Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B Trial): protocol for a multicentre phase 3 pragmatic clinical and cost-effectiveness randomised trial in the UK.

INTRODUCTION: Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care. METHODS AND ANALYSIS: Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of -2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40-50 UK ICUs. ETHICS AND DISSEMINATION: The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03653832.

Using the TIDieR checklist to describe the intervention of the Sedation and Weaning in Children (SANDWICH) trial.

BACKGROUND: Published reports of complex interventions in randomized controlled trials often lack sufficient detail to allow trial replication and adoption into practice. AIM: The aim of this paper is to describe our experience of using the Template for Intervention Description and Replication (TIDieR) checklist in reporting a recent trial of sedation and ventilation weaning in critically ill children (the Sedation and Weaning in Children [SANDWICH] trial). METHODS: The TIDieR 12-point checklist has been used to detail and describe the specific SANDWICH trial intervention and methods of implementation. RESULTS/DISCUSSION: Overall, we found the checklist a useful tool to direct and ensure consistency of reporting of our complex intervention used in a multi-centre clinical trial. We experienced some minor limitations in classifying training materials and delivery mode into one item because of the overlapping nature of this component. CONCLUSION: Using the TIDieR checklist to report complex interventions tested in trials provides a structured, systematic way of describing necessary detail. This allows clinicians to understand the theory behind the intervention, how it should be delivered, and the resources required. RELEVANCE TO CLINICAL PRACTICE: The SANDWICH intervention had a significant beneficial effect on reducing time on ventilation for children. The detailed description of the team-based intervention will aid replication, implementation and monitoring of fidelity in other paediatric intensive care units.

Does a screening checklist for complex health and social care needs have potential clinical usefulness for predicting unplanned hospital readmissions in intensive care survivors: development and prospective cohort study.

OBJECTIVES: Intensive care (ICU) survivors are at high risk of long-term physical and psychosocial problems. Unplanned hospital readmission rates are high, but the best way to triage patients for interventions is uncertain. We aimed to develop and evaluate a screening checklist to help predict subsequent readmissions or deaths. DESIGN: A checklist for complex health and social care needs (CHSCNs) was developed based on previous research, comprising six items: multimorbidity; polypharmacy; frequent previous hospitalisations; mental health issues; fragile social circumstances and impaired activities of daily living. Patients were considered to have CHSCNs if two or more were present. We prospectively screened all ICU discharges for CHSCNs for 12 months. SETTING: ICU, Royal Infirmary, Edinburgh, UK. PARTICIPANTS: ICU survivors over a 12-month period (1 June 2018 and 31 May 2019). INTERVENTIONS: None. OUTCOME MEASURE: Readmission or death in the community within 3 months postindex hospital discharge. RESULTS: Of 1174 ICU survivors, 937 were discharged alive from the hospital. Of these 253 (27%) were classified as having CHSCNs. In total 28% (266/937) patients were readmitted (N=238) or died (N=28) within 3 months. Among CHSCNs patients 45% (n=115) patients were readmitted (N=105) or died (N=10). Patients without CHSCNs had a 22% readmission (N=133) or death (N=18) rate. The checklist had: sensitivity 43% (95% CI 37% to 49%), specificity 79% (95% CI 76% to 82%), positive predictive value 45% (95% CI 41% to 51%), and negative predictive value 78% (95% CI 76% to 80%). Relative risk of readmission/death for patients with CHSCNs was 2.06 (95% CI 1.69 to 2.50), indicating a pretest to post-test probability change of 28%-45%. The checklist demonstrated high inter-rater reliability (percentage agreement ≥87% for all domains; overall kappa, 0.84). CONCLUSIONS: Early evaluation of a screening checklist for CHSCNs at ICU discharge suggests potential clinical usefulness, but this requires further evaluation as part of a care pathway.

Challenges and barriers to optimising sedation in intensive care: a qualitative study in eight Scottish intensive care units.

