Virtual Post-Intensive-Care Rehabilitation for Survivors of COVID-19: A Service Evaluation.

AIM: The objective of this study is to evaluate the safety, utilisation, and effectiveness of a novel, virtual rehabilitation programme for survivors of SARS­CoV­2 infection (COVID-19) and intensive care admission. METHODS: A service evaluation was performed. Adults admitted to a United Kingdom intensive care unit with COVID-19-induced respiratory failure and surviving hospital discharge were invited to an eight-week rehabilitation programme. The programme consisted of virtually delivered exercise classes and support groups led by critical care physiotherapists and follow-up nurses. RESULTS: Thirty-eight of 76 eligible patients (50%) agreed to participate, of which 28 (74%) completed the rehabilitation programme. On completion of the rehabilitation programme, there were significant improvements in exercise capacity (one-minute sit-to-stand test; 20 stands vs. 25 stands, p < 0.001), perceived breathlessness (Medical Research Council dyspnoea scale; 3 vs. 2 p < 0.001), shoulder disability (Quick Dash; 43 vs. 19 p = 0.001), anxiety (Hospital Anxiety Depression Scale; 4 vs. 3 p = 0.021), depression (Hospital Anxiety Depression Scale; 4 vs. 2.5 p = 0.010), and psychological distress (Intensive Care Psychological Assessment Tool; 3 vs. 2 p = 0.002). No adverse events or injuries were recorded during the programme. CONCLUSION: It is feasible to recruit and retain survivors of COVID-19-induced respiratory failure for virtual post-intensive-care rehabilitation. It appears that the virtual rehabilitation programme is safe and improves physical and psychological morbidity.

Comparing rehabilitation outcomes for patients admitted to the intensive care unit with COVID-19 requiring mechanical ventilation during the first two waves of the pandemic: A service evaluation.

OBJECTIVES: To compare rehabilitation outcomes of patients admitted to the intensive care unit with COVID-19 and mechanically ventilated during wave 1 and 2, receiving two different models of physiotherapy delivery. METHODS: Adults admitted to the intensive care unit between October-March 2021 (wave 2) with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. During wave 2, rehabilitation was provided by physiotherapists over five days, with only emergency respiratory physiotherapy delivered at weekends. Rehabilitation status was measured daily using the Manchester Mobility Score to identify time taken to first mobilise and highest level of mobility achieved at ICU discharge. Outcomes were compared to data previously published from the same ICU during 'wave 1' (March-April 2020) when a seven-day rehabilitation physiotherapy service was provided. RESULTS: A total of n = 291 patients were included in analysis; 110 from wave 1, and 181 from wave 2. Patient characteristics and medical management were similar between waves. Mean ± SD time to first mobilise was slower in wave 2 (15 ± 11 days vs 14 ± 7 days), with overall mobility scores lower at both ICU (MMS 5 (Step transferring) vs MMS 4 (standing practice) (4), p < 0.05) and hospital (MMS 7 (Mobile > 30 m MMS) vs MMS 6 (Mobile < 30 m MMS), p < 0.0001) discharge. Significantly more patients in wave 2 required ongoing rehabilitation either at home or as an inpatient compared to wave 1 (81 % vs 49 %, p = 0.003). CONCLUSION: The change in physiotherapy staff provision from a seven-day rehabilitation service during wave 1 to a five day rehabilitation service with emergency respiratory physio only at weekends in wave 2 was associated with delayed time to first mobilise, lower levels of mobility at both intensive care unit and hospital discharge and higher requirement for ongoing rehabilitation at the point of hospital discharge.

Increase in recruitment upon integration of trial into a clinical care pathway: an observational study.

INTRODUCTION: Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers. METHODS: A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP. RESULTS: On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence. DISCUSSION: Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.

Rehabilitation Levels in Patients with COVID-19 Admitted to Intensive Care Requiring Invasive Ventilation. An Observational Study.

