Background:We performed a systematic review with meta-analysis to examine the relationship between sedation including a continuous IV opioid infusion and duration of mechanical ventilation (MV) and relevant secondary outcomes in MV critically ill adults. Methods:We searched MEDLINE, EMBASE, and Cochrane CENTRAL database up to March 2025. We included randomized controlled trials in MV critically ill adults comparing use of sedation including a continuous IV opioid versus sedation without. We assessed MV duration, pain, delirium and coma occurrence, ICU/hospital length of stay (LOS) and 28-day mortality. Study risk of bias was evaluated (PROSPERO: CRD42024498555). We pooled data using a Restricted Maximum Likelihood Estimation random-effects model and followed PRISMA guidelines. Results:Eight studies (n = 803 patients) published between 2006 and 2021 were included. Sedation including a continuous IV opioid (vs. sedation without) may increase MV duration (3 studies, 425 patients, mean difference (MD) = 3.63 h, 95% confidence interval (CI) 2.27-4.99, very low certainty), reduce pain (2 studies, VAS score at 24 h MD = -0.44 mm, 95% CI - 0.82 to -0.07, low certainty), reduce delirium (3 studies, odds ratio (OR) = 0.28, 95% CI 0.16 to 0.47, very low certainty) and reduce mortality (3 studies, OR = 0.41, 95% CI 0.21 to 0.80, very low certainty). Sedation including a continuous IV opioid does not increase coma or reduce ICU/ hospital LOS. Risk of bias was critical for most studies. Conclusion:The effect of sedation including a continuous IV opioid on MV duration, pain delirium, coma, mortality and LOS remain uncertain. The role for continuous IV opioids as a part of ICU sedation regimens requires additional evaluation.

Background:Eye movement desensitisation and reprocessing (EMDR) is a guideline-recommended treatment for post-traumatic stress disorder (PTSD), but evidence in survivors of critical illness remains limited. We assessed the feasibility, acceptability, and safety of EMDR for critical care survivors with clinically significant post-traumatic stress symptoms, and generated exploratory clinical outcome estimates to inform a future definitive trial. Methods:We conducted a mixed-methods, randomised, single-blind, parallel group-controlled, feasibility trial at three UK National Health Service hospitals. Adults (≥18 years) with an intensive care stay >24 h were approached before hospital discharge and followed within an observational cohort. At 2-3 months, participants were screened for post-traumatic stress symptoms (Impact of Event Scale-Revised); those scoring ≥22 were invited and randomly assigned (1:1) to EMDR plus treatment as usual (TAU) or TAU. EMDR comprised up to 16 sessions delivered face-to-face or online by accredited therapists. Primary outcomes were feasibility (recruitment, retention, intervention uptake, fidelity) and safety. Symptoms were assessed using Clinician-administered PTSD Scale for Diagnostic and Statistical Manual-5 (CAPS-5) at 3 and 12 months. Analyses followed intention-to-treat principles. The trial was registered on ClinicalTrials.gov (NCT05591625) and is closed to recruitment. Findings:Between Feb 20, 2023, and May 13, 2024, 160 patients were recruited to the observational cohort; 40 were randomised, with 20 allocated to EMDR plus TAU and 20 to TAU. Median age was 59.5 years (IQR 52.0-66.0); 21 participants (53%) were female and 19 (48%) were male. At 12 months, 39 (98%, 95% CI 86.8-99.9) of 40 randomised participants completed CAPS-5 follow-up. In the EMDR plus TAU group, 18 (90%, 95% CI 68.3-98.8) of 20 participants initiated treatment; mean sessions attended was 10.4 (SD 7.0), and 15 (75%) of 20 completed a full therapeutic course. Mean CAPS-5 score change was -15.6 (SD 12.5) in the EMDR plus TAU group and -1.6 (SD 11.8) in the TAU group, giving an exploratory unadjusted between-group difference of -14.1 points (95% CI -22.0 to -6.2). No treatment-related serious adverse events were identified. Interpretation:A staged trial pathway of symptom screening, clinician-rated PTSD assessment, randomisation, and EMDR delivery was feasible and broadly acceptable in survivors of critical illness with clinically significant post-traumatic stress symptoms. Exploratory clinician-rated PTSD outcome estimates were hypothesis-generating and support progression to a definitive multicentre trial, but should not be interpreted as evidence of treatment effectiveness. Funding:Andrew Bates was funded by National Institute for Health and Care Research Clinical Doctoral Research fellowship (grant number: NIHR302160).

