Imperial College London

ProfessorStephenBrett

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Critical Care
 
 
 
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Contact

 

+44 (0)20 3313 4521stephen.brett Website

 
 
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Location

 

Hammersmith House 570Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

224 results found

Barnacle JR, Cairney G, Rainsley J, Mercuri L, Gibani MM, Cooke GS, Brett SJet al., 2021, Changes in the hospital admission profile of COVID-19 positive patients at a central London trust., Journal of Infection, Vol: 82, Pages: 159-198, ISSN: 0163-4453

Journal article

Stephens J, Wong J, Broomhead R, Stumpfle R, Waheed U, Patel P, Brett S, Soni Set al., 2020, Raised serum amylase in COVID-19 patients may not be associated with pancreatitis, British Journal of Surgery, ISSN: 0007-1323

Journal article

Benger JR, Lazaroo MJ, Clout M, Voss S, Black S, Brett S, Kirby K, Nolan JP, Reeves BC, Robinson M, Scott LJ, Smartt H, South A, Taylor J, Thomas M, Wordsworth S, Rogers CAet al., 2020, Randomized trial of the i-gel supraglottic airway device versus tracheal intubation during out of hospital cardiac arrest (AIRWAYS-2): Patient outcomes at three and six months, Resuscitation, Vol: 157, Pages: 74-82, ISSN: 0300-9572

AimThe AIRWAYS-2 cluster randomised controlled trial compared the i-gel supraglottic airway device (SGA) with tracheal intubation (TI) as the first advanced airway management (AAM) strategy used by Emergency Medical Service clinicians (paramedics) treating adult patients with non-traumatic out-of-hospital cardiac arrest (OHCA). It showed no difference between the two groups in the primary outcome of modified Rankin Scale (mRS) score at 30 days/hospital discharge. This paper reports outcomes to 6 months.MethodsParamedics from four ambulance services in England were randomised 1:1 to use an i-gel SGA (759 paramedics) or TI (764 paramedics) as their initial approach to AAM. Adults who had a non-traumatic OHCA and were attended by a participating paramedic were enrolled automatically under a waiver of consent. Survivors were invited to complete questionnaires at three and six months after OHCA. Outcomes were analysed using regression methods.Results767/9296 (8.3%) enrolled patients survived to 30 days/hospital discharge and 317/767 survivors (41.3%) consented and were followed-up to six months. No significant differences were found between the two treatment groups in the primary outcome measure (mRS score: 3 months: odds ratio (OR) for good recovery (i-gel/TI, OR) 0.89, 95% CI 0.69–1.14; 6 months OR 0.91, 95% CI 0.71–1.16). EQ-5D-5L scores were also similar between groups and sensitivity analyses did not alter the findings.ConclusionThere were no statistically significant differences between the TI and i-gel groups at three and six months. We therefore conclude that the initially reported finding of no significant difference between groups at 30 days/hospital discharge was sustained when the period of follow-up was extended to six months.

Journal article

Gasparini M, Khan S, Patel JM, Parekh D, Bangash MN, Stumpfle R, Shah A, Baharlo B, Soni Set al., 2020, Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID-19: a multicentre observational study, ANAESTHESIA, ISSN: 0003-2409

Journal article

Labeau SO, Afonso E, Benbenishty J, Blackwood B, Boulanger C, Brett SJ, Calvino-Gunther S, Chaboyer W, Coyer F, Deschepper M, Francois G, Honore PM, Jankovic R, Khanna AK, Llaurado-Serra M, Lin F, Rose L, Rubulotta F, Saager L, Williams G, Blot Set al., 2020, Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study, INTENSIVE CARE MEDICINE, ISSN: 0342-4642

Journal article

Gross J, Borkowski J, Brett S, 2020, Patient or family perceived deterioration in functional status and outcome after Intensive Care admission: a retrospective cohort analysis of routinely collected data, BMJ Open, Vol: 10, Pages: 1-6, ISSN: 2044-6055