Rationale: Patients with severe coronavirus disease (COVID-19) have complex organ support needs that necessitate prolonged stays in the intensive care unit (ICU), likely to result in a high incidence of neuromuscular weakness and loss of well-being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations.Objectives: To describe the demographics, clinical status, level of rehabilitation, and mobility status at ICU discharge of patients with COVID-19.Methods: Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. Rehabilitation status was measured daily using the Manchester Mobility Score to identify the time taken to first mobilize (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge.Results: A total of n = 177 patients were identified, of whom n = 110 survived to ICU discharge and were included in the subsequent analysis. While on ICU, patients required prolonged periods of mechanical ventilation (mean 19 ± 10 d), most received neuromuscular blockade (90%) and 67% were placed in the prone position on at least one occasion. The mean ± standard deviation time to first mobilize was 14 ± 7 days, with a median Manchester Mobility Score at ICU discharge of 5 (interquartile range: 4-6), which represents participants able to stand and step around to a chair with or without assistance. Time to mobilize was significantly longer in those with higher body mass index (P < 0.001), and older patients (P = 0.012) and those with more comorbidities (P = 0.017) were more likely to require further rehabilitation after discharge.Conclusions: The early experience of the COVID-19 pandemic in the United Kingdom resembles the experience in other countries, with high acuity of illness and prolonged period of mechanical ventilation required for those patients admitted to the ICU. Although the time to commence rehabilitation was delayed owing to this severity of illness, rehabilitation was possible within the ICU and led to increased levels of mobility from waking before ICU discharge.Clinical trial registered with ClinicalTrials.gov (NCT04396197).

Assembly Line ICU: what the Long Shops taught us about managing surge capacity for COVID-19.

OBJECTIVES: To safely expand and adapt the normal workings of a large critical care unit in response to the COVID-19 pandemic. METHODS: In April 2020, UK health systems were challenged to expand critical care capacity rapidly during the first wave of the COVID-19 pandemic so that they could accommodate patients with respiratory and multiple organ failure. Here, we describe the preparation and adaptive responses of a large critical care unit to the oncoming burden of disease. Our changes were similar to the revolution in manufacturing brought about by 'Long Shops' of 1853 when Richard Garrett and Sons of Leiston started mass manufacture of traction engines. This innovation broke the whole process into smaller parts and increased productivity. When applied to COVID-19 preparations, an assembly line approach had the advantage that our ICU became easily scalable to manage an influx of additional staff as well as the increase in admissions. Healthcare professionals could be replaced in case of absence and training focused on a smaller number of tasks. RESULTS: Compared with the equivalent period in 2019, the ICU provided 30.9% more patient days (2599 to 3402), 1845 of which were ventilated days (compared with 694 in 2019, 165.8% increase) while time from first referral to ICU admission reduced from 193.8±123.8 min (±SD) to 110.7±76.75 min (±SD). Throughout, ICU maintained adequate capacity and also accepted patients from neighbouring hospitals. This was done by managing an additional 205 doctors (70% increase), 168 nurses who had previously worked in ICU and another 261 nurses deployed from other parts of the hospital (82% increase).Our large tertiary hospital ensured a dedicated non-COVID ICU was staffed and equipped to take regional emergency referrals so that those patients requiring specialist surgery and treatment were treated throughout the COVID-19 pandemic. CONCLUSIONS: We report how the challenge of managing a huge influx of patients and redeployed staff was met by deconstructing ICU care into its constituent parts. Although reported from the largest colocated ICU in the UK, we believe that this offers solutions to ICUs of all sizes and may provide a generalisable model for critical care pandemic surge planning.

An interdisciplinary approach to the management of critically ill patients during covid-19 pandemic; an experience of a university hospital in England.

COVID-19 pandemic presents significant challenges in delivering safe and efficient patient care, especially during the surges. In all health care systems, provision of available critical care facilities is a scarce resource, even in normal times. Problematic is not just the limitation of physical spaces in intensive care units, but also the availability of trained personnel. The critical care model, developed in Queen Elizabeth Hospital Birmingham to cope with the surge of COVID-19 patients, is based on early implementation of an interdisciplinary approach and extensive cooperation between the branches of practice, allowing to address both challenges. The main pillars are early upskilling of non-critical care staff, creation of safe, streamlined clinical pathways, adjustment of the physical layout of critical care units and comprehensive cross-town cooperation allowing to accommodate an increased number of patients, requiring intensive care. The model was well tested in clinical practice, enabling the hospital to increase the critical care footprint by more than 200% during the pandemic's surge between March and May 2020.