Airway mucus is a highly specialised secretory fluid which functions as a physical and immunological barrier to pathogens whilst lubricating the airways and humifying atmospheric air. Dysfunction is common during critical illness and is characterised by changes in production rate, chemical composition, physical properties, and inflammatory phenotype. Mucociliary clearance, which is determined in part by mucus characteristics and in part by ciliary function, is also dysfunctional in critical illness via disease related and iatrogenic mechanisms. The consequences of mucus dysfunction are potentially devastating, contributing to prolonged ventilator dependency, increased risk of secondary pneumonia, and worsened lung injury. Mucolytic therapies are designed to decrease viscosity, improve expectoration/suctioning, and thereby promote mucus removal. Mucolytics, including hypertonic saline, dornase alfa/rhDNase, nebulised heparin, carbocisteine/N-Acetyl cysteine, are commonly used in critically ill patients. This review summarises the physiology and pathophysiology of mucus and the existing evidence for the use of mucolytics in critically ill patients and speculates on journey to individualised mucolytic therapy.

Mammalian cell membranes composed of a mixture of glycerophospholipids, the relative composition of individual phospholipids and the dynamic flux vary between cells. In addition to their structural role, membrane phospholipids are involved in cellular signalling and immunomodulatory functions. In this study, we investigate the molecular membrane composition and dynamic flux of phosphatidylcholines in CD15+ leucocytes and CD3+ lymphocytes extracted from patients with acute respiratory distress syndrome (ARDS). We identified compositional variations between these cell types, where CD15+ cells had relatively higher quantities of alkyl-acyl PC species and CD3+ cells contained more arachidonoyl-PC species. There was a significant loss of arachidonoyl-PC in CD3+ cells in ARDS patients. Moreover, there were significant changes in PC composition and the methyl-D9 enrichment of individual molecular species in CD15+ cells from ARDS patients. This is the first study to perform an in vivo assessment of membrane composition and dynamic changes in immunological cells from ARDS patients.

Background: Mechanical ventilation is a common and often lifesaving intervention that is utilised in intensive care. However, the practices can vary between centres. Through this national survey we aim to gain more information about different strategies adopted across the UK.Methods: All adult intensive care units in the UK were approached to participate. The questionnaire was developed with an electronic survey engine and conducted between 09/11/2023 and 01/04/2024 (Survey Monkey (R)). The survey included questions on ventilator modes, settings, protocols/pathways, rescue strategies, immediate post-extubation period and follow-up.Results: There were 196 responses from 104 hospitals. The most widely adopted start-up ventilation mode was pressure-regulated volume-controlled mode. For acute hypoxaemic respiratory failure (AHRF), most of respondents reported full (39.8%) or partial compliance (58.1%) with the ARDSnet protocol, with PEEP settings being the commonest deviation. Prone positioning (99.0%), followed by recruitment manoeuvres (91.3%) were commonly used rescue measures during AHRF. APRV (55.7%), inhaled (51.3%) and systemic pulmonary vasodilators (44.1%) were also commonly used. Conservative oxygen targets (SaO2 of 88%-92%) were commonly adopted (70.6%). As a care bundle, intermittent ETT cuff pressure monitoring was more common (65.5%) than continuous cuff pressure monitoring (20.0%). Propofol and alfentanil were the most common initial sedative and analgesia (99.5% and 56.9%) respectively. Routine volatile anaesthetic use was rare.Conclusions: Our survey has shown significant variation of practice in common but crucial elements of management of patients receiving mechanical ventilation. We hope the results in our survey highlight potential future areas of research.Collaborators South-coast Peri-operative Audit and Research Collaborative (SPARC) Severn Trainee Anaesthetic and Critical Care Research group (STAR) Collaborative research in Anaesthesia in the Northeast (CRANE)Collaborators South-coast Peri-operative Audit and Research Collaborative (SPARC) Severn Trainee Anaesthetic and Critical Care Research group (STAR) Collaborative research in Anaesthesia in the Northeast (CRANE)Collaborators South-coast Peri-operative Audit and Research Collaborative (SPARC) Severn Trainee Anaesthetic and Critical Care Research group (STAR) Collaborative research in Anaesthesia in the Northeast (CRANE)