Objective: To explore the association of patient or family reported functional deterioration (defined by a single question) in the preceding year, with mortality outcome for those admitted to the Intensive Care Unit (ICU).Design: Retrospective observational analysis of a routinely collected data source.Participants: Patients that were admitted to the ICU at Northwick Park and St Marks Hospitals, London North West University Healthcare NHS Trust between 1/10/2017 to 15/6/2019 were included. Patients were excluded if they had a prior ICU admission during the existing hospital episode or if information on functional deterioration could not be retrieved from either the patient or their advocate.Primary Outcomes: Mortality at the point of hospital discharge and 1 year following admission to the ICU.Results: Of the 1006 patients who were admitted to the ICU during the study period, information on functional deterioration was available for 621 patients who were included in the analysis. From these, 251 (40.4%) patients had patient or family reported functional deterioration in the preceding year, whilst 370 (59.6%) patients had a perceived stable functional baseline. Comparing the two groups, mortality was significantly higher in those who had functionally deteriorated compared to those with stable baseline function, at the point of hospital discharge (45.4% versus 25.9%; P<0.0001) and at 1 year (59.4% versus 33.0%; P<0.0001). Conclusion: Patient or family reported functional deterioration was significantly associated with higher mortality at the point of hospital discharge and at 1 year. The concept of functional deterioration in the lead up to ICU admission warrants further exploration.

Journal article

Stephens JR, Stümpfle R, Patel P, Brett SJ, Broomhead R, Baharlo B, Soni Set al., 2020, Analysis of critical care severity of illness scoring systems in patients with coronavirus disease 2019: a retrospective analysis of three U.K. ICUs., Critical Care Medicine, Vol: 49, Pages: e105-e107, ISSN: 0090-3493

Journal article

Reader T, Dayal R, Brett S, 2020, At the end: a vignette-based investigation of strategies for managing end-of-life decisions in the Intensive Care Unit, Journal of the Intensive Care Society, ISSN: 1751-1437

Background. Decision-making on End-of-life (EOL) is an inevitable, yet highly complex, aspect of intensive care decision-making. EOL decisions can be challenging both in terms of clinical judgement and social interaction with families, and these two process often become intertwined. This is especially apparent at times when clinicians are required to seek the views of surrogate decision makers (i.e., family members) when considering palliative care. Methods. Using a vignette-based interview methodology, we explored how interactions with family members influence EOL decisions by ICU clinicians (n=24), and identified strategies for reaching consensus with families during this highly emotional phase of ICU care. Results. We found that the enactment of EOL decisions were reported as being affected by a form of loss aversion, whereby concerns over the consequences of not reaching a consensus with families weighed heavily in the minds of clinicians. Fear of conflict with families tended to arise from anticipated unrealistic family expectations of care, family normalization of patient incapacity, and belief systems that prohibit end-of-life decision-making. Conclusions. To support decision makers in reaching consensus, various strategies for effective, coherent, and targeted communication (e.g., patient deterioration and limits of clinical treatment) were suggested as ways to effectively consult with families on EOL decision-making.

Journal article

Tran LN, Patel J, Yang J, ONeill C, Yin D, Nguyen R, Pogson D, Deakin C, Harris T, Brett S, Page V, Parnia Set al., 2020, The Association between post-cardiac arrest cerebral oxygenation and survival with favorable neurological outcomes: a multicenter study, Resuscitation, Vol: 154, Pages: 85-92, ISSN: 0300-9572