Analgesia of Patients with Multiple Rib Fractures in Critical Care: A Survey of Healthcare Professionals in the UK.

INTRODUCTION: Good analgesia has been shown to reduce the risk of pneumonia, chronic pain, and mortality in patients with multiple rib fractures (MRFs). This survey explores the current analgesic practice in the UK, protocol use, barriers to provision, and physician preferences. MATERIALS AND METHODS: A web-based survey was distributed nationally to an enriched cohort of clinicians working in UK trauma units with an interest in MRF management. RESULTS: Seventy-nine healthcare professionals responded. A third (31.4%) reported that their department had a rib fracture pain protocol, 52.9% did not, and 15.7% were unsure. Significantly more respondents reported adequate pain control when a hospital protocol was present compared to when not (χ 2, p < 0.01). Inadequate analgesia, a poor cough, and inability to breathe deeply were the commonest complications reported by 81.4, 78.6, and 65.7%, respectively. Patient-controlled analgesia (PCA) was the most commonly used form of analgesia (38.6%) followed by thoracic epidural (TEA) (30.0%) and continuous opioid infusion (18.6%). However, TEA was the preferred method of analgesia among respondents (37.1%) followed by serratus block (21.4%), paravertebral block (17.1%), and PCA (14.3%). DISCUSSION: There is considerable variation among physicians in their current use of analgesic modalities, with opiate-based methods predominating despite a physician preference for regional techniques. Thoracic epidurals are preferred by physicians but of limited use as a result of contraindications, time pressures, and staff skill mix. Pain control is reported to be better handled when protocols are present. Further research focusing on currently utilized regional techniques is required in order to produce a validated standardized national protocol that is informed by the current practice, the evidence base, and limitations to service provision. KEY MESSAGES: There is considerable variation among physicians in their current use of analgesic modalities. Opiate-based methods dominate for thoracic trauma despite a physician preference for regional techniques, which can be challenging in this cohort due to contraindications, staff skill mix, and time pressures. Inadequate analgesia is common but is better managed when pain management protocols are available. HOW TO CITE THIS ARTICLE: Beard L, Holt B, Snelson C, Parcha C, Smith FG, Veenith T. Analgesia of Patients with Multiple Rib Fractures in Critical Care: A Survey of Healthcare Professionals in the UK. Indian J Crit Care Med 2020;24(3):184-189.

Protocolised non-invasive compared with invasive weaning from mechanical ventilation for adults in intensive care: the Breathe RCT.

BACKGROUND: Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. DESIGN: Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis. SETTING: A total of 51 critical care units across the UK. PARTICIPANTS: Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. INTERVENTIONS: Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient's condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient's condition. MAIN OUTCOME MEASURES: The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. RESULTS: A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57-351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5-297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2-11 days) vs. non-invasive weaning 1 day (IQR 0-7 days); adjusted mean difference -3.1 days, 95% CI -5.75 to -0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. CONCLUSIONS: A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections. FUTURE WORK: In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV? TRIAL REGISTRATION: Current Controlled Trials ISRCTN15635197. 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. 23, No. 48. See the NIHR Journals Library website for further project information.

