National survey of feasibility of NIV trials for management of children with bronchiolitis

1 RosalaHallasA, etal. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/bmjpo-2020-000780 Open access National survey of feasibility of NIV trials for management of children with bronchiolitis Anna RosalaHallas ,1 Ashley P Jones ,1 Emma Bedson,1 Vanessa Compton,2 Ricardo M Fernandes,3,4 David Lacy,5 Mark D Lyttle,6,7 Matthew Peak,8 Kent Thorburn,2 Clare van Miert,2,9 Kerry Woolfall,10 Paul S McNamara11 To cite: RosalaHallasA, JonesAP, BedsonE, etal. National survey of feasibility of NIV trials for management of children with bronchiolitis. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/ bmjpo-2020-000780 Received 26 June 2020 Revised 7 August 2020 Accepted 25 August 2020 For numbered affiliations see end of article. Correspondence to Dr Paul S McNamara; mcnamp@ liverpool. ac. uk Original research © Author(s) (or their employer(s)) 2020. Reuse permitted under CC BYNC. No commercial reuse. See rights and permissions. Published by BMJ. ABSTRACT Background Bronchiolitis is a major cause of admission to hospital in children. Noninvasive ventilation (NIV) support with continuous positive airway pressure (CPAP) or highflow nasal cannula (HFNC) oxygen is routinely used for infants in the UK with bronchiolitis. Objective To establish UK paediatric practice regarding management of bronchiolitis, and to explore issues pertinent to the design of a potential future randomised controlled trial of NIV. Design Screening logs were completed in hospitals in England capturing information on paediatric bronchiolitis admissions. An online national survey of clinical practice was disseminated to healthcare professionals (HCPs) across the UK to ascertain current management strategies. Results Screening logs captured data on 393 infants from 8 hospitals. Reasons for admission were most commonly respiratory distress and/or poor fluid intake. Oxygen was administered for 54% of admissions. Respiratory (CPAP and HFNC) and nonrespiratory support administered varied considerably. The national survey was completed by 111 HCPs from 76 hospitals. Data were obtained on criteria used to commence and wean NIV, responsibilities for altering NIV settings, minimum training requirements for staff managing a child on NIV, and numbers of trained staff. Most centres were interested in and capable of running a trial of NIV, even out of normal office hours. Conclusions Respiratory and nonrespiratory management of bronchiolitis in UK centres varies widely. A trial of HFNC oxygen therapy in this group of patients is feasible and HCPs would be willing to randomise patients into such a trial. Future work should focus on defining trial eligibility criteria. INTRODUCTION Bronchiolitis is a major cause of admission to hospital in children.1 2 Between 2004 and 2012, 8172 children under the age of 1 year were admitted to a paediatric intensive care unit (PICU) for bronchiolitis in England.3 From 2004 to 2011, the overall average PICU admission rate increased by 1.8% each year.3 Bronchiolitis management is centred on oxygen therapy for hypoxia, respiratory support and good hydration. Early use of noninvasive ventilation (NIV), such as continuous positive airway pressure (CPAP) or heated humidified highflow nasal (HFNC) oxygen (O2), may have an impact on outcome by avoiding disease progression.4 There has been an increase in the use of HFNC in routine clinical practice for moderatetosevere bronchiolitis; however, until recently, there has been little evidence to guide practice, and there have been no studies using NHS patients from the UK.5 6 Recently, a number of reports have raised concerns regarding its cost effectiveness in bronchiolitis.7 The objectives of this study were to assess current UK practice regarding bronchiolitis management in terms of the type of NIV methods used and the criteria for commencing and weaning NIV. We also wished to explore issues pertinent to the design of a potential future randomised controlled trial (RCT) of NIV. This study formed part of a larger research project (NonInvasive Ventilation What is known about the subject? ►Bronchiolitis is one of the the most common causes of hospitalisation in infancy. ►Noninvasive ventilation and specifically highflow nasal cannula oxygen therapy is increasingly used for children with bronchiolitis based on limited evidence in the UK. ►There is widespread support among paediatricians in the UK for a trial of noninvasive ventilation to guide UK practice. What this study adds? ►Respiratory and nonrespiratory management of bronchiolitis in UK centres varies widely. ►A trial of highflow nasal cannula oxygen therapy is feasible and healthcare professionals would be willing to randomise patients into such a trial. on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from 2RosalaHallasA, etal. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/bmjpo-2020-000780 Open access for the Management of Children with Bronchiolitis: a feasibility study (NOVEMBR)).8 METHODS A pointprevalence study, using paper screening logs of paediatric hospital admissions with bronchiolitis, was prospectively completed, by research nurses from district general hospitals and paediatric tertiary centres hospitals across England. The logs gave guidelines for completion and captured: patient age, referral route, demographic and clinical risk factors, reasons for admission, treatment interventions during admission, method of O2 delivery and amount of O2 (if any), and length of hospital stay. In total, 14 hospitals were approached for participation of which eight responded (five district general hospitals and three paediatric hospitals; see online supplemental list 1 for a list of the hospitals). The logs were circulated in two waves: the first wave included five hospitals and ran from 12 December 2016 to 12 January 2017; the second wave included three different hospitals from 11 December 2017 to 13 January 2018. The same log was used for all hospitals; repeat sampling was not used. Data on all patients admitted with a diagnosis of bronchiolitis during these time periods to these hospitals were captured. In addition, an online national survey (online supplemental material) was developed by the study management group to explore current practices of HCPs when managing bronchiolitis. The survey was piloted among clinical members of the Study Management Group, which comprised PICU, respiratory and general paediatricians, paediatric nurses and research nurses. Amendments made from the piloting process were improvements to the clarity and understanding of the survey by changes to some of the language. The survey was disseminated to lead paediatricians at all paediatric centres in the UK through the National Institute for Health Research Clinical Research Network (CRN) Coordinating Centre to Specialty Cluster Office for Children and Local CRNs, and through the General and Adolescent Paediatric Research Collaborative UK and Ireland. The lead paediatricians were asked to complete the survey themselves or to pass it on to whoever they considered most appropriate. It was conducted online between 29 September 2017 and 31 January 2018. Respondents were asked to report their job title and give information about their hospital including: the number of estimated paediatric bronchiolitis admissions, type of NIV interventions used and who administers them, criteria for initiating and weaning CPAP and HFNC, availability of local bronchiolitis care pathways and lastly, questions to determine the acceptability to HCPs of running a clinical trial. Completion of the survey was deemed consent to participate. Data from both the screening logs and the online national survey were summarised using descriptive statistics. Where questions were missed or responses ‘Not known’, percentages were derived using denominators for those who gave an answer only. Advice from the HRA was sought and it was confirmed that ethical approval was not required for the online survey. Approval was not required for the screening exercise as only anonymous data were collected. Patient and Public Involvement (PPI) was not included forthis component of the NOVEMBR study since the aim was to ascertain currentpractice amongst HCPs. RESULTS Screening logs Table 1 gives a summary of the screening data. Three hundred and ninetythree patients were screened at eight hospitals across England (online supplemental list 1). Data by hospital are presented in online supplemental table 1. The greatest proportion (139/357, 39%) were admitted in the afternoon and early evening (14:00–20:00). Median age at admission was 14 weeks (IQR: 8–29) and median length of hospital stay was 2 days (IQR: 1–3). Most referrals were via emergency departments (246/391, 63%) or from general practitioners (99/391, 25%). It was possible for multiple reasons for admission to be selected for each patient; among the most frequent, over half (203/392, 52%) reported difficulty with breast feeding/inadequate oral fluid intake, 36% (142/392) other respiratory problems, including cough and increased work of breathing, 31% (121/392) severe respiratory distress and 27% (106/392) of children looked seriously unwell to a HCP. Commonly reported risk factors for hospital admission included age