ObjectiveCerebral oximetry is a non-invasive system that uses near infrared spectroscopy to measure regional cerebral oxygenation (rSO2) in the frontal lobe of the brain. Post-cardiac arrest rSO2 may be associated with survival and neurological outcomes in out-of-hospital cardiac arrest patients; however, no studies have examined relationships between rSO2 and neurological outcomes following in-hospital cardiac arrest (IHCA). We tested the hypothesis that rSO2 following IHCA is associated with survival and favorable neurological outcomes.DesignProspective study from nine acute care hospital in the United States and United Kingdom.PatientsConvenience sample of IHCA patients admitted to the intensive care unit with post-cardiac arrest syndrome.InterventionsCerebral oximetry monitoring (Equanox 7600, Nonin Medical, MN, USA) during the first 48 hours after IHCA.Measurements and Main ResultsSubject’s rSO2 was calculated as the mean of collected data at different time intervals: hourly between 1-6 hour, 6-12 hr, 12-18hr, 18-24 hr and 24-48hr. Demographic data pertaining to possible confounding variables for rSO2 and primary outcome were collected. The primary outcome was survival with favorable neurological outcomes (cerebral performance scale [CPC] 1-2) vs severe neurological injury or death (CPC 3-5) at hospital discharge. Univariate and multivariate statistical analyses were performed to correlate cerebral oximetry values and other variables with the primary outcome. Among 87 studied patients, 26 (29.9%) achieved CPC1-2. A significant difference in mean rSO2 was observed during hours 1-2 after IHCA in CPC 1-2 vs CPC3-5 (73.08 vs. 66.59, p = 0.031) but not at other time intervals. There were no differences in age, Charlson comorbidity index, APACHE II scores, CPR duration, mean arterial pressure, PaO2, PaCO2, and hemoglobin levels between two groups.ConclusionsThere may be a significant physiological difference in rSO2 in

Journal article

Labeau S, Afonso E, Benbenishty J, Blackwood B, Boulanger C, Brett S, Calvino-Gunther S, Chaboyer W, Coyer F, Deschepper M, François G, Honore PM, Jankovic R, Khanna AK, Llaurado-Serra M, Lin F, Rose L, Rubulotta F, Saager L, Williams G, Blot SIet al., 2020, Prevalence, Associated Factors and Outcomes of Pressure Injuries in Adult Intensive Care Unit Patients: “DecubICUs”, an International Point-Prevalence Study and ESICM Trials Group Project, Intensive Care Medicine, ISSN: 0342-4642

Purpose: Intensive care unit (ICU) patients are particularly susceptible to developingpressure injuries. Epidemiologic data is however unavailable. We aimed to providean international picture of the extent of pressure injuries and factors associated withICU-acquired pressure injuries in adult ICU patients.Methods: International one-day point-prevalence study; follow-up for outcomeassessment until hospital discharge (maximum 12 weeks). Factors associated withICU-acquired pressure injury and hospital mortality were assessed by generalisedlinear mixed-effects regression analysis.Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6%(95% confidence interval [CI], 25.9–27.3). ICU-acquired prevalence was 16.2%(95%CI, 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factorsindependently associated with ICU-acquired pressure injuries were older age, malesex, being underweight, emergency surgery, higher Simplified Acute PhysiologyScore II, Braden score<19, ICU stay>3 days, comorbidities (chronic obstructivepulmonary disease, immunodeficiency), organ support (renal replacement,mechanical ventilation on ICU admission), and being in a low or lower-middle incomeeconomy. Gradually increasing associations with mortality were identified forincreasing severity of pressure injury: Stage I (odds ratio [OR], 1.5; 95%CI, 1.2–1.8),Stage II (OR, 1.6; 95%CI, 1.4–1.9), and Stage III or worse (OR, 2.8; 95%CI, 2.3–3.3).Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquiredpressure injuries are associated with mainly intrinsic factors, and mortality. Optimalcare standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safetythreat.

Journal article

Goodwin L, Samuel K, Schofield B, Voss S, Brett S, Couper K, Gould D, Harrison D, Lall R, Nolan J, Perkins G, Soar J, Thomas M, Benger Jet al., 2020, Airway management during in-hospital cardiac arrest (IHCA) in adults: UK national survey and interview study with anaesthetic and intensive care trainees, Journal of the Intensive Care Society, ISSN: 1751-1437