Patients who become very unwell may require help from a breathing machine. This requires the patient to be given drugs to put them to sleep (sedation) and have a tube placed through their mouth directly into the windpipe (tube ventilation). This can be life-saving, but may cause harm if used for long periods of time. Non-invasive ventilation (mask ventilation) provides breathing support through a mask that covers the face. Mask ventilation has several advantages over tube ventilation, such as less need for sedation, and it enables the patient to cough and communicate. In previous studies, switching patients from tube to mask ventilation when they start to get better seemed to improve survival rates and reduce complications. The Breathe trial tested if using a protocol to remove tube ventilation and replace it with mask ventilation is better than continuing with tube ventilation until the patient no longer needs breathing machine support. The trial recruited 364 patients. Half of these patients were randomly selected to have the tube removed and replaced with mask ventilation and half were randomly selected to continue with tube ventilation until they no longer needed breathing machine support. The mask group spent 3 fewer days receiving tube ventilation, although the overall time needing breathing machine help (mask and tube) did not change. Fewer patients in the mask group needed antibiotics for chest infections. After removing the tube, twice as many patients needed the tube again in the mask group as in the tube group. There were no differences between the groups in the number of adverse (harm) events or the number of patients who survived to leave hospital. Mask ventilation was no more expensive than tube ventilation. In conclusion, mask ventilation may be an effective alternative to continued tube ventilation when patients start to get better in intensive care.

Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients.

Among long-stay critically ill patients in the adult intensive care unit (ICU), there are often marked changes in the complexity of the gut microbiota. However, it remains unclear whether such patients might benefit from enhanced surveillance or from interventions targeting the gut microbiota or the pathogens therein. We therefore undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses. Two-thirds of the patients experienced a marked drop in gut microbial diversity (to an inverse Simpson's index of <4) at some stage during their stay in the ICU, often accompanied by the absence or loss of potentially beneficial bacteria. Intravenous administration of the broad-spectrum antimicrobial agent meropenem was significantly associated with loss of gut microbial diversity, but the administration of other antibiotics, including piperacillin/tazobactam, failed to trigger statistically detectable changes in microbial diversity. In three-quarters of ICU patients, we documented episodes of gut domination by pathogenic strains, with evidence of cryptic nosocomial transmission of Enterococcus faecium. In some patients, we also saw an increase in the relative abundance of apparent commensal organisms in the gut microbiome, including the archaeal species Methanobrevibacter smithii. In conclusion, we have documented a dramatic absence of microbial diversity and pathogen domination of the gut microbiota in a high proportion of critically ill patients using shotgun metagenomics.

Patient experience and reflective learning (PEARL): a mixed methods protocol for staff insight development in acute and intensive care medicine in the UK.

INTRODUCTION: Patient and staff experiences are strongly influenced by attitudes and behaviours, and provide important insights into care quality. Patient and staff feedback could be used more effectively to enhance behaviours and improve care through systematic integration with techniques for reflective learning. We aim to develop a reflective learning framework and toolkit for healthcare staff to improve patient, family and staff experience. METHODS & ANALYSIS: Local project teams including staff and patients from the acute medical units (AMUs) and intensive care units (ICUs) of three National Health Service trusts will implement two experience surveys derived from existing instruments: a continuous patient and relative survey and an annual staff survey. Survey data will be supplemented by ethnographic interviews and observations in the workplace to evaluate barriers to and facilitators of reflective learning. Using facilitated iterative co-design, local project teams will supplement survey data with their experiences of healthcare to identify events, actions, activities and interventions which promote personal insight and empathy through reflective learning. Outputs will be collated by the central project team to develop a reflective learning framework and toolkit which will be fed back to the local groups for review, refinement and piloting. The development process will be mapped to a conceptual theory of reflective learning which combines psychological and pedagogical theories of learning, alongside theories of behaviour change based on capability, opportunity and motivation influencing behaviour. The output will be a locally-adaptable workplace-based toolkit providing guidance on using reflective learning to incorporate patient and staff experience in routine clinical activities. ETHICS & DISSEMINATION: The PEARL project has received ethics approval from the London Brent Research Ethics Committee (REC Ref 16/LO/224). We propose a national cluster randomised step-wedge trial of the toolkit developed for large-scale evaluation of impact on patient outcomes.

Introducing early and structured rehabilitation in critical care: A quality improvement project.