less than 3 months (165/357, 46%) and/ or prematurity (89/357, 25%); 34% (120/357) reported no risk factors. Nonrespiratory interventions included: nasogastric fluids (157/354, 44%), antibiotics (87/354, 25%), nebulised treatments (52/354, 15%) and intravenous fluids (37/354, 10%); 38% (134/354) reported no treatment intervention. There was considerable variation across hospitals: nasogastric fluids use ranged from 17% to 77% of infants, antibiotics from 9% to 67%, nebulisers from 7% to 55% and intravenous fluids from 1% to 37% (figure 1). Oxygen was delivered to 191 (54%) patients. Multiple methods for O2 delivery could be selected; methods reported were lowflow nasal cannula (103/191, 54%), rebreathe mask (42/191, 22%), head box with humidified O2 (25/191, 13%), HFNC (52/191, 27%), CPAP (18/191, 9%) and intubation and ventilation (21/191, 11%). National online survey of current practice The survey was accessed by 123 individuals. Twelve (9%) completed demographic details only and were excluded from the summaries; the remaining 111 (91%) responders were from 76 hospitals (online supplemental list 2). The majority (83/111, 75%) of respondents were from district general hospitals; 25% (28/111) were from paediatric tertiary centres. According to the Royal College of Paediatrics and Child Health workforce document published in 2019, there are 189 paediatric centres with inpatient facilities in the UK of which 35 are considered specialist on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from 3 RosalaHallasA, etal. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/bmjpo-2020-000780 Open access (tertiary) centres.9 Respondents were either consultants (92/109, 84%) or nurses (12/109, 11%, table 2). Almost half (47%, 38/81) of respondents stated that the estimated annual number of paediatric bronchiolitis admissions to their hospital with a length of stay of at least 1 day, was between 101 and 200, and 30% (24/81) estimated between 51 and 100. The majority (71/84, 85%) of respondents stated local bronchiolitis care pathways and/or guidance were available to them; 86% (75/87) reported the criteria for starting O2 was SpO2 <92%. Six respondents (6/88, 7%), from separate hospitals, reported the ability to send home children with bronchiolitis on O2. Table 1 Screening data N (%) Patient age (weeks) N 378 Mean (SD) 20.0 (15.9) Median (IQR) 14.2 (7.5–29.1) Min, Max 1.3–82.4 Missing 15 Length of stay in hospital (days) N 390 Mean (SD) 2.7 (3.0) Median (IQR) 2 (1.3) Min, max 0–24 Missing 3 Time of presentation N 357 02:00–08:00 36 (10%) 08:00–14:00 81 (23%) 14:00–20:00 139 (39%) 20:00–02:00 101 (28%) Missing 36 Referral route N 391 Accident and emergency 246 (63%) District general hospital 16 (4%) General practitioner 99 (25%) Open access 17 (4%) Other hospital 10 (3%) Readmission 1 (0.3%) Walkin 2 (0.5%) Not known 2 Risk factors* N 357 Baby born prematurely 89 (25%) Congenital heart defect 7 (2%) Neuromuscular disease 1 (<1%) Immunodeficiency disorders 2 (1%) Chronic lung disease 8 (2%) Young age (≤3 months) 165 (46%) Other 24 (7%) No risk factors 120 (34%) Not known 1 Missing 35 Reason for admission* N 392 Apnoea (reported or observed) 21 (5%) Child looks seriously unwell to a HCP 106 (27%) Continued N (%) Severe respiratory distress 121 (31%) Central cyanosis 3 (1%) Persistent O2 saturation <92% when breathing air 30 (8%) Difficulty with breast feeding/ inadequate oral fluid intake 203 (52%) Social circumstances 2 (1%) Other respiratory 142 (36%) Other 50 (13%) Missing 1 Method* of O2 delivery N 191 Nasal Cannula 103 (54%) Headbox with humidified O225 (13%) Heated humidified highflow nasal O252 (27%) Rebreathe mask 42 (22%) CPAP 18 (9%) Intubation and ventilation 21 (11%) Other 13 (7%) No O2 used 162 Not known 3 Missing 37 *Multiple responses could be selected. CPAP, continuous positive airway pressure; HCP, healthcare professional. Table 1 Continued Figure 1 Screening responses—treatment interventions across hospitals. on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from 4RosalaHallasA, etal. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/bmjpo-2020-000780 Open access CPAP/HFNC More respondents reported being able to deliver O2 on paediatric wards by HFNC (73/86, 85%) than CPAP (49/86, 57%); 55% reported the ability to deliver O2 using both treatment modalities. On High Dependency Units (HDU), the ability to deliver O2 using either was similar (HFNC, 70/73, 96%; CPAP, 64/73, 88%). The modal estimate of infants with bronchiolitis that did not require O2 on admission reported by respondents was 11%–20%, whereas the estimate of infants that did require O2 was 61%–70%. Although the modal estimate of infants treated with CPAP or HFNC was similar (0%–10%), the variation was more marked for HFNC, with some respondents estimating that up to 80% of patients requiring NIV in their centres would be treated with HFNC, compared with a maximum of 40% estimated to be treated with CPAP (online supplemental table 5). Apnoea, type 2 respiratory failure, exhaustion and the child not improving on alternate therapies (mostly HFNC) were more commonly cited as criteria to start CPAP compared with HFNC (figure 2, online Table 2 Survey participant/hospital demographics Participant and hospital demographics Number of respondents (%) Job title/role N 109 Consultant 92 (84%) Nurse 12 (11%) Other 5 (5%) Missing 2 Number of children with bronchiolitis admitted to hospital (with ≥1 day length of stay) per year N 81 <50 5 (6%) 51–100 24 (30%) 101–200 38 (47%) 201–300 9 (11%) 301–400 2 (2%) >401 3 (4%) Not known 28 Missing 2 Local bronchiolitis care pathways and/or guidance available N 84 Yes 71 (85%) No 13 (15%) Not known 6 Missing 21 Criteria for starting O2 N 87 SpO2 <92% 75 (86%) Other 12 (14%) Not known 2 Missing 22 Do you send otherwise well children with bronchiolitis who are improving, home on O2? N 88 Yes 6 (7%) No 82 (93%) Not known 3 Missing 20 Methods to deliver O2: therapy on the general medical practice ward* N 86 Nasal cannula 84 (98%) Heated humidified highflow nasal O273 (85%) Rebreathe mask 50 (58%) Noninvasive CPAP 49 (57%) Headbox with humidified O229 (34%) Continued Participant and hospital demographics Number of respondents (%) Missing 25 Methods to deliver O2: therapy on the High Dependency Unit* N 73 Heated humidified highflow nasal O270 (96%) Noninvasive CPAP 64 (88%) Nasal cannula 56 (77%) Rebreathe mask 39 (53%) Headbox with humidified O219 (26%) Missing 38 *Multiple responses could be select. CPAP, continuous positive airway pressure. Table 2 Continued Figure 2 Survey responses—criteria for initiating continuous positive airway pressure (CPAP) compared to highflow nasal cannula (HFNC). on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from 5 RosalaHallasA, etal. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/bmjpo-2020-000780 Open access supplemental table 3); HFNC was started for increased work of breathing more often than CPAP. Correspondingly, resolved apnoea, and improved C02/respiratory acidosis were more commonly cited as criteria for weaning CPAP compared with HFNC. Responsibilities for altering CPAP/HFNC settings lay predominantly with the nursing staff, who were responsible in 40% (23/57) of cases on CPAP compared with 77% (46/60) of cases on HFNC. Minimum training requirements for staff to manage a child on CPAP/HFNC were similar for both methods and included: annual attendance of inhouse training packages with and without clinical competency assessments, attendance to ad hoc training sessions run by equipment manufacturers and high dependency courses. Acceptability of a trial Most respondents (34/41, 83%) reported that it would be possible to run a clinical trial evaluating NIV treatment approaches in bronchiolitis even outofhours at their hospitals (online supplemental table 4). Forty respondents suggested at least one barrier to undertaking such a trial. Barriers included: current medical/nursing staff workload (15/40, 38%), availability of equipment (7/40, 18%), lack of research nurse support (4/40, 10%) and lack of adequately trained staff to undertake a trial (3/40, 8%). Correspondingly, 47 respondents suggested at least one enabler to undertaking a trial: having adequate medical, nursing and research nurse support (24/47, 51%), good training and education about any trial (8/47, 17%) and importantly, having access to extra equipment (8/47, 17%). Sixty per cent (47/78) estimated that 1–5 HDU beds would be available in winter. Respondents at 72% of sites reported always having one or more GCP trained doctor on every shift. Similarly, respondents at 45% of sites reported that their site had one or more GCP trained nurse on every shift. DISCUSSION In this prospective observational study of bronchiolitis admissions, large numbers of children (particularly young infants approximately 3 months of age) were hospitalised with this condition but generally for only a few days. Many (46%) did not require oxygen during their admission, but in those who did, the method by which it was administered varied widely; this was particularly so for those requiring NIV. Despite publication of The National Institute for Health and Care Excellence (NICE) guidelines on bronchiolitis in 2015,3 there remains considerable variation in other aspects of management. This