IntroductionPost-traumatic symptoms are common among patients discharged from intensive care units (ICUs), adversely affecting well-being, increasing healthcare utilisation and delaying return to work. Non-pharmacological approaches (eg, music, therapeutic touch and patient diaries) have been suggested as candidate interventions and trauma-focused psychological interventions have been endorsed by international bodies. Neither category of intervention is supported by definitive evidence of long-term clinical effectiveness in patients who have been critically ill. This study assesses the feasibility and acceptability of using eye-movement desensitisation and reprocessing (EMDR) to improve the mental health of ICU survivors.Methods and analysisEMERALD is a multicentre, two-part consent, pilot feasibility study, recruiting discharged ICU survivors from three hospitals in the UK. We are gathering demographics and measuring post-traumatic symptoms, anxiety, depression and quality of life at baseline. Two months after discharge, participants are screened for symptoms of post-traumatic stress disorder (PTSD) using the Impact of Events Scale-Revised (IES-R). Patients with IES-R scores<22 continue in an observation arm for 12 month follow-up. IES-R scores≥22 indicate above-threshold PTSD symptoms and trigger invitation to consent for part B: a randomised controlled trial (RCT) of EMDR versus usual care, with 1:1 randomisation. The study assesses feasibility (recruitment, retention and intervention fidelity) and acceptability (through semistructured interviews), using a theoretical acceptability framework. Clinical outcomes (PTSD, anxiety, depression and quality of life) are collected at baseline, 2 and 12 months, informing power calculations for a definitive RCT, with quantitative and qualitative data convergence guiding RCT refinements.Ethics and disseminationThis study has undergone external expert peer review and is funded by the National Institute for Health and Care Research (grant number: NIHR302160). Ethical approval has been granted by South Central-Hampshire A Research Ethics Committee (IRAS number: 317291). Results will be disseminated through the lay media, social media, peer-reviewed publication and conference presentation.Trial registration numberNCT05591625.

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of eye movement desensitisation and reprocessing (EMDR), a psychological intervention programme, on symptoms related to traumatic stress in survivors of life-threatening medical events. SECONDARY OBJECTIVES:to evaluate whether the effects of EMDR differ according to the nature of the medical event (associated diagnosis or setting), measured outcome (post-traumatic stress disorder (PTSD), anxiety, depression, or quality of life), or intervention (online, face-to-face, group or individual sessions).

Background: Approximately 50% of intensive care survivors experience persistent psychological symptoms. Eye-movement desensitisation and reprocessing (EMDR) is a widely recommended trauma-focussed psychological therapy, which has not been investigated systematically in a cohort of intensive care survivors: We therefore conducted a randomised pilot feasibility study of EMDR, using the Recent Traumatic Episode Protocol (R-TEP), to prevent psychological distress in intensive care survivors. Findings will determine whether it would be possible to conduct a fully-powered clinical effectiveness trial and inform trial design. Method: We aimed to recruit 26 patients who had been admitted to intensive care for over 24 h with COVID-19 infection. Consenting participants were randomised (1:1) to receive either usual care plus remotely delivered EMDR R-TEP or usual care alone (controls). The primary outcome was feasibility. We also report factors related to safety and symptom changes in post-traumatic stress disorder, (PTSD) anxiety and depression. Results: We approached 51 eligible patients, with 26 (51%) providing consent. Intervention adherence (sessions offered/sessions completed) was 83%, and 23/26 participants completed all study procedures. There were no attributable adverse events. Between baseline and 6-month follow-up, mean change in PTSD score was −8 (SD = 10.5) in the intervention group versus +0.75 (SD = 15.2) in controls (p = 0.126). There were no significant changes to anxiety or depression. Conclusion: Remotely delivered EMDR R-TEP met pre-determined feasibility and safety objectives. Whilst we achieved group separation in PTSD symptom change, we have identified a number of protocol refinements that would improve the design of a fully powered, multi-centre randomised controlled trial, consistent with currently recommended rehabilitation clinical pathways. Trial registration: ClinicalTrials.gov: NCT04455360.