OBJECTIVES: To assess the potential impact of introducing an already established and effective programme of rehabilitation within a critical care unit in a different organisation. DESIGN: Fifteen-month prospective before/after quality improvement project. SETTING: Seven-bed mixed dependency critical care unit. PARTICIPANTS: 209 patients admitted to critical care for ≥4 days. INTERVENTION: A multi-faceted quality improvement project focussed on changing structure and overcoming local barriers to increase levels of rehabilitation within critical care. MAIN OUTCOME MEASURE: Proportion of patients mobilised within critical care, time to first mobilise and highest level of mobility achieved within critical care. RESULTS: Compared to before the quality improvement project, significantly more patients mobilised within critical care (92% vs 73%, p = 0.003). This resulted in a significant reduction in time to 1st mobilisation (2 vs 3.5 days, P < 0.001), particularly for those patients ventilated ≥4 days (3 vs 14 days) and higher mobility scores at the point of critical care discharge (Manchester mobility score 5 vs 4, p = 0.019). CONCLUSION: The results from this quality improvement project demonstrate the positive impact of introducing a programme of early and structured rehabilitation to a critical care unit within a different organisation. This could provide a framework for introducing similar programmes to other critical care units nationally.

Effect of Protocolized Weaning With Early Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure: The Breathe Randomized Clinical Trial.

Importance: In adults in whom weaning from invasive mechanical ventilation is difficult, noninvasive ventilation may facilitate early liberation, but there is uncertainty about its effectiveness in a general intensive care patient population. Objective: To investigate among patients with difficulty weaning the effects of protocolized weaning with early extubation to noninvasive ventilation on time to liberation from ventilation compared with protocolized invasive weaning. Design, Setting, and Participants: Randomized, allocation-concealed, open-label, multicenter clinical trial enrolling patients between March 2013 and October 2016 from 41 intensive care units in the UK National Health Service. Follow-up continued until April 2017. Adults who received invasive mechanical ventilation for more than 48 hours and in whom a spontaneous breathing trial failed were enrolled. Interventions: Patients were randomized to receive either protocolized weaning via early extubation to noninvasive ventilation (n = 182) or protocolized standard weaning (continued invasive ventilation until successful spontaneous breathing trial, followed by extubation) (n = 182). Main Outcomes and Measures: Primary outcome was time from randomization to successful liberation from all forms of mechanical ventilation among survivors, measured in days, with the minimal clinically important difference defined as 1 day. Secondary outcomes were duration of invasive and total ventilation (days), reintubation or tracheostomy rates, and survival. Results: Among 364 randomized patients (mean age, 63.1 [SD, 14.8] years; 50.5% male), 319 were evaluable for the primary effectiveness outcome (41 died before liberation, 2 withdrew, and 2 were discharged with ongoing ventilation). The median time to liberation was 4.3 days in the noninvasive group vs 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% CI, 0.89-1.40). Competing risk analysis accounting for deaths had a similar result (adjusted hazard ratio, 1.1; 95% CI, 0.86-1.34). The noninvasive group received less invasive ventilation (median, 1 day vs 4 days; incidence rate ratio, 0.6; 95% CI, 0.47-0.87) and fewer total ventilator days (median, 3 days vs 4 days; incidence rate ratio, 0.8; 95% CI, 0.62-1.0). There was no significant difference in reintubation, tracheostomy rates, or survival. Adverse events occurred in 45 patients (24.7%) in the noninvasive group compared with 47 (25.8%) in the invasive group. Conclusions and Relevance: Among patients requiring mechanical ventilation in whom a spontaneous breathing trial had failed, early extubation to noninvasive ventilation did not shorten time to liberation from any ventilation. Trial Registration: ISRCTN Identifier: ISRCTN15635197.

Association Between Hospital Volume and Mortality in Status Epilepticus: A National Cohort Study.