Background: The optimal airway management strategy for in-hospital cardiac arrest (IHCA) is unknown.Methods: An online survey and telephone interviews with anaesthetic and intensive care trainee doctors identified by the United Kingdom (UK) Research and Audit Federation of Trainees. Questions explored IHCA frequency, grade and specialty of those attending, proportion of patients receiving advanced airway management, airway strategies immediately available, and views on a randomised trial of airway management strategies during IHCA.Results: Completed surveys were received from 128 hospital sites (76% response rate). Adult IHCAs were attended by anaesthesia staff at 40 sites (31%), intensive care staff at 37 sites (29%), and a combination of specialties at 51 sites (40%). The majority (123/128, 96%) of respondents reported immediate access to both tracheal intubation (TI) and supraglottic airways (SGAs). A bag-mask technique was used ‘very frequently’ or ‘frequently’ during IHCA by 111/128 (87%) of respondents, followed by SGAs (101/128, 79%) and TI (69/128, 54%). The majority (60/100, 60%) of respondents estimated that ≤30% of IHCA patients undergo TI, while 34 (34%) estimated this to be between 31-70%. Most respondents (102/128, 80%) would be ‘likely’ or ‘very likely’ to recruit future patients to a trial of alternative airway management strategies during IHCA. Interview data identified several barriers and facilitators to conducting research on airway management in IHCA.Conclusions: There is variation in airway management strategies for adult IHCA across the UK. Most respondents would be willing to take part in a randomised trial of airway management during IHCA.

Journal article

Bauchmuller K, Manson J, Tattersall R, Brown M, McNamara C, Singer M, Brett Set al., 2020, Haemophagocytic lymphohistiocytosis in adult critical care, Journal of the Intensive Care Society, Vol: 21, Pages: 256-268, ISSN: 1751-1437

Haemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe immune dysregulation,characterised by extreme inflammation, fever, cytopaenias and organ dysfunction. HLH can betriggered by conditions such as infection, auto-immune disease and malignancy, amongst others.Both a familial and a secondary form have been described, the latter being increasinglyrecognised in adult patients with critical illness. HLH is difficult to diagnose, often underrecognised and carries a high mortality. Patients can present in a very similar fashion to sepsis andthe two syndromes can co-exist and overlap, yet HLH requires specific immunosuppressivetherapy. HLH should be actively excluded in patients with presumed sepsis who either lack a clearfocus of infection or who are not responding to energetic infection management. Elevated serumferritin is a key biomarker that may indicate the need for further investigations for HLH and canguide treatment. Early diagnosis and a multidisciplinary approach to HLH management may savelives.

Journal article

Tatham KC, McAuley DF, Borthwick M, Henderson N, Bashevoy G, Brett SJet al., 2020, The National Institute for Health Research Critical Care Research Priority Setting Survey 2018, Journal of the Intensive Care Society, Vol: 21, Pages: 198-201, ISSN: 1751-1437

IntroductionDefining research priorities in intensive care is key todetermining appropriate allocation of funding. Several topics were identified from the recent James Lind Alliance (JLA) priority setting exerciseconducted with the Intensive Care Society(1). The JLA process included significant (and vital) patient/public contribution, but as a result may have failedto identify potential early-stage translational research topics, which are more likely identified by medical/academic members of relevant specialist intensive care groups. Theobjectiveof the present project was to complement the JLA project by generating an updated list of research prioritiesby facilitatingacademic research input.MethodAsurveywas conducted by the National Institute forHealth Research(NIHR)to identify the key research priorities from Intensive Care clinicians, including allied health professionals and academics, along with any evolving themes arising from translational research. Feasibility of all identified topics were then discussedand allocated to themesby ajoint clinical academics/NIHR focus group. ResultsThe survey was completed by 94 intensive care clinicians(including subspecialists),academicsand allied healthprofessions. In total203researchquestionswere identified, with the top fivethemesfocusing on:appropriate case selection (e.g.who and when to treat; 24%), ventilation(7%), sepsis (6%), delirium (5%) and rehabilitation (5%). DiscussionUtilising a methodology distinct from thatemployed by the JLAprocess, from a broad spectrum of intensive care clinicians/scientists,enabled identification of a variety of priority research areas. These topics cannowinform not only the investigator-led researchagenda, but will alsobe considered in due course by the NIHR for potential future funding calls.

