook a pilot study to examine whether clinicians could identify eligible children, enrol them in the study and follow study procedures during the course of paediatric intensive care unit admission. Alongside this, we interviewed parents and clinicians to get their views on the proposed trial. Six hospitals recruited 559 patients over a period of roughly 7 months. Hospitals were randomly allocated to continue with the standard infection control procedure or to give selective decontamination of the digestive tract. Overall, recruitment was higher than expected. Alongside this, we examined the views of patients, caregivers and healthcare professionals to assess their views on whether a trial should be carried out to see if selective decontamination of the digestive tract should become part of the infection control regime for children most at risk of hospital-acquired infection in the paediatric intensive care unit. Overall results suggest that a larger PICnIC trial incorporating patient stakeholder and clinical staff feedback on design and outcomes is feasible and that it is appropriate to conduct a trial into the effectiveness of selective decontamination of the digestive tract administration to minimise hospital-acquired infections.

Implementing early rehabilitation and mobilisation for children in UK paediatric intensive care units: the PERMIT feasibility study.

Background: Early rehabilitation and mobilisation encompass patient-tailored interventions, delivered within intensive care, but there are few studies in children and young people within paediatric intensive care units. Objectives: To explore how healthcare professionals currently practise early rehabilitation and mobilisation using qualitative and quantitative approaches; co-design the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual of early rehabilitation and mobilisation interventions, with primary and secondary patient-centred outcomes; explore feasibility and acceptability of implementing the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual within three paediatric intensive care units. Design: Mixed-methods feasibility with five interlinked studies (scoping review, survey, observational study, codesign workshops, feasibility study) in three phases. Setting: United Kingdom paediatric intensive care units. Participants: Children and young people aged 0-16 years remaining within paediatric intensive care on day 3, their parents/guardians and healthcare professionals. Interventions: In Phase 3, unit-wide implementation of manualised early rehabilitation and mobilisation. Main outcome measures: Phase 1 observational study: prevalence of any early rehabilitation and mobilisation on day 3. Phase 3 feasibility study: acceptability of early rehabilitation and mobilisation intervention; adverse events; acceptability of study design; acceptability of outcome measures. Data sources: Searched Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, PEDro, Open grey and Cochrane CENTRAL databases. Review methods: Narrative synthesis. Results: In the scoping review we identified 36 full-text reports evaluating rehabilitation initiated within 7 days of paediatric intensive care unit admission, outlining non-mobility and mobility early rehabilitation and mobilisation interventions from 24 to 72 hours and delivered twice daily. With the survey, 124/191 (65%) responded from 26/29 (90%) United Kingdom paediatric intensive care units; the majority considered early rehabilitation and mobilisation a priority. The observational study followed 169 patients from 15 units; prevalence of any early rehabilitation and mobilisation on day 3 was 95.3%. We then developed a manualised early rehabilitation and mobilisation intervention informed by current evidence, experience and theory. All three sites implemented the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual successfully, recruited to target (30 patients recruited) and followed up the patients until day 30 or discharge; 21/30 parents consented to complete additional outcome measures. Limitations: The findings represent the views of National Health Service staff but may not be generalisable. We were unable to conduct workshops and interviews with children, young people and parents to support the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual development due to pandemic restrictions. Conclusions: A randomised controlled trial is recommended to assess the effectiveness of the manualised early rehabilitation and mobilisation intervention. Future work: A definitive cluster randomised trial of early rehabilitation and mobilisation in paediatric intensive care requires selection of outcome measure and health economic evaluation. Study registration: The study is registered as PROSPERO CRD42019151050. The Phase 1 observational study is registered Clinicaltrials.gov NCT04110938 (Phase 1) (registered 1 October 2019) and the Phase 3 feasibility study is registered NCT04909762 (Phase 3) (registered 2 June 2021). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/21/06) and is published in full in Health Technology Assessment; Vol. 27, No. 27. See the NIHR Funding and Awards website for further award information.

Early rehabilitation and mobilisation, within the first week of intensive care admission, can improve the speed of recovery from illness or injury in adults. However, there is a lack of evidence about whether critically unwell children benefit from early rehabilitation and mobilisation. We aimed to identify which patients may benefit from early rehabilitation and mobilisation. Also, to develop and test a manual of early rehabilitation and mobilisation using the best evidence and expertise ­ called the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual. Then evaluate whether the manual could be implemented safely in paediatric intensive care units and was acceptable to staff and families. We undertook in respect of early rehabilitation and mobilisation: review of existing research; national survey of practice (124 staff); gathered information about current conduct (15 paediatric intensive care units, 169 patients); spoke to experts (18 people); developed the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual to guide paediatric intensive care unit staff; Tested the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual in three paediatric intensive care units with 30 patients; gathered feedback from healthcare professionals via weekly 'debriefs' (47), interviews (13) and surveys (118), and from parents via parent-completed questionnaires (21) and interviews (14). Despite being regarded as important, currently early rehabilitation and mobilisation practice is inconsistent, not considered 'early' enough and often focuses on low-risk activities conducted on the bed. Introducing the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual as part of a trial was acceptable and feasible and helps standardise delivery to unwell children. Measuring child and parent reported outcomes was acceptable but follow-up at 30 days was incomplete. A larger trial of early rehabilitation and mobilisation, involving more paediatric intensive care units, is feasible and required to demonstrate benefit to children.