OBJECTIVES: In various medical and surgical conditions, research has found that centers with higher patient volumes have better outcomes. This relationship has not previously been explored for status epilepticus. This study sought to examine whether centers that see higher volumes of patients with status epilepticus have lower in-hospital mortality than low-volume centers. DESIGN: Cohort study, using 2010-2015 data from the nationwide Case Mix Programme database of the U.K.'s Intensive Care National Audit and Research Centre. SETTING: Greater than 90% of ICUs in United Kingdom, Wales, and Northern Ireland. PATIENTS: Twenty-thousand nine-hundred twenty-two adult critical care admissions with a primary or secondary diagnosis of status epilepticus or prolonged seizure. INTERVENTIONS: Annual hospital status epilepticus admission volume. MEASUREMENTS AND MAIN RESULTS: We used multiple logistic regression to evaluate the association between hospital annual status epilepticus admission volume and in-hospital mortality. Hospital volume was modeled as a nonlinear variable using restricted cubic splines, and generalized estimating equations with robust SEs were used to account for clustering by institution. There were 2,462 in-hospital deaths (11.8%). There was no significant association between treatment volume and in-hospital mortality for status epilepticus (p = 0.54). This conclusion was unchanged across a number of subgroup and sensitivity analyses, although we lacked data on seizure duration and medication use. Secondary analyses suggest that many high-risk patients were already transferred from low- to high-volume centers. CONCLUSIONS: We find no evidence that higher volume centers are associated with lower mortality in status epilepticus overall. It is likely that national guidelines and local pathways in the United Kingdom allow efficient patient transfer from smaller centers like district general hospitals to provide satisfactory patient care in status epilepticus. Future research using more granular data should explore this association for the subgroup of patients with refractory and superrefractory status epilepticus.

Innate and adaptive immune dysregulation in critically ill ICU patients.

This study aimed to evaluate whether ICU patients who developed persistent critical illness displayed an immune profile similar to an aged immune phenotype and any associations with patient outcomes. Twenty two critically ill ICU patients (27-76 years, 15 males), at day 5 of mechanical ventilation, and 22 healthy age-matched controls (27-77 years, 13 males) were recruited. Frequency and phenotype of innate and adaptive immune cells and telomere length in peripheral blood mononuclear cells (PBMCs) were measured. An elevated granulocyte count (p < 0.0001), increased numbers of immature granulocytes (p < 0.0001), increased CD16++ve monocytes (p = 0.003) and CD14+ve HLADRdim/low monocytes (p = 0.004) and lower NK cell numbers (p = 0.007) were observed in ICU patients compared to controls. Critically ill patients also had lower numbers of total T lymphocytes (p = 0.03), naïve CD4 T cells (p = 0.003) and PTK7+ve recent thymic emigrants (p = 0.002), and increased senescent CD28-ve CD57+ve CD4 T cells (p = 0.02), but there was no difference in PBMC telomere length. Regulatory immune cell frequency was affected with reduced circulating CD19+veCD24hiCD38hi regulatory B cells (p = 0.02). However, only a raised neutrophil:lymphocyte ratio and reduced frequency of CD14+ve HLADRdim/low monocytes were associated with poor outcomes. We conclude that persistent critical illness results in changes to immune cell phenotype only some of which are similar to that seen in physiological ageing of the immune system.

Earlier and enhanced rehabilitation of mechanically ventilated patients in critical care: A feasibility randomised controlled trial.

BACKGROUND: Systematic reviews of early rehabilitation within intensive care units have highlighted the need for robust multi-centre randomised controlled trials with longer term follow up. This trial aims to explore the feasibility of earlier and enhanced rehabilitation for patients mechanically ventilated for ≥5days and to assess the impact on possible long term outcome measures for use in a definitive trial. METHODS: Patients admitted to a large UK based intensive care unit and invasively ventilated for ≥5days were randomised to the rehabilitation intervention or standard care on a 1:1 basis, stratified by age and SOFA score. The rehabilitation intervention involved a structured programme, with progression along a functionally based mobility protocol according to set safety criteria. RESULTS: 103 out of 128 eligible patients were recruited into the trial, achieving an initial recruitment rate of 80%. Patients in the intervention arm mobilized significantly earlier (8days vs 10 days, p=0.035), at a more acute phase of illness (SOFA 6 vs 4, p<0.05) and reached a higher level of mobility at the point of critical care discharge (MMS 7 vs 5, p<0.01). CONCLUSION: We have demonstrated the feasibility of introducing a structured programme of rehabilitation for patients admitted to critical care.