Journal article

ISARIC clinical characterisation group, 2020, Global outbreak research: harmony not hegemony., Lancet Infect Dis, Vol: 20, Pages: 770-772

Journal article

Leon-Villapalos C, Wells M, Brett S, 2020, An exploratory study of staff perceptions of shift safety in the critical care unit and routinely available data on workforce, patient and organisational factors, BMJ Open, Vol: 10, ISSN: 2044-6055

Objectives To explore bedside professional reported (BPR) perceptions of safety in intensive care staff and the relationships between BPR safety, staffing, patient and work environment characteristics.Design An exploratory study of self-recorded staff perceptions of shift safety and routinely collected data.Setting A large teaching hospital comprising 70 critical care beds.Participants All clinical staff working in adult critical care.Interventions Staff recorded whether their shift felt ‘safe, unsafe or very unsafe’ for 29 consecutive days. We explored these perceptions and relationships between them and routine data on staffing, patient and environmental characteristics.Outcome measures Relationships between BPR safety and staffing, patient and work environment characteristics.Results 2836 BPR scores were recorded over 29 consecutive days (response rate 57.7%). Perceptions of safety varied between staff, including within the same shift. There was no correlation between perceptions of safety and two measures of staffing: care hours per patient day (r=0.13 p=0.108) and Safecare Allocate (r=−0.19 p=0.013). We found a significant, positive relationship between perceptions of safety and the percentage of level 3 (most severely ill) patients (r=0.32, p=0.0001). There was a significant inverse relationship between perceptions of safety and the percentage of level 1 patients on a shift (r=−0.42, p<0.0001). Perceptions of safety correlated negatively with increased numbers of patients (r=−0.44, p=0.0006) and higher percentage of patients located side rooms (r=0.63, p<0.0001). We found a significant relationship between perceptions of safety and the percentage of staff with a specialist critical care course (r=0.42. p=0.0001).Conclusion Existing staffing models, which are primarily influenced by staff-to-patient ratios, may not be sensitive to patient need. Other factors may be important drivers of staff perceptions of safety and should b

Journal article

Patel PB, Brett S, O'Callaghan D, Anjum A, Cross M, Warwick J, Gordon ACet al., 2020, A randomized clinical trial of methylnaltrexone for the treatment of opioid induced constipation & gastrointestinal stasis in intensive care patients; results from the MOTION trial, Intensive Care Medicine, Vol: 46, Pages: 747-755, ISSN: 0342-4642

PurposeConstipation can be a significant problem in critically unwell patients, associated with detrimental outcomes. Opioids are thought to contribute to the mechanism of bowel dysfunction. We tested if methylnaltrexone, a pure peripheral mu-opioid receptor antagonist, could reverse opioid induced constipationMethodsThe MOTION trial is a multi-centre, double blind, randomised placebo controlled trial to investigate whether methylnaltrexone alleviatesopioid induced constipation (OIC) in critical care patients. Eligibility criteria included adult ICU patients who were mechanically ventilated, receiving opioids and were constipated (had not opened bowels for a minimum 48 hours) despite prior administration of regular laxatives as per local bowel management protocol. The primary outcome was time to significant rescue-free laxation. Secondary outcomes included gastric residual volume, tolerance of enteral feeds, requirement for rescue laxatives, requirement for prokinetics, average number of bowel movements per day,escalation of opioid dose due to antagonism/reversal of analgesia, incidence of ventilator-associated pneumonia, incidence of diarrhoea and Clostridium difficileinfection and finally 28 day, ICU and hospital mortality.ResultsA total of 84 patients were enrolled and randomized (41 to methylnaltrexone and 43 to placebo). The baseline demographic characteristics of the two groups were generally well balanced. There was no significant differencein time to rescue-free laxation between the groups (Hazard ratio 1.42, 95%CI 0.82-2.46, p=0.22). There were no significant differencesin the majority of secondary outcomes, particularly days 1-3. However, during days 4-28, there were fewer median number of bowel movements per day in the methylnaltrexone group, (p=0.01) and a greater incidence of diarrhoea in the placebo group (p=0.02). There was a marked difference in mortality between the groups, with ten deaths in the methylnaltrexone group and two in the placebo group

Journal article

Grailey K, Murray E, Billings J, Brett Set al., 2020, How do critical care staff respond to organisational challenge? A qualitative exploration into personality types and cognitive processing in critical care, PLoS One, Vol: 15, ISSN: 1932-6203