Acute hypoxic respiratory failure (AHRF) is a prominent feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) critical illness. The severity of gas exchange impairment correlates with worse prognosis, and AHRF requiring mechanical ventilation is associated with substantial mortality. Persistent impaired gas exchange leading to hypoxemia often warrants the prolonged administration of a high fraction of inspired oxygen (FiO2). In SARS-CoV-2 AHRF, systemic vasculopathy with lung microthrombosis and microangiopathy further exacerbates poor gas exchange due to alveolar inflammation and oedema. Capillary congestion with microthrombosis is a common autopsy finding in the lungs of patients who die with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome. The need for a high FiO2 to normalise arterial hypoxemia and tissue hypoxia can result in alveolar hyperoxia. This in turn can lead to local alveolar oxidative stress with associated inflammation, alveolar epithelial cell apoptosis, surfactant dysfunction, pulmonary vascular abnormalities, resorption atelectasis, and impairment of innate immunity predisposing to secondary bacterial infections. While oxygen is a life-saving treatment, alveolar hyperoxia may exacerbate pre-existing lung injury. In this review, we provide a summary of oxygen toxicity mechanisms, evaluating the consequences of alveolar hyperoxia in COVID-19 and propose established and potential exploratory treatment pathways to minimise alveolar hyperoxia.

Introduction Physical rehabilitation delivered early following admission to the intensive care unit (ICU) has the potential to improve short-term and long-term outcomes. The use of supine cycling together with other rehabilitation techniques has potential as a method of introducing rehabilitation earlier in the patient journey. The aim of the study is to determine the feasibility of delivering the designed protocol of a randomised clinical trial comparing a protocolised early rehabilitation programme including cycling with usual care. This feasibility study will inform a larger multicentre study. Methods and analysis 90 acute care medical patients from two mixed medical-surgical ICUs will be recruited. We will include ventilated patients within 72 hours of initiation of mechanical ventilation and expected to be ventilated a further 48 hours or more. Patients will receive usual care or usual care plus two 30 min rehabilitation sessions 5days/week. Feasibility outcomes are (1) recruitment of one to two patients per month per site; (2) protocol fidelity with >75% of patients commencing interventions within 72 hours of mechanical ventilation, with >70% interventions delivered; and (3) blinded outcome measures recorded at three time points in >80% of patients. Secondary outcomes are (1) strength and function, the Physical Function ICU Test-scored measured on ICU discharge; (2) hospital length of stay; and (3) mental health and physical ability at 3 months using the WHO Disability Assessment Schedule 2. An economic analysis using hospital health services data reported with an embedded health economic study will collect and assess economic and quality of life data including the Hospital Anxiety and Depression Scales core, the Eurogol-5 Dimension-5 Level and the Impact of Event Score. Ethics and dissemination The study has ethical approval from the South Central Hampshire A Research Ethics Committee (19/SC/0016). All amendments will be approved by this committee. An independent trial monitoring committee is overseeing the study. Results will be made available to critical care survivors, their caregivers, the critical care societies and other researchers.

AbstractSince the declaration of the novel SARS‐CoV‐2 virus pandemic, health systems/ health‐care‐workers globally have been overwhelmed by a vast number of COVID‐19 related hospitalizations and intensive care unit (ICU) admissions. During the early stages of the pandemic, the lack of formalized evidence‐based guidelines in all aspects of patient management was a significant challenge. Coupled with a lack of effective pharmacotherapies resulted in unsatisfactory outcomes in ICU patients. The anticipated increment in ICU surge capacity was staggering, with almost every ICU worldwide being advised to increase their capacity to allow adequate care provision in response to multiple waves of the pandemic. This increase in surge capacity required advanced planning and reassessments at every stage, taking advantage of experienced gained in combination with emerging evidence. In University Hospital Southampton General Intensive Care Unit (GICU), despite the initial lack of national and international guidance, we enhanced our ICU capacity and developed local guidance on all aspects of care to address the rapid demand from the increasing COVID‐19 admissions. The main element of this success was a multidisciplinary team approach intertwined with equipment and infrastructural reorganization. This narrative review provides an insight into the approach adopted by our center to manage patients with COVID‐19 critical illness, exploring the initial planning process, including contingency preparations to accommodate (360% capacity increment) and adaptation of our management pathways as more evidence emerged throughout the pandemic to provide the most appropriate levels of care to our patients. We hope our experience will benefit other intensive care units worldwide.This article is categorized under: Infectious Diseases > Genetics/Genomics/Epigenetics

BACKGROUND:Reports of significant psychological stress among frontline healthcare workers are emerging from the Covid-19 outbreak in China. Concerningly, these match findings from previous infective outbreaks, which resulted in long-term psychological pathology.METHODS:During the Covid-19 pandemic, a multi-disciplinary cohort of Intensive Care staff completed an online survey of psychological well-being and rated the perceived usefulness of supportive interventions.RESULTS:Sixty per cent of invited staff responded. Seventy-seven per cent reported normal/high level of resilience. Thirty-two staff (35%) reported anxiety of a level at which formal psychological assessment is recommended. Sixteen (14%) staff members reported symptomology suggestive of post-traumatic stress disorder (PTSD). Multiple regression analysis revealed a significant relationship between job-related well-being, anxiety (p = 0.003) and PTSD (p = 0.005). Nurses were seven times more likely than doctors to score higher anxiety (OR = 6.8; p = 0.01). Preferred supportive interventions were adequate personal protective equipment, rest facilities and regular breaks. In the subgroup with high anxiety, psychological support was perceived as significantly more useful, with significant reductions reported for rest facilities and PPE.DISCUSSION:We report concerning levels of anxiety and post-traumatic stress symptomology among intensive care staff during the Covid-19 crisis, significantly impacting job-related well-being. Nurses are disproportionately affected. Overall, physiologically protective supportive interventions were preferred by staff; however, staff with established anxiety desire professional psychological help. Our findings match reports from SARS 2003 and China 2019. To mitigate long-term psychological consequences of caring for patients during a pandemic, easily deliverable protective strategies should be instigated, supported by formal and longer-term psychological support. Particular attention should be paid to developing strategies which support nursing staff.

OBJECTIVES:To explore the experience of physical rehabilitation in the intensive care unit (ICU), from the perspective of patients and relatives. DESIGN:Exploratory, qualitative study. PARTICIPANTS:Five former ICU patients and five family members of former ICU patients recruited from ICU support groups across the UK. INTERVENTIONS:Semi-structured interviews. MAIN OUTCOME MEASURES:Participants' experiences of physical rehabilitation in the ICU. Data were analysed using an iterative thematic approach. RESULTS:Four main themes were identified: Trust and Rapport, Necessity (of treatment), Psychological Benefit, and Goal Setting: Whose goal is it anyway? Despite a lack of enjoyment, patients tend to comply with physical rehabilitation, due in part to a positive patient-therapist relationship. There was agreement across participants that physical rehabilitation should be started as soon as possible after admission to ICU and exhaustion was highlighted as the biggest challenge to participation. In addition to aiding physical recovery, physical rehabilitation in the ICU may also provide psychological support for both patients and relatives. Finally, participants described a desire for therapists to direct goal setting in the early stages of recovery as they felt unable to engage in the process due to other priorities. CONCLUSIONS:The experience of physical rehabilitation on ICU may be influenced by key aspects of person-centred care. This study suggests that patients and relatives are keen for physical rehabilitation to start as soon as possible, which is a crucial new finding to support the practice of early rehabilitation in the ICU.

BACKGROUND: ARDS is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS. The aim of this review is to assess the effects of immunonutrition on mechanically ventilated adults with ARDS compared to the standard feeding formula. METHODS: We searched MEDLINE, EMBASE, CENTRAL, conference proceedings, and trial registries for appropriate studies up to April 2018. We performed statistical analysis according to Cochrane methodological standards. We used the GRADE approach to assess the quality of evidence for each outcome. RESULTS: We identified 10 randomized controlled trials with 1,015 participants. All of the studies compared an enteral formula or additional supplemental omega-3 fatty acids (eg, eicosapentaenoic acid, docosahexaenoic acid), gamma-linolenic acid, and antioxidants. All of the studies reported mortality. For the primary outcome, there was no difference in all-cause mortality (for the longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids, gamma-linolenic acid, and antioxidants (risk ratio = 0.79, 95% CI 0.59-1.07; low-quality evidence). For the secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ICU length of stay, ventilator days, and oxygenation or increases harm. CONCLUSIONS: This Cochrane meta-analysis of 10 studies of varying quality examined the effects of omega-3 fatty acids and antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ventilator days, ICU length of stay, or oxygenation due to the very low quality of evidence.

Although the distribution of cellular membrane phospholipid composition is well characterised in human erythrocytes, in-vivo turnover and dynamic flux of phospholipids between plasma and erythrocytes in physiological and in particular during disease states are mostly unknown. Erythrocyte mass primarily consisted of lipids and phosphatidylcholine (PC) contributes to the significant proportion of phospholipid membrane composition. Esterified membrane PC can be utilised during pathological processes to generate pro and anti-inflammatory lipid mediators, which can contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, utilising isotope labelling of choline and analytical methods with electrospray mass spectrometry (ESI-MS/MS), we characterised individual molecular composition and dynamic exchange of PC, sphingomyelins (SM) and lysophosphatidylcholines (LPC) between plasma and erythrocytes. In ARDS patients, there were significant alterations in PC molecular composition, coupled with a continuous loss of arachidonoyl-PC species over time. Infusion of methyl-D9-choline chloride resulted in enrichment of labelled choline into plasma PC and LPC via CDP-choline pathway with subsequent incorporation into erythrocyte PC. As expected, erythrocyte methyl-D9 PC enrichment is much slower than plasma. Patients had much faster and higher fractional enrichment of all PC and LPC molecules suggesting increased flux between plasma and erythrocytes. There was a particular pattern of incorporation, where the arachidonoyl-PC species achieved equilibrium with plasma rapidly and retained highest concentrations of enrichment compared to the other PC species. Increased enrichment of arachidonoyl-PC coupled with virtually no increase or depletion of its concentrations suggests the possibility of substrate donation for other cell types for the participation of eicosanoid biosynthesis during inflammatory conditions like ARDS. In summary, this study revealed an alerted pattern erythrocyte molecular phospholipid composition and flux in patients with acute respiratory distress syndrome and the pathological consequences of these changes needs further exploration.

Background Acute respiratory distress syndrome (ARDS) is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Pharmacotherapies that moderate inflammation in ARDS are lacking. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS. Objectives To systematically review and critically appraise available evidence on the effects of immunonutrition compared to standard non-immunonutrition formula feeding on mechanically ventilated adults (aged 18 years or older) with acute respiratory distress syndrome (ARDS). Search methods We searched MEDLINE, Embase, CENTRAL, conference proceedings, and trial registries for appropriate studies up to 25 April 2018. We checked the references from published studies and reviews on this topic for potentially eligible studies. Selection criteria We included all randomized controlled trials (RCTs) and quasi-randomized controlled trials comparing immunonutrition versus a control or placebo nutritional formula in adults (aged 18 years or older) with ARDS, as defined by the Berlin definition of ARDS or, for older studies, by the American-European Consensus Criteria for both ARDS and acute lung injury. Data collection and analysis Two review authors independently assessed the quality of studies and extracted data from the included trials. We sought additional information from study authors. We performed statistical analysis according to Cochrane methodological standards. Our primary outcome was all-cause mortality. Secondary outcomes included intensive care unit (ICU) length of stay, ventilator days, indices of oxygenation, cardiac adverse events, gastrointestinal adverse events, and total number of adverse events. We used GRADE to assess the quality of evidence for each outcome. Main results We identified 10 randomized controlled trials with 1015 participants. All studies compared an enteral formula or additional supplemental omega-3 fatty acids (i.e. eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)), gamma-linolenic acid (GLA), and antioxidants. We assessed some of the included studies as having high risk of bias due to methodological shortcomings. Studies were heterogenous in nature and varied in several ways, including type and duration of interventions given, calorific targets, and reported outcomes. All studies reported mortality. For the primary outcome, study authors reported no differences in all-cause mortality (longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids and antioxidants (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07; participants = 1015; studies = 10; low-quality evidence).For secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants reduces ICU length of stay (mean difference (MD) -3.09 days. 95% CI -5.19 to -0.99; participants = 639; studies = 8; very low-quality evidence) and ventilator days (MD -2.24 days, 95% CI -3.77 to -0.71; participants = 581; studies = 7; very low-quality evidence). We are also uncertain whether omega-3 fatty acids and antioxidants improve oxygenation, defined as ratio of partial pressure of arterial oxygen (PaO₂) to fraction of inspired oxygen (FiO₂), at day 4 (MD 39 mmHg, 95% CI 10.75 to 67.02; participants = 676; studies = 8), or whether they increase adverse events such as cardiac events (RR 0.87, 95% CI 0.09 to 8.46; participants = 339; studies = 3; very low-quality evidence), gastrointestinal events (RR 1.11, 95% CI 0.71 to 1.75; participants = 427; studies = 4; very low-quality evidence), or total adverse events (RR 0.91, 95% CI 0.67 to 1.23; participants = 517; studies = 5; very low-quality evidence). Authors' conclusions This meta-analysis of 10 studies of varying quality examined effects of omega-3 fatty acids and/or antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves the duration of ventilator days and ICU length of stay or oxygenation at day 4 due to the very low quality of evidence. Adverse events associated with immunonutrition are also uncertain, as confidence intervals include the potential for increased cardiac, gastrointestinal, and total adverse events.