A comparison of earlier and enhanced rehabilitation of mechanically ventilated patients in critical care compared to standard care (REHAB): study protocol for a single-site randomised controlled feasibility trial.

BACKGROUND: Mortality from critical illness is improving, but survivors suffer from prolonged weakness and psychological and cognitive impairments. Maximising the recovery after critical illness has been highlighted as a research priority, especially in relation to an ageing population who present with higher rates of pre-morbid disability. Small studies have shown that starting rehabilitation early within the intensive care unit (ICU) improves short-term outcomes. Systematic reviews have highlighted the need for robust multicentre randomised controlled trials with longer term follow-up. METHODS: The study design is a randomised controlled study to explore the feasibility of providing earlier and enhanced rehabilitation to mechanically ventilated patients at high risk of ICU-acquired weakness within the ICU. The rehabilitation intervention involves a structured programme, with progression along a functionally based mobility protocol according to set safety criteria. The overall aim of the intervention is to commence mobilisation at an earlier time point in the patient's illness and increase mobility of the patient through their recovery trajectory. Participants will be randomised to enhanced rehabilitation or standard care, with the aim of recruiting at least 100 patients over 16 months. The trial design will assess recruitment and consent rates from eligible patients, compliance with the intervention, and assess a range of possible outcome measures for use in a definitive trial, with follow-up continuing for 12 months post hospital discharge. DISCUSSION: This study will evaluate the feasibility of providing an earlier and enhanced rehabilitation intervention to mechanically ventilated patients in critical care. We will identify strengths and weaknesses of the proposed protocol and the utility and characteristics of the outcome measures. The results from this study will inform the design of a phase III multicentre trial of enhanced rehabilitation for critically ill adults. TRIAL REGISTRATION: ISRCTN90103222, 13/08/2015; retrospectively registered.

The Association Between Visiting Intensivists and ICU Outcomes.

OBJECTIVES: We hypothesized that intensivists unfamiliar with an ICU team and the context of that ICU would affect patient outcomes. We examined differences in mortality when ICU patients were admitted under intensivists routinely working in that ICU and compared with those admitted by intensivists familiar with an ICU elsewhere in the same hospital. DESIGN, SETTINGS, AND PATIENTS: A 5-year natural experimental crossover study involving patients admitted to four ICUs in a large U.K. teaching hospital. INTERVENTIONS: During a period of service reconfiguration, intensivists routinely rostered to work in one ICU worked in another of the hospital's four ICUs. "Home" intensivists were those who continued to work in their usual ICU; "visitor" intensivists were those who delivered care in an unfamiliar ICU. Patient data were obtained from electronic patient records to provide analysis on sex, age, admission Sequential Organ Failure Assessment score, date and time of admission, and admission type (elective, transfer, or unplanned). MEASUREMENTS AND MAIN RESULTS: We analyzed 9,981 admissions to four separate ICUs over a 5-year period. In total, 34.5% of patients were admitted by intensivists working in nonfamiliar surroundings. Visitor intensivists admitted patients with similar age and gender distributions but with greater physiologic derangement (mean Sequential Organ Failure Assessment score, 4.1 ± 2.8 vs 3.9 ± 2.8; p < 0.001) than home intensivists. Overall ICU mortality rates were higher in visitor intensivists, albeit not significantly so (11.5% vs 10.2%; p = 0.052). However, when the ICUs were analyzed separately, visitor mortality rates were found to be significantly higher than for home intensivists in two of the four ICUs (p = 0.017, 0.006). A multivariable analysis adjusting for confounding factors and the clustering of consultants revealed that the overall mortality rate was significantly higher for visitors (odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.024). A significant interaction between the ICU and visitor status was also detected (p = 0.046), with the visitor effect remaining significant in the two ICUs identified previously (both p = 0.009). CONCLUSIONS: Visitor intensivists in some ICUs were associated with higher mortality. The reasons are unknown but could relate to intensivists' practices, unfamiliarity with the patients, or the interaction with the interprofessional team.