OBJECTIVES: Various strategies to promote light sedation are highly recommended in recent guidelines, as deep sedation is associated with suboptimum patient outcomes. Yet, the challenges met by clinicians in delivering high-quality analgosedation is rarely addressed. As part of the evaluation of a cluster-randomised quality improvement trial in eight Scottish intensive care units (ICUs), we aimed to understand the challenges to optimising sedation in the Scottish ICU settings prior to the trial. This article reports on the findings. DESIGN: A qualitative exploratory design: We conducted focus groups (FG) with clinicians during the preintervention period. Setting and participants: Eight Scottish ICUs. Nurses, physiotherapists and doctors working in each ICU volunteered to participate. FG were recorded and verbatim transcribed and inserted in NVivo V.10 for analysis. Qualitative thematic analysis was undertaken to develop emergent themes from the patterns identified in relation to sedation practice. Ethical approval was secured by Scotland A Research ethics committee. RESULTS: Three themes emerged from the inductive analysis: (a) a recent shift in sedation practice, (b) uncertainty in decision-making and (c) system-level factors including the ICU environment, organisational factors and educational gaps. Clinicians were challenged daily to manage agitated or difficult-to-sedate patients in the era of a progressive mantra of 'just sedate less' imposed by the pain-agitation-delirium guidelines. CONCLUSIONS: The current implementation of guidelines does not support behaviour change strategies to allow a patient-focused approach to sedation management, which obstructs optimum sedation-analgesia management. Recognition of the various challenges when mandating less sedation needs to be considered and novel sedation-analgesia strategies should allow a system-level approach to improve sedation-analgesia quality. DESIST REGISTRATION NUMBER: NCT01634451.

Unplanned early hospital readmission among critical care survivors: a mixed methods study of patients and carers.

BACKGROUND: Many intensive care (ICU) survivors experience early unplanned hospital readmission, but the reasons and potential prevention strategies are poorly understood. We aimed to understand contributors to readmissions from the patient/carer perspective. METHODS: This is a mixed methods study with qualitative data taking precedence. Fifty-eight ICU survivors and carers who experienced early unplanned rehospitalisation were interviewed. Thematic analysis was used to identify factors contributing to readmissions, and supplemented with questionnaire data measuring patient comorbidity and carer strain, and importance rating scales for factors that contribute to readmissions in other patient groups. Data were integrated iteratively to identify patterns, which were discussed in five focus groups with different patients/carers who also experienced readmissions. Major patterns and contexts in which unplanned early rehospitalisation occurred in ICU survivors were described. RESULTS: Interviews suggested 10 themes comprising patient-level and system-level issues. Integration with questionnaire data, pattern exploration and discussion at focus groups suggested two major readmission contexts. A 'complex health and psychosocial needs' context occurred in patients with multimorbidity and polypharmacy, who frequently also had significant psychological problems, mobility issues, problems with specialist aids/equipment and fragile social support. These patients typically described inadequate preparation for hospital discharge, poor communication between secondary/primary care, and inadequate support with psychological care, medications and goal setting. This complex multidimensional situation contrasted markedly with the alternative 'medically unavoidable' readmission context. In these patients medical issues/complications primarily resulted in hospital readmission, and the other issues were absent or not considered important. CONCLUSIONS: Although some readmissions are medically unavoidable, for many ICU survivors complex health and psychosocial issues contribute concurrently to early rehospitalisation. Care pathways that anticipate and institute anticipatory multifaceted support for these patients merit further development and evaluation.

Algorithm for Quantifying Frontal EMG Responsiveness for Sedation Monitoring.