Critical care staff are frequently required to respond to stressful scenarios. The way staff counter organisational challenge may be influenced by their underlying personality type, preferred style of cognitive processing and previous clinical experience. Our objective was to explore the personality types of a sample of critical care workers, and the potential relationship of this with cognitive processing. This was achieved through a qualitative interview study in which participants were presented with difficult but realistic scenarios pertaining to staffing. Data on individual’s personality were captured using the ‘16 Personality Factor’ assessment, a tool that produces scores for 16 different elements of an individual’s personality. The existence of perfectionist and pragmatic cognitive processing styles were identified as one theme emerging from a prior analysis of these interview transcripts. We aimed to validate this, explore our ability to categorise individuals into groups based upon their cognitive processing. We identified that some individuals strongly tended to either a perfectionist or pragmatic style of cognitive processing for the majority of their decisions; however most adapted their style of processing according to the nature of the decision. Overall participants generally demonstrated average scores for all 16 personality factors tested. However, we observed that some factors tended to higher scores than others, indicating a pattern within the personalities of our sample cohort. Whilst a small sample size, our data suggests that individuals working within the same critical care environment may have clear differences in their approach to problem solving as a consequence of both their personality type and preferred style of cognitive processing. Thus there may be individuals within this environment who would benefit from increased support to minimise their risk of cognitive dissonance and stress in times of challenge.

Journal article

Wandrag L, Brett SJ, Frost GS, Bountziouka V, Hickson Met al., 2019, Exploration of muscle loss and metabolic state during prolonged critical illness: Implications for intervention?, PLOS ONE, Vol: 14, ISSN: 1932-6203

Journal article

Palmer E, Post B, Klapaukh R, Marra G, MacCallum NS, Brealey D, Ercole A, Jones A, Ashworth S, Watkinson P, Beale R, Brett SJ, Young JD, Black C, Rashan A, Martin D, Singer M, Harris Set al., 2019, The association between supra-physiologic arterial oxygen levels and mortality in critically ill patients: a multi-centre observational cohort study, American Journal of Respiratory and Critical Care Medicine, Vol: 200, Pages: 1373-1380, ISSN: 1073-449X

Rationale: There is conflicting evidence on harm related to exposure to supra-physiologic arterial oxygen tensions (hyperoxemia) in critically ill patients. Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to intensive care units (ICUs) in 5 UK University Hospitals. Methods: Retrospective cohort of ICU admissions between 31st January 2014 - 31st December 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative (CC-HIC). Multivariable logistic regression modelled death in ICU by exposure to hyperoxemia. Measurements: Subsets with oxygen exposure windows of 0-1, 0-3, 0-5 and 0-7 days were evaluated, capturing 19,515, 10,525, 6,360 and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mmHg) divided by the hours of potential exposure (24, 72, 120, or 168 hours). Main Results: An association was found between exposure to hyperoxemia and ICU mortality [odds ratios (95% compatibility intervals); 1.15 (0.95-1.38), p = 0.15; 1.35 (1.04-1.74), p = 0.02; 1.5 (1.07-2.13), p = 0.02; and 1.74 (1.11-2.72), p = 0.02 for exposure windows of 0-1, 0-3, 0-5 and 0-7 days’ duration, respectively. However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation. Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.

Journal article

Wandrag L, Brett SJ, Frost G, To M, Loubo E, Jackson N, Umpleby M, Bountziouka V, Hickson Met al., 2019, Leucine-enriched essential amino acid supplementation in mechanically ventilated trauma patients – a feasibility study, Trials, Vol: 20, ISSN: 1745-6215

Background: Critically ill patients lose up to 2% muscle mass per day. We assessed the feasibility of administering a leucine-enriched essential amino acid (L-EAA) supplement to mechanically ventilated trauma patients with the aim of assessing the effect on skeletal muscle mass and function. Methods: A randomised feasibility study was performed over 6 months in intensive care (ICU), patients received 5g L-EAA five times per day in addition to standard feed (L-EAA group) or standard feed only (control group) up to 14 days. CRP, albumin, IL-6, IL-10, urinary 3-MH, nitrogen balance, protein turnover ([1-13C] leucine infusion), muscle depth change (ultrasound), functional change (Katz & Barthel indices) and muscle strