Summary of main findings
Phase 1a: scoping review
In our scoping review of paediatric ERM literature, we identified that optimal aspects of ERM intervention delivery, timing, content, active ingredients, dose–response relationships, progression and implementation strategies have yet to be established. Multicomponent ‘non-mobility’ and ‘mobility’ ERM interventions were feasible and safe and most involved physical therapy, OT and SLT.
Children under 3 years old were more likely to receive interventions such as cuddles or in-bed mobilisation, whereas non-ventilated children or those aged 3 years and older were more likely to receive mobility interventions involving physical therapy or OT. Importantly, family involvement appeared crucial, and the lack of a well-defined ERM protocol was a significant barrier to ERM implementation. With no clear evidence on the impact of bundles of care or behavioural interventions incorporated within ERM, further research in this area is essential.
Phase 1b: survey of current practice
This national survey of HCPs from UK PICUs identified the importance of ERM as an intervention which participants believe can improve the physical, psychological and cognitive recovery of critically ill or injured infants and children across all ages. Our findings indicated support for ERM, but highlight uncertainty with suitability, variability with the definition of this complex intervention, variation in timing of initiating and which patient groups should receive ERM. Similar to our scoping review, the reported lack of ERM protocols in most (21/26) UK PICUs reinforced a strong requirement for evidence-based standardised protocols with optimal timing, intensity, frequency and duration of ERM. There is a need for flexible protocols to allow for tailoring rather than prescription. Key barriers to ERM delivery were identified (e.g. funding and staffing) and potential clinical (e.g. improved psychological outcomes) and economic (e.g. reduced PICU LOS) benefits to patients and PICUs.
Phase 1c: observational study of early rehabilitation and mobilisation practice
We observed ERM practice in 169 patients across 15 PICUs who reached 9 a.m. on day 3 after PICU admission in our 14-day observation period. Ninety per cent of eligible patients were enrolled using an opt-out consent model. On the first study day (day 3 after PICU admission) 162/169 (96%) of patients received an ERM activity; 87% involved a mobility and 38% an out-of-bed mobility. The rate of ERM activities for patients remained constant across the subsequent 7 days of their PICU admission (or until PICU discharge).
Over the observation period, 3696 ERM episodes delivered 4978 ERM activities across all PICUs. Most were delivered by a registered nurse or parent/family member. Positioning with and without mobility elements accounted for nearly half of all ERM activities. A wide range of ERM activities were reported, but were more likely to be passive or enrichment activities rather than active ERM. ‘Cuddles’ by a family member/nursing staff was the most frequent out-of-bed activity. We identified that family presence significantly increased out-of-bed ERM, although MV, presence of a urinary catheter and pre-existing severe developmental delay were associated with not receiving out-of-bed ERM. Presence of an ERM protocol did not impact the chance of out-of-bed mobility. However, ERM was delivered to nearly all patients, including those of all ages, admission diagnosis and with the highest level of organ dysfunction or organ support.
ERM was delivered safely with a low (<3%) reported rate of AEs per ERM activity. Most AEs did not require any corrective intervention. Of concern was that delirium screening was universally absent in study-participating PICUs and this requires attention. Nursing staff and parents delivered the majority of ERM activities throughout the 24 hours period. Physiotherapists only delivered 10% of ERM although 59% of patients received at least one PT-delivered ERM episode at some point. There was minimal input from other medical, therapy, or support staff reported. Any ERM manual or intervention plan will need to be designed to utilise available staff or require significant increased resources to support them.
Phase 2: paediatric early rehabilitation and mobilisation during intensive care manual development
Our synthesis of the key messages, assumptions and uncertainties that emerged from our prior Phase 1 work showed that ERM is currently defined and enacted in multiple ways. Importantly, people see the potential value for the diverse patient populations within PICU and are willing to support the safe delivery of ERM but are uncertain how best to deliver it. Our three face-to-face workshops with NHS HCPs (n = 18) and one online workshop with international experts (n = 3) helped generate some core guiding principles around the potential shape and content of the intervention. For example, everyone in PICU (doctors, nurses, physiotherapists, and parents) is essential for ERM delivery – everyone should take some ownership. Also, ERM needs to be as inclusive as possible, with a focus on promoting movement and mobility as early as possible and with progressive increases over time. Our review of existing ERM protocols and discussions with healthcare professionals enabled us to develop a prototype ERM manual that was focused both on the safe delivery of ERM for each patient, and on the introduction and embedding of an ERM approach within a PICU. The manual was informed by current evidence, experience, and theory. It offered a flexible, progressive, approach to the delivery of ERM, with resources including essential clinical materials – the ‘bedside bundle’ – that consist of an ERM daily flowchart, patient acuity levels, ERM activity levels, and pause and re-assess criteria. It also included a step-by-step guide to putting ERM into practice – the ‘implementation toolkit’ – that focused on building ERM leadership, generating staff buy-in, making ERM workable, and keeping it going over time.
Phase 3: feasibility trial and implementing evaluation of non-randomised early rehabilitation and mobilisation intervention
All three sites implemented the PERMIT programme as described in the manual. The families were positive about the study recruitment process and all sites successfully recruited the 10-patient target. To achieve ERM delivery, all patients (1) had an acuity level scored (and repeated on 84% of ward rounds) and (2) had an acuity level correctly linked to an ERM activity prescription and then subsequently to a delivered ERM activity. The level of activity was broadly representative of the acuity level.
Other key findings were that a large number of clinically relevant patient outcomes were measured through validated tools and all patients received ERM activities safely using the pause and assess criteria with only two trial reported AEs and no severe AEs. ERM was important for the physical and psychological recovery of the CYP, as well as the psychological well-being of parents/carers supporting their involvement in their child’s care. PERMIT was seen by health professionals and parents as worthwhile, feasible and acceptable. Finally, having access to research delivery support was central to support recruitment, data collection and data entry.
Phase 4: consensus study and trial design
With input from PPIE, parent/family members and multidisciplinary members of the study management group we reviewed and refined the findings from Phases 1, 2 and 3 of PERMIT. We confirmed that a future PERMIT ERM clinical trial was necessary and likely to be feasible with consideration of additional trial design elements. The most suitable trial design for the complex intervention is a clustered stepped-wedge randomised control trial within PICUs across the NHS. The primary outcome requires further consideration. LOV (or days free from ventilation) is a pragmatic compromise on measurable PICU outcome and a likely accurate measure of improvement in critical illness recovery. It would also allow comparison of the PERMIT manual and intervention with the only other similar PICU-wide ERM intervention study, the PICU UP! programme, ongoing in the USA.112 Further consensus work in developing the primary outcome will be required with the UK PCCS-SG and trialists prior to a definitive study proposal. Any future trial will require health economic evaluation in addition to assessment of patient-related outcomes.
Strengths and limitations
Phase 1a: scoping review
We conducted a comprehensive search using broad inclusion criteria, but the risk of publication bias remains. We also acknowledge the inherent limitations of vote-counting used to determine effective ERM interventions since RCTs included in this review were not adequately powered, and findings may not be clinically relevant.
The majority of studies included in this review had design flaws, and varied in the consistency and reporting of interventions or outcomes evaluated. No between-group mean/SDs or effect with precision intervals were ever reported. These outcomes might have different implications on the strength of the evidence when the cost effectiveness of ERM is considered. Lastly, most studies did not provide information about intervention delivery to understand active drivers of successful implementation. Consequently, inferences drawn are based solely on explanatory findings.
Phase 1b: survey
The strength of this survey was an inclusive representation of 90% of UK PICUs and views from the wider MDT. A limitation was the use of a non-validated questionnaire. None or partial responses may indicate poor engagement in the ERM topic, and as with all self-reported surveys, responses indicate reported rather than necessarily actual clinical practice. Finally, the findings represent the views of UK NHS staff and may not be generalisable to other healthcare settings.
Phase 1c: observational study
We observed over half of all UK PICUs, geographically diverse, with varying population characteristics, PICU size, case mix and staffing structures during the two observation periods. However, the types of PICUs may not be generalisable to other UK or non-UK PICUs. To focus observations on early ERM, but to avoid very short-stay PICU patients (e.g. <48 hours), we started observation at 9 a.m. on the third day after PICU admission. ERM practice and delivery to patients in the first 72 hours of PICU stay may also be important in guaranteeing dose and efficacy of intervention. In addition, we stopped observation after 7 days of study observation (day 10 of PICU) or at discharge. Thirty-two per cent (54/169) of our cohort continued to stay in PICU and longer-term PICU care and use of ERM may also be important. Also, ERM may have a role in step-down high-dependency care or ward areas.
We acknowledge the potential risk of observer bias and Hawthorne effect in our study design. ERM activities were listed on the bedside activities document to allow ease of recording. Presence of the documentation or the known process of observation may have affected the amount of ERM delivered to patients during the observation period (e.g. increased number, duration or variety of ERM activities, stimulated by the bedside information).
ERM activities were recorded in the medical records by bedside clinical staff. Research staff extracted this information for our PERMIT CRFs. AEs were self-reported by the clinical team without independent confirmation and therefore may have under- or overestimated the frequency of events or relatedness to the ERM activity; however, the rates identified closely matched those extracted in the scoping review.
We identified a very high rate of ERM activity on study day 1 using the inclusive definition of any ERM. This limited any ability to perform the planned logistic regression modelling to explore patient-, site- or ERM-related factors. In our out-of-bed logistic regression model, due to the small number of patients per site, we were unable to use site as a random effect. Further exploratory analysis of factors affecting different subtypes of ERM are planned and may highlight wider variation in practice across sites.
Phase 2: manual development
A strength of this study was the multiple sources of evidence we used to develop the ERM intervention manual: evidence from a wide range of existing studies, concepts, tools and resources, as well as the experience of diverse practitioners and topic experts. A further strength was that the manual was informed by a range of theories of implementation. However, given the COVID context during the study, we were unable to conduct workshops and interviews with parents and CYP with PICU experience, so we were not at all successful in using their direct experience to shape the ideas within the manual. The work of learning from parents’ experiences was instead undertaken through the process evaluation work in Phase 3.
Phase 3: part 1 feasibility study
A strength of this study was the phased introduction and embedding of a novel intervention (the PERMIT manual) alongside a set of novel trial processes. A further strength was the engagement of staff within and across sites, including those who championed and led the ERM programme, those who delivered ERM, as well as those other staff at the sites not directly involved in bedside ERM delivery. This enabled us to introduce an ERM programme at pace, enrol planned numbers of patients and parents, demonstrate data collection is feasible and the ERM is delivered safely. We were not successful in obtaining timely local site approvals at one site, which meant that the introduction of the ERM programme was delayed. As a result, this site spent relatively little time in each of the phases. Also, when research staff were not available at sites – notably on ward rounds – we did lose some quality and accuracy in some areas of data collection. A health economic evaluation was removed from the feasibility study after the request of the HTA board. Full health economic evaluation and support in a future study are required.
Phase 3: part 2 process evaluation
A strength of our data is the spread of data across methods, as well as across sites and participants. We obtained a comprehensive account of the difficulties of introduction and embedding across the sites. A further strength was the multidisciplinary respondents from each site – including those who championed and led the introduction, those who delivered ERM, as well as those other staff at the sites not directly involved in bedside ERM delivery. This enabled us to document the range of perspectives on problems and tensions around the evolving context and delivery across the sites. Parental accounts were helpful in clarifying trial processes, as well as providing insight into their perspectives of delivering ERM, and were essential to the highlighting of elements to change in future. We were not successful in recruiting parents who had refused consent to the main study for an interview to explore their reasons for declining.
Phase 4: consensus and trial development
The short duration of the Phase 4 study and continued impact of COVID pandemic on PICU health-care staff and parents and families who participated in PERMIT limited the scope of consultation and feedback. Further work with PPIE groups and the PICU clinical community is required to evaluate the definitive primary outcome. This will include additional sample size calculations with more extensive PICANet data after overcoming the cyber-incident at the University of Leeds.
Conclusions and summary of key research recommendations
Early rehabilitation and mobilisation is a complex intervention requiring institutional, departmental and multidisciplinary involvement. We have demonstrated that implementation of the PERMIT manual is acceptable, feasible and can deliver ERM safely to critically unwell and injured infants and CYP within PICUs. Further research in a definitive trial with economic assessment and demonstration of improvement in patient-related outcomes is justified and required.
Implications for healthcare practice
This is a feasibility study and thus has no direct implications for healthcare practice at this stage.