INTRODUCTION: To study stimulation-related facial electromyographic (FEMG) activity in intensive care unit (ICU) patients, develop an algorithm for quantifying the FEMG activity, and to optimize the algorithm for monitoring the sedation state of ICU patients. METHODS: First, the characteristics of FEMG response patterns related to vocal stimulation of 17 ICU patients were studied. Second, we collected continuous FEMG data from 30 ICU patients. Based on these data, we developed the Responsiveness Index (RI) algorithm that quantifies FEMG responses. Third, we compared the RI values with clinical sedation level assessments and adjusted algorithm parameters for best performance. RESULTS: In patients who produced a clinically observed response to the vocal stimulus, the poststimulus FEMG power was 0.33 µV higher than the prestimulus power. In nonresponding patients, there was no difference. The sensitivity and specificity of the developed RI for detecting deep sedation in the subgroup with low probability of encephalopathy were 0.90 and 0.79, respectively. CONCLUSION: Consistent FEMG patterns were found related to standard stimulation of ICU patients. A simple and robust algorithm was developed and good correlation with clinical sedation scores achieved in the development data.

A rehabilitation intervention to promote physical recovery following intensive care: a detailed description of construct development, rationale and content together with proposed taxonomy to capture processes in a randomised controlled trial.

BACKGROUND: Increasing numbers of patients are surviving critical illness, but survival may be associated with a constellation of physical and psychological sequelae that can cause ongoing disability and reduced health-related quality of life. Limited evidence currently exists to guide the optimum structure, timing, and content of rehabilitation programmes. There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period. This paper describes the construct development for a complex rehabilitation intervention intended to promote physical recovery following critical illness. The intervention is currently being evaluated in a randomised trial (ISRCTN09412438; funder Chief Scientists Office, Scotland). METHODS: The intervention was developed using the Medical Research Council (MRC) framework for developing complex healthcare interventions. We ensured representation from a wide variety of stakeholders including content experts from multiple specialties, methodologists, and patient representation. The intervention construct was initially based on literature review, local observational and audit work, qualitative studies with ICU survivors, and brainstorming activities. Iterative refinement was aided by the publication of a National Institute for Health and Care Excellence guideline (No. 83), publicly available patient stories (Healthtalkonline), a stakeholder event in collaboration with the James Lind Alliance, and local piloting. Modelling and further work involved a feasibility trial and development of a novel generic rehabilitation assistant (GRA) role. Several rounds of external peer review during successive funding applications also contributed to development. RESULTS: The final construct for the complex intervention involved a dedicated GRA trained to pre-defined competencies across multiple rehabilitation domains (physiotherapy, dietetics, occupational therapy, and speech/language therapy), with specific training in post-critical illness issues. The intervention was from ICU discharge to 3 months post-discharge, including inpatient and post-hospital discharge elements. Clear strategies to provide information to patients/families were included. A detailed taxonomy was developed to define and describe the processes undertaken, and capture them during the trial. The detailed process measure description, together with a range of patient, health service, and economic outcomes were successfully mapped on to the modified CONSORT recommendations for reporting non-pharmacologic trial interventions. CONCLUSIONS: The MRC complex intervention framework was an effective guide to developing a novel post-ICU rehabilitation intervention. Combining a clearly defined new healthcare role with a detailed taxonomy of process and activity enabled the intervention to be clearly described for the purpose of trial delivery and reporting. These data will be useful when interpreting the results of the randomised trial, will increase internal and external trial validity, and help others implement the intervention if the intervention proves clinically and cost effective.

A randomised controlled trial evaluating a rehabilitation complex intervention for patients following intensive care discharge: the RECOVER study.