study provided the opportunity to compare survey responses from a large number of UK paediatric HCPs with screening log data on actual bronchiolitis admissions to secondary and tertiary centres. Survey responses overestimated the proportion of children requiring O2 on admission compared with screening log data, and although modal estimates of CPAP usage were broadly in line with actual usage, estimates of HFNC usage underestimated actual usage. In interpreting these results, it should be acknowledged that the screening log data were based on admissions to only eight paediatric centres, and that there was a wide range of estimates of percentages of children treated with O2 and with NIV (particularly HFNC). It may also be the case that the screening results differ between district general hospitals and paediatric tertiary centres; however, our sample size did not permit such a comparison. We compared reasons for starting and weaning NIV. Apnoea, type 2 respiratory failure, exhaustion and the child not improving on alternate therapies (mostly HFNC) were more commonly cited as criteria to start CPAP. Correspondingly, resolved apnoea, and improved C02/respiratory acidosis were more commonly cited as weaning criteria for CPAP than HFNC. The overall consistency of approach to starting and weaning NIV suggests the need for a consensusbased clinically pragmatic protocol for any future trial, and that agreeing criteria and a protocol to initiate and wean NIV across sites in a future trial is feasible. Furthermore, such criteria have already been adopted for a UKbased pragmatic trial in critically ill children on both stepping up and stepping down noninvasive respiratory support.10 Based on our findings, we would question whether it is currently feasible for a HFNC versus CPAP trial to be undertaken outside of PICUs and highdependency units in the UK. This is primarily for reasons of capacity/capability, with many centres unable to support the use of CPAP on general paediatric wards and also given the recent funding and start of the FIRSTABC (Firstline support for Assistance in Breathing in Children) trial which is examining the noninferiority of HFNC compared with CPAP.10 However, a trial to assess the clinical effectiveness of HFNC versus standard oxygen therapy (‘standard’ agreed a priori) is feasible and one which many general paediatricians would likely support. A key issue for any such trial would be eligibility criteria. NOVEMBR and recently published RCTs of NIV for bronchiolitis suggest that eligibility cannot be based solely on the need for oxygen.5 6 We have shown here that although over half children hospitalised with bronchiolitis are hypoxic on admission, most do not require O2 for long (under 24 hours), do not deteriorate that frequently, and do not have prolonged inpatient admissions. Even for those hypoxic children at high risk of severe bronchiolitis (ie, those less than 3 months of age or born prematurely), the median (IQR) length of stay in hospital was only 2 (1–3) days. Key eligibility criteria for any future trial will likely have to include both need for O2 and increased work of breathing, and take into account risk factors such as young age/prematurity. It is these infants for whom HFNC likely has the biggest potential to demonstrate clinical and cost effectiveness. A retrospective cohort study published in 2018 identified predictors of escalated care in bronchiolitis and used these to derive a risk score to outline higher risk patients; validation of such a score would be beneficial.11 on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from 6RosalaHallasA, etal. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/bmjpo-2020-000780 Open access The screening logs highlighted a large variation in the frequency with which various nonrespiratory interventions were used in children with bronchiolitis. Variation on this scale has previously been reported between countries, but not to our knowledge within the UK.12 When designing potentially large multicentre trials of NIV for children with bronchiolitis, an appreciation of this sort of variation in practice may be needed when planning patient recruitment per site and trial acceptability. There were two limitations of note, the first being that in the survey multiple responses from the same hospital could have inflated the proportions for certain responses. To check the validity of our results, we looked at the results with each hospital included only once for each response level (online supplemental tables 2-4) and found that the proportions were similar. The second limitation was that participants from the same hospital occasionally reported different answers, which is likely due to different perspectives depending on the job roles of the respondents; however, sample sizes prevented us from exploring differences between HCP subgroups (ie, nurses from general paediatric wards and those from HDU). We have established that there is a wide variety of practice across the UK in the respiratory and nonrespiratory treatments given to infants with bronchiolitis. Our results also suggest that a trial of NIV is feasible and that HCPs would be willing to randomise patients into an NIV trial. Future work should now focus on defining the eligibility criteria for such a trial. Author affiliations 1Liverpool Clinical Trials Centre, Department of Biostatistics, University of Liverpool (a member of Liverpool Health Partners), Liverpool, UK 2Paediatric Intensive Care Unit, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK 3Instituto de Medicina Molecular, Clinical Pharmacology and Therapeutics, Faculty of Medicine, Universidade de Lisboa, Lisbon, Portugal 4Department of Paediatrics, Lisbon Academic Medical Centre, Hospital de Santa Maria, Lisbon, Portugal 5Department of Paediatrics, Wirral University Teaching Hospital NHS Foundation Trust, Wirral, UK 6Emergency Department, Bristol Royal Hospital for Children, Bristol, UK 7Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK 8Clinical Research Division, Alder Hey Children's NHS Foundation Trust, Liverpool, UK 9School of Nursing and Allied Health, Liverpool John Moores University, Liverpool, UK 10Institute of Population Health and Society, University of Liverpool, Liverpool, UK 11Institute of Child Health, University of Liverpool, Liverpool, UK Acknowledgements The authors would like to acknowledge the healthcare professionals who participated in the screening log and survey of national practice. They also would like to thank the funder, the NIHR Research for Patient Benefit Programme. Contributors CvM and PM conceived the study. CvM, PM, RF and KW designed the study. EB, MP, KT, VC and DL were members of the study management group. ARH analysed the data. AJ supervised data analysis. ARH, APJ and PM drafted the manuscript. All authors reviewed and provided comments on the manuscript. Funding This research was funded by the National Institute for Health Research (NIHR), Research for Patient Benefit (RfPB) Programme (Grant Reference Number PBPG-1014-35081). Disclaimer Views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Competing interests CvM was an invited speaker at a meeting sponsored by Fisher & Paykel. PM sits on an independent data monitoring and safety committee of an early phase trial of an antiviral treatment for bronchiolitis funded by Pulmocide and as an advisor for antiviral trials for bronchiolitis funded by Janssen and Alios. RF has served on independent data monitoring and safety committees of early phase trials in bronchiolitis funded by Ablynx and on a clinical endpoint committee for an RSV vaccine trial funded by Janssen. Patient consent for publication Not required. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available upon reasonable request. The datasets generated are available from the corresponding author on reasonable request. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peerreviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is noncommercial. See:http:// creativecommons. org/ licenses/ bync/ 4. 0/. ORCID iDs AnnaRosalaHallas http:// orcid. org/ 0000000180129995 Ashley PJones http:// orcid. org/ 000000015253730X REFERENCES 1 Florin TA, Plint AC, Zorc JJ. Viral bronchiolitis. Lancet 2017;389:211–24. 2 Reeves RM, Hardelid P, Gilbert R, etal. Estimating the burden of respiratory syncytial virus (RSV) on respiratory hospital admissions in children less than five years of age in England, 2007-2012. Influenza Other Respi Viruses 2017;11:122–9. 3 Green CA, Yeates D, Goldacre A, etal. Admission to hospital for bronchiolitis in England: trends over five decades, geographical variation and association with perinatal characteristics and subsequent asthma. Arch Dis Child 2016;101:140–6. 4 Nice bronchiolitis guideline, 2016. Available: https://www. nice. org. uk/ guidance/ ng9 [Accessed Feb 2020]. 5 Franklin D, Babl FE, Schlapbach LJ, etal. A randomized trial of highflow oxygen therapy in infants with bronchiolitis. 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Available: https:// fundingawards. nihr. ac. uk/ award/ 17/ 94/ 28 [Accessed Feb 2020]. 