Acute respiratory distress syndrome (ARDS) is associated with a severe pro-inflammatory response; although decreased plasma cholesterol concentration has been linked to systemic inflammation, any association of phospholipid metabolic pathways with ARDS has not been characterized. Plasma phosphatidylcholine (PC), the major phospholipid of circulating lipoproteins, is synthesized in human liver by two biologically diverse pathways: the cytidine diphosphocholine (CDP):choline and phosphatidylethanolamine N-methyltransferase (PEMT) pathways. Here, we used ESI-MS/MS both to characterize plasma PC compositions and to quantify metabolic fluxes of both pathways using stable isotopes in patients with severe ARDS and in healthy controls. Direct incorporation of methyl-D9-choline estimated CDP:choline pathway flux, while PEMT flux was determined from incorporations of one and two methyl-D3 groups derived from methyl-D9-choline. The results of MS/MS analysis showed significant alterations in plasma PC composition in patients with ARDS versus healthy controls. In particular, the increased overall methyl-D9-PC enrichment and, most importantly, the much lower methyl-D3-PC and methyl-D6-PC enrichments suggest increased flux through the CDP:choline pathway and reduced flux through the PEMT pathway in ARDS. To our knowledge, this study is the first to demonstrate significant plasma PC molecular compositional changes combined with associated alterations in the dynamics of PC synthetic pathways in patients with ARDS.

Exposure to the microgravity environment induces physiological changes in the cardiovascular, musculoskeletal and sensorimotor systems in healthy astronauts. As space agencies prepare for extended duration missions, it is difficult to predict the extent of the effects that prolonged exposure to microgravity will have on astronauts. Prolonged bed rest is a model used by space agencies to simulate the effects of spaceflight on the human body, and bed rest studies have provided some insights into the effects of immobilisation and inactivity. Whilst microgravity exposure is confined to a relatively small population, on return to Earth, the physiological changes seen in astronauts parallel many changes routinely seen by physiotherapists on Earth in people with low back pain (LBP), muscle wasting diseases, exposure to prolonged bed rest, elite athletes and critically ill patients in intensive care. The medical operations team at the European Space Agency are currently involved in preparing astronauts for spaceflight, advising on exercises whilst astronauts are on the International Space Station, and reconditioning astronauts following their return. There are a number of parallels between this role and contemporary roles performed by physiotherapists working with elite athletes and muscle wasting conditions. This clinical commentary will draw parallels between changes which occur to the neuromuscular system in the absence of gravity and conditions which occur on Earth. Implications for physiotherapy management of astronauts and terrestrial patients will be discussed.

Early mobilisation initiatives within the critical care environment have been shown to improve outcomes for patients. Early mobilisation has been defined as occurring within the first two to five days of the intensive care stay, but in practice this can be difficult to deliver. We conducted a quality improvement (QI) project to deliver early mobilisation in a large general intensive care unit. Mechanically ventilated medical patients received an integrated package of care involving two additional daily sessions of mobility therapy, in combination with minimal sedation where possible. Prospective baseline data was collected from January to March 2012; the QI project commenced in April 2012. Improvement cycle 1 completed in March 2015 and improvement cycle 2 in March 2016. Results have suggested a reduction in time to first mobilisation for intensive care survivors from 16.3 days in 2012, to 4.3 days at the end of improvement cycle 2. This was associated with a decrease in mean intensive care length of stay from 20.8 days in 2012, to 11.2 days at the end of improvement cycle 2. This QI project enabled patients to mobilise out of bed within the first five days of their intensive care stay and to be discharged earlier from the ICU, on going analysis is required to verify these findings.