INTRODUCTION: Patients who survive an intensive care unit admission frequently suffer physical and psychological morbidity for many months after discharge. Current rehabilitation pathways are often fragmented and little is known about the optimum method of promoting recovery. Many patients suffer reduced quality of life. METHODS AND ANALYSIS: The authors plan a multicentre randomised parallel group complex intervention trial with concealment of group allocation from outcome assessors. Patients who required more than 48 h of mechanical ventilation and are deemed fit for intensive care unit discharge will be eligible. Patients with primary neurological diagnoses will be excluded. Participants will be randomised into one of the two groups: the intervention group will receive standard ward-based care delivered by the NHS service with additional treatment by a specifically trained generic rehabilitation assistant during ward stay and via telephone contact after hospital discharge and the control group will receive standard ward-based care delivered by the current NHS service. The intervention group will also receive additional information about their critical illness and access to a critical care physician. The total duration of the intervention will be from randomisation to 3 months postrandomisation. The total duration of follow-up will be 12 months from randomisation for both groups. The primary outcome will be the Rivermead Mobility Index at 3 months. Secondary outcomes will include measures of physical and psychological morbidity and function, quality of life and survival over a 12-month period. A health economic evaluation will also be undertaken. Groups will be compared in relation to primary and secondary outcomes; quantitative analyses will be supplemented by focus groups with patients, carers and healthcare workers. ETHICS AND DISSEMINATION: Consent will be obtained from patients and relatives according to patient capacity. Data will be analysed according to a predefined analysis plan. TRIAL REGISTRATION: The trial is registered as ISRCTN09412438 and funded by the Chief Scientist Office, Scotland.

A longitudinal qualitative exploration of healthcare and informal support needs among survivors of critical illness: the RELINQUISH protocol.

INTRODUCTION AND BACKGROUND: Survival following critical illness is associated with a significant burden of physical, emotional and psychosocial morbidity. Recovery can be protracted and incomplete, with important and sustained effects upon everyday life, including family life, social participation and return to work. In stark contrast with other critically ill patient groups (eg, those following cardiothoracic surgery), there are comparatively few interventional studies of rehabilitation among the general intensive care unit patient population. This paper outlines the protocol for a sub study of the RECOVER study: a randomised controlled trial evaluating a complex intervention of enhanced ward-based rehabilitation for patients following discharge from intensive care. METHODS AND ANALYSIS: The RELINQUISH study is a nested longitudinal, qualitative study of family support and perceived healthcare needs among RECOVER participants at key stages of the recovery process and at up to 1 year following hospital discharge. Its central premise is that recovery is a dynamic process wherein patients' needs evolve over time. RELINQUISH is novel in that we will incorporate two parallel strategies into our data analysis: (1) a pragmatic health services-oriented approach, using an a priori analytical construct, the 'Timing it Right' framework and (2) a constructivist grounded theory approach which allows the emergence of new themes and theoretical understandings from the data. We will subsequently use Qualitative Health Needs Assessment methodology to inform the development of timely and responsive healthcare interventions throughout the recovery process. ETHICS AND DISSEMINATION: The protocol has been approved by the Lothian Research Ethics Committee (protocol number HSRU011). The study has been added to the UK Clinical Research Network Database (study ID. 9986). The authors will disseminate the findings in peer reviewed publications and to relevant critical care stakeholder groups.

Rehabilitation after critical illness: could a ward-based generic rehabilitation assistant promote recovery?

AIM: The aim of this paper is to explore issues surrounding the implementation of a generic rehabilitation assistant (GRA) to provide ward-based rehabilitation after critical illness. BACKGROUND: Following critical illness a range of both physical and psychological problems can occur that include muscle wasting and weakness, fatigue, reduced appetite, post-traumatic stress, anxiety and depression. Limited research exists evaluating the provision of rehabilitation to this patient group. This paper explores one possible service delivery model providing ward-based rehabilitation after critical illness. The model explored is a GRA working in conjunction with ward-based staff. RESULTS: We describe how a GRA worked effectively with ward-based teams to provide additional rehabilitation in the period after discharge from intensive care. Benefits included greater continuity of care that was flexible to the individual needs of patients. Some aspects of the role were challenging for the GRA and highlighted the need for good communication skills. A need for comprehensive training of the GRA was demonstrated. CONCLUSIONS: Our experience demonstrates that it is feasible to deliver ward-based rehabilitation after critical illness using the GRA service delivery model. RELEVANCE TO CLINICAL PRACTICE: This model of service delivery offers the potential to improve outcomes for patients after a critical illness. Further research evaluating this model of care is required before implementation into clinical practice.