11 Freire G, Kuppermann N, Zemek R, etal. Predicting Escalated care in infants with bronchiolitis. Pediatrics 2018;142:e20174253. on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from 7 RosalaHallasA, etal. BMJ Paediatrics Open 2020;4:e000780. doi:10.1136/bmjpo-2020-000780 Open access 12 Schuh S, Babl FE, Dalziel SR, etal. Practice variation in acute bronchiolitis: a pediatric emergency research networks study. Pediatrics 2017;140:e20170842. on April 8, 2021 by guest. Protected by copyright.http://bmjpaedsopen.bmj.com/bmjpo: first published as 10.1136/bmjpo-2020-000780 on 27 October 2020. Downloaded from Non-Invasive Ventilation for the Management of Children with Bronchiolitis Survey - Supplementary Material List 1: Hospitals included in the screening exercise  Alder Hey Children’s NHS Foundation Trust  Brighton and Sussex University Hospitals NHS Trust  Cambridge University Hospitals NHS Foundation Trust  Countess of Chester NHS Foundation Trust  County Durham and Darlington NHS Foundation Trust  Derby Teaching Hospitals NHS Foundation Trust  Macclesfield Foundation Trust  Wolverhampton Foundation Trust BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A List 2: Hospitals included in the survey exercise  Airedale General Hospital  Altnagelvin Area Hospital  Birmingham Women and Children's Hospital  Blackpool Victoria Teaching Hospital  Bradford Teaching Hospital  Burton Hospitals NHS Foundation Trust  Calderdale Royal Hospital  Chesterfield Royal Hospital NHS Foundation Trust  Children's Hospital for Wales  Countess of Chester NHS Foundation Trust Hospital  Craigavon Area Hospital, Northern Ireland  Cumberland Infirmary, Carlisle  Daisy Hill Hospital, Newry  Darlington Memorial Hospital  Diana Princess of Wales Hospital, Grimsby  Dorset County Hospital  Durham and Darlington NHS Trust  East Cheshire NHS Trust  Gloucestershire Hospitals NHS Trust  Great North Children's Hospital Newcastle upon Tyne  Great Western Hospital, Swindon  Hampshire Hospitals NHS Trust  Heart of England NHS Foundation Trust  Hereford County Hospital  Hillingdon Hospital  James Cook University Hospital  King's Mill Hospital  Kingston Hospital NHS Foundation Trust  Leeds Children's Hospital  Leicester Royal Infirmary  Leighton Hospital, Crewe  Musgrove Park Hospital  Norfolk and Norwich University Hospital  North Devon District Hospital  North Middlesex Hospital  Northumbria Specialist Emergency Care Hospital  Nottingham Children's Hospital  Ormskirk District General Hospital  Oxford University Hospitals NHS Trust  Poole Hospital NHS Foundation Trust  Princess Alexandra Hospital NHS Trust  Queen Alexandra Hospital, Portsmouth  Raigmore Hospital - NHS Highland  Royal Aberdeen Children's Hospital  Royal Belfast Hospital for Sick Children  Royal Derby Hospital  Royal Devon and Exeter Hospital  Royal Free London NHS Foundation Trust  Royal Hospital for Sick Children, Edinburgh BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Individual respondents Hospitals (Participants from the same hospital may have given different answers) CPAP N (%) HFNC N (%) CPAP N (%) HFNC N (%) Clinical improvement/stability 21 (40%) 22 (39%) 16 (36%) 19 (37%) Improving Carbon dioxide, reducing respiratory acidosis 20 (38%) 15 (27%) 18 (40%) 10 (20%) Resolved apnoeas 7 (13%) 3 (5%) 7 (16%) 3 (6%) Tolerating feeds 2 (4%) 3 (5%) 2 (4%) 3 (6%) Other 7 (13%) 10 (18%) 6 (13%) 8 (16%) Missing 11 12 7 12 Who is responsible for altering CPAP/HFNC settings?* N Medical Staff 57 55 (96%) 60 53 (88%) 47 45 (96%) 53 47 (89%) Nursing Staff 23 (40%) 46 (77%) 22 (47%) 41 (77%) Respiratory Physiotherapist 1 (2%) 1 (2%) 1 (2%) 1 (2%) Not known 1 1 1 1 Missing 6 7 6 7 Minimum training requirement(s) for staff to manage a child on CPAP/HFNC* N Annual attendance of an in-house training package with clinical competency assessment 48 23 (48%) 51 19 (37%) 40 20 (50%) 44 17 (39%) Annual attendance of an in-house training package without clinical competency assessment 14 (29%) 16 (31%) 13 (33%) 14 (32%) Attendance on an ad hoc training session run by manufacturer 10 (21%) 22 (43%) 9 (23%) 20 (45%) High dependency course 10 (20%) 4 (8%) 10 (25%) 4 (9%) Other 14 (29%) 13 (25%) 13 (33%) 13 (30%) None 3 (6%) 1 (2%) 3 (8%) 1 (2%) Not known 12 12 11 12 Missing 4 5 4 5 *Multiple responses could be selected. BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Supplementary Table 4: Survey responses for acceptability for a trial Participant and hospital demographics Number of respondents (%) Number of hospitals (%) Number of HDU beds in winter 0 12 (15%) 12 (19%) 1-5 47 (60%) 37 (60%) 6-10 15 (19%) 14 (23%) 10+ 4 (5%) 4 (6%) Not known 9 9 Missing 24 23 Number of whole-time equivalent paediatric research nurses working at hospital 0 9 (19%) 9 (20%) >0 & <1 9 (19%) 8 (17%) ≥1 30 (63%) 29 (63%) Not known 18 14 Missing 45 38 Number of Good Clinical Practice trained ward nurses on an average shift 0 13 (57%) 12 (55%) >0 & <1 0 (0%) 0 (0%) ≥1 10 (43%) 10 (45%) Not known 39 32 Missing 49 38 Number of Good Clinical Practice trained doctors on an average shift 0 3 (11%) 3 (12%) >0 & <1 4 (15%) 4 (16%) ≥1 20 (74%) 18 (72%) Not known 36 33 Missing 48 40 Ability to run a clinical trial on how best to provide non-invasive ventilation in children with bronchiolitis out-of-hours1 Yes 34 (83%) 31 (84%) No 7 (17%) 7 (19%) Not known 29 26 Missing 41 34 1Monday - Friday 17:00 - 08:00 or weekends BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Supplementary Table 5: Estimated percentage of children1 admitted to hospital for bronchiolitis receiving the following treatments (excluding A&E short stay patients) Percentage of children Number (%) of respondents No O2 O2 CPAP Heat Intubation 0%-10% 20 (26%) 1 (1%) 47 (59%) 25 (31%) 74 (93%) >10%-20% 24 (31%) 2 (2%) 25 (32%) 15 (19%) 4 (5%) >20%-30% 21 (27%) 5 (6%) 5 (6%) 16 (20%) 2 (3%) >30%-40% 8 (10%) 3 (4%) 2 (3%) 9 (11%) 0 (0%) >40%-50% 4 (5%) 9 (11%) 0 (0%) 6 (8%) 0 (0%) >50%-60% 0 (0%) 9 (11%) 0 (0%) 5 (6%) 0 (0%) >60%-70% 0 (0%) 20 (25%) 0 (0%) 2 (3%) 0 (0%) >70%-80% 1 (1%) 13 (16%) 0 (0%) 2 (3%) 0 (0%) >80%-90% 0 (0%) 12 (15%) 0 (0%) 0 (0%) 0 (0%) >90%-100 0 (0%) 7 (9%) 0 (0%) 0 (0%) 0 (0%) 1Respondents could choose one percentage category for each treatment. BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Dear Colleague, RE: Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR): A feasibility study NIHR have asked us to undertake a feasibility study with a view to designing a trial on how best to provide non-invasive ventilation (NIV) for children in hospital with bronchiolitis. As part of this study, we are surveying paediatricians in the UK to find out how these children are currently managed. The questions in this survey will cover the number of children admitted to your hospital with bronchiolitis, the type of NIV intervention(s) used at your hospital and who administers them, and the number of paediatric research staff at your hospital. We would be very grateful if you (or whoever you consider most appropriate within your hospital) could complete the following short survey. If there are any questions that you are unable to answer, there is an option at the end of the survey to suggest who could provide answers on your behalf. Kind Regards Professor Paul McNamara On behalf of the NOVEMBR study team Email: Novembr[email protected] Telephone: 0151 252 5573 / 0151 794 9838 Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice 1 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice 1. Please indicate the name of the hospital where you work* Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice 2. Please provide your job title/role 2 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice 24. How many whole time equivalent (WTE) paediatric research nurses work at your hospital? (If not known, enter NK) 25. On an average shift, how many ward nurses are GCP (Good Clinical Practice) trained? (If not known, enter NK) 26. On an average shift, how many doctors are GCP (Good Clinical Practice) trained? (If not known, enter NK) 14 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice 29. What would enable you to participate in the study at your hospital? (If not known, enter NK) Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice 30. As part of the NOVEMBR feasibility study, we will be conducting a Delphi survey to identify important outcomes for use in future clinical trials. We would greatly appreciate your input. If you are interested in completing the survey, please enter your email address into the comments box below: 16 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice Reminder: If you answered 'yes' to question 6. 'Do you have any local bronchiolitis care pathways and/or guidance?', please email a copy to novembr[email protected]. Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice Name: Email address: Name: Email address: 31. If there are any questions that you have been unable to answer, we would be grateful if you could provide details (name and email address) of anyone who might be able to provide this information. 17 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A Non-invasive ventilation in the management of children with bronchiolitis (NOVEMBR); National Survey of Current Practice Many thanks for taking part in this survey, we greatly appreciate your input! Best wishes, The NOVEMBR team 18 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Paediatrics Open doi: 10.1136/bmjpo-2020-000780:e000780. 4 2020;BMJ Paediatrics Open, et al. Rosala-Hallas A