A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era.

Background: In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. Methods: An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. Results: Seventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. Conclusions: Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. Trial registration: Clinicaltrials.gov, NCT04233268. Registered on 18 January 2020. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-023-00008-z.

Relationship between inflammation and metabolic regulation of energy expenditure by GLP-1 in critically ill children.

BACKGROUND & AIMS: Critical illness is associated with derangement in the metabolic and inflammatory response. Previous investigators have highlighted the cross-link between feeding, inflammation and gut homeostasis. Glucagon like peptide-1 (GLP-1) is a gut derived hormone that plays an important role in the modulation of energy metabolism through appetite regulation and promotion of gastric motility. Growing evidence suggests that GLP-1 might influence energy expenditure. The aim of this study was to assess the relationship between inflammatory activation and metabolic regulation of energy expenditure by assessing cytokine release, levels of GLP-1 and energy expenditure in a cohort of critically ill children. METHOD: This is a prospective study conducted in critically ill children. A blood sample was collected from each child during the first few days of critical illness, for the analysis of serum inflammatory cytokines (TNF-α, IL-10, IL-6 and IL-1ß) and GLP-1 in 42 children. Indirect calorimetry (IC) measurements were performed concurrently in a subset of 21 children. The metabolic index was determined using the ratio of Measured Resting Energy Expenditure (MREE)/Predicted Resting Energy Expenditure (PREE) based on the Schofield equation. Correlation analysis was performed, followed by a stepwise linear regression analysis to assess factors affecting GLP-1 and the metabolic index. RESULTS: A total of 42 children (0-14 years) were included in this study. The regression analysis indicated that CRP, TNF-α, IL-6 and IL-1ß statistically influenced GLP-1 concentrations (p < 0.01). Where IC measurements were performed (N = 21), GLP-1 showed a statistically significant association with the metabolic index (p < 0.01). No evidence of statistical association was recorded between the inflammatory mediators and the metabolic index. Overall the results showed that circulating GLP-1 was increased in response to inflammatory stimuli in critically ill children. GLP-1 contributed to the changes observed in MREE induced by critical illness in our cohort. CONCLUSION: Energy expenditure is extremely variable in critically ill children, our study suggests that changes in GLP-1 might contribute to a significant amount of this variation. If confirmed in larger studies, GLP-1 could be used as a correction factor for REE predictive equations in critically ill children.

Routine gastric residual volume measurement to guide enteral feeding in mechanically ventilated infants and children: the GASTRIC feasibility study.

BACKGROUND: The routine measurement of gastric residual volume to guide the initiation and delivery of enteral feeding is widespread in paediatric intensive care and neonatal units, but has little underlying evidence to support it. OBJECTIVE: To answer the question: is a trial of no gastric residual volume measurement feasible in UK paediatric intensive care units and neonatal units? DESIGN: A mixed-methods study involving five linked work packages in two parallel arms: neonatal units and paediatric intensive care units. Work package 1: a survey of units to establish current UK practice. Work package 2: qualitative interviews with health-care professionals and caregivers of children admitted to either setting. Work package 3: a modified two-round e-Delphi survey to investigate health-care professionals' opinions on trial design issues and to obtain consensus on outcomes. Work package 4: examination of national databases to determine the potential eligible populations. Work package 5: two consensus meetings of health-care professionals and parents to review the data and agree consensus on outcomes that had not reached consensus in the e-Delphi study. PARTICIPANTS AND SETTING: Parents of children with experience of ventilation and tube feeding in both neonatal units and paediatric intensive care units, and health-care professionals working in neonatal units and paediatric intensive care units. RESULTS: Baseline surveys showed that the practice of gastric residual volume measurement was very common (96% in paediatric intensive care units and 65% in neonatal units). Ninety per cent of parents from both neonatal units and paediatric intensive care units supported a future trial, while highlighting concerns around possible delays in detecting complications. Health-care professionals also indicated that a trial was feasible, with 84% of staff willing to participate in a trial. Concerns expressed by junior nurses about the intervention arm of not measuring gastric residual volumes were addressed by developing a simple flow chart and education package. The trial design survey and e-Delphi study gained consensus on 12 paediatric intensive care unit and nine neonatal unit outcome measures, and identified acceptable inclusion and exclusion criteria. Given the differences in physiology, disease processes, environments, staffing and outcomes of interest, two different trials are required in the two settings. Database analyses subsequently showed that trials were feasible in both settings in terms of patient numbers. Of 16,222 children who met the inclusion criteria in paediatric intensive care units, 12,629 stayed for > 3 days. In neonatal units, 15,375 neonates < 32 weeks of age met the inclusion criteria. Finally, the two consensus meetings demonstrated 'buy-in' from the wider UK neonatal communities and paediatric intensive care units, and enabled us to discuss and vote on the outcomes that did not achieve consensus in the e-Delphi study. CONCLUSIONS AND FUTURE WORK: Two separate UK trials (one in neonatal units and one in paediatric intensive care units) are feasible to conduct, but they cannot be combined as a result of differences in outcome measures and treatment protocols, reflecting the distinctness of the two specialties. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42110505. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 23. See the NIHR Journals Library website for further project information.

Nurses looking after babies and children on intensive care units in the UK usually pass a tube and aspirate whatever food or fluid is in the baby's stomach before they give a feed. The idea is to ensure that the stomach is not overdistended with food and prevent the baby vomiting or, worse, aspirating food into the lungs. However, there is little justification for this practice. It is rarely done in many other countries. It may not be pleasant for the child and perhaps is unnecessary. Some experts have suggested that the policy should be evaluated in a randomised controlled trial. This would mean allocating a large number of children at random to either have the stomach aspirated before feeds, or not. Such a trial would be a major undertaking and we are unsure if parents or staff would be willing to allow children to participate. The aim of this study was to see if it is possible to conduct such a large trial in the UK. Two surveys (of 119 units) showed us that regularly measuring the stomach contents when starting and increasing feeds is common practice for both newborn and older children in UK intensive care units. However, in some countries, such as France, this practice is rarely done. We asked 31 parents and 51 health-care professionals about a future study. Overall, parents were supportive of a trial if it was explained to them well by a knowledgeable and caring professional, and if they were approached at the right time. Some concerns were expressed about not picking up complications early if gastric residual volume was not measured. Health-care professionals were also mainly positive about a future trial, but mentioned similar concerns about not picking up complications early and the difficulty of changing a long-standing routine practice. Parents suggested study outcomes that were important to them. These, along with other outcomes, were voted on in a further survey of 106 professionals and at face-to-face meetings involving 41 participants. Overall, our findings suggest that a trial is feasible to perform and acceptable to parents. However, because of differences in both treatments and important outcomes between children's intensive care units and newborn baby intensive care units, two trials would be needed, one in each type of intensive care unit. These two trials will test whether or not the benefits of not measuring gastric residual volume (e.g. improved calorie intake) outweigh the potential harms (e.g. delayed diagnosis of complications).

Challenge of predicting resting energy expenditure in children undergoing surgery for congenital heart disease.

OBJECTIVES: To determine pre- and postoperative predictors of energy expenditure in children with congenital heart disease requiring open heart surgery; and to compare measured resting energy expenditure with current predictive equations. DESIGN: Prospective resting energy expenditure data were collected, using indirect calorimetry, for ventilated children admitted consecutively to the pediatric intensive care unit after surgery for congenital heart disease. A 30-min steady-state measurement was performed in suitable patients. Resting energy expenditure was compared to pre- and postoperative clinical variables, and to predicted energy expenditure, using currently used predictive equations. SETTING: Pediatric intensive care unit at the Royal Brompton Hospital, London. PATIENTS: Children ventilated in the pediatric intensive care unit post surgery for congenital heart disease. INTERVENTIONS: Measurement of energy expenditure by indirect calorimetry. MEASUREMENTS AND MAIN RESULTS: Twenty-one mechanically ventilated children (n = 17 boys, 4 girls) were enrolled in the study. Mean +/- sd measured resting energy expenditure was 67.8 +/- 15.4 kcal/kg/day. Most children had inadequate delivery of nutrients compared with actual requirements. Cardiopulmonary bypass had a significant influence on energy expenditure after surgery; in patients who underwent cardiopulmonary bypass during surgery, mean resting energy expenditure was 73.6 +/- 14.45 kcal/kg/day vs. 58.3 +/- 10.29 kcal/kg/day in patients undergoing nonbypass surgery. Children who were malnourished preoperatively had greater resting energy expenditure postoperatively. There was also a significant difference between measured energy expenditure and the Schofield (p = .006), World Health Organization (p = .002), and pediatric intensive care unit-specific formula (p < .0001). However, energy expenditure or a relative energy deficit in the early postoperative period was not associated with severity or duration of organ dysfunction. CONCLUSIONS: Poor nutritional status preoperatively and cardiopulmonary bypass were associated with a greater energy expenditure post cardiac surgery. None of the current predictive equations predicted energy requirements within acceptable clinical accuracy.