The Sara Combilizer® as an early mobilisation aid for critically ill patients: A prospective before and after study.

BACKGROUND: Early mobility within the ICU is associated with a number of positive outcomes including reductions in ICU and hospital length of stay and better functional recovery. The exact definition of 'early' mobility is still not defined, with the actual ability to mobilise limited by a number of perceived factors. The Sara Combilizer® is a combined tilt table and stretcher chair, which allows passive transfer of patients out of bed. This study aimed to assess whether the introduction of the Sara Combilizer® reduced time taken to first mobilise for patients mechanically ventilated for at least five days and at risk of ICU acquired weakness. METHODS: Patients admitted to a large UK critical care unit during the trial period and ventilated for ≥5days were included in the study. Baseline data was collected prospectively for a period of four months. The Sara Combilizer® was then introduced for a one month training and familiarisation period, followed by a further four months prospective data collection. The primary outcome was time to first mobilisation, defined as a Manchester Mobility Score ≥2. RESULTS: Following the introduction of the Sara Combilizer®, time taken to mobilise reduced significantly from 13.6 to 10.6days (p=0.028). SOFA scores were significantly higher at the point of first mobilisation in the Combilizer group (mean: 2.9±0.5 vs. 5.1±2.4; p=0.005). There was no statistical difference in therapy time between the groups, or ICU or hospital length of stay. CONCLUSIONS: The introduction of the Sara Combilizer® was associated with a significant reduction in time to mobilise patients ventilated for ≥5days, and patients were mobilised with a higher degree of organ failure. This was achieved without any increase in therapy time. The Sara Combilizer® may be a useful adjunct to an early mobility protocol within the ICU.

Systematic review of statins in sepsis: There is no evidence of dose response.

OBJECTIVES: Sepsis is a common cause of morbidity and mortality and is associated with significant costs to the healthcare organizations. We performed a systematic review and meta-analysis to assess whether high or low-dose statin therapy improved mortality in patients with sepsis. METHODS: The trials analyzed in this study were multicenter or single center randomized control studies using statins for sepsis in a hospital setting. The patients included were adults with suspected or confirmed infection. INTERVENTIONS: This study found eight randomized controlled trials where participants were given either a statin or placebo daily for 14-28 days, the duration of their illness, or until their death or discharge, which ever occurred first. PRIMARY AND SECONDARY OUTCOMES MEASURED: This meta-analysis measured the effect of statin therapy on in hospital and 28 days mortality. RESULTS: In unselected patients, there was no demonstrable difference in the 28 days mortality (relative risk [RR] 0.88 95% confidence interval [CI], 0.70-1.12 and P = 0.16). There was also no significant difference between statin versus placebo for in-hospital mortality (RR 0.98 95% CI, 0.85-1.14 P = 0.36). When the studies where divided into low-dose and high-dose groups, there were no statistically significant differences for in-hospital mortality between low-dose statin versus placebo for (RR 0.81 CI 0.44-1.49 P = 0.27) or high-dose statin versus placebo (RR 0.99 95% CI 0.85-1.16, P = 0.28). There was no significant difference in adverse effects between the high- and low-dose groups. CONCLUSIONS: In this meta-analysis, we found that the use of statins did not significantly improve either in-hospital mortality or 28-day mortality in patients with sepsis. In the low-dose group, there were fewer quality multicenter studies; hence, conclusions based on the results of this subgroup are limited.

Tracheostomy in special groups of critically ill patients: Who, when, and where?

Tracheostomy is one of the most common procedures undertaken in critically ill patients. It offers many theoretical advantages over translaryngeal intubation. Recent evidence in a heterogeneous group of critically ill patients, however, has not demonstrated a benefit for tracheostomy, in terms of mortality, length of stay in Intensive Care Unit (ICU), or incidence of ventilator-associated pneumonia. It may be a beneficial intervention in articular subsets of ICU patients. In this article, we will focus on the evidence for the timing of tracheostomy and its effect on various subgroups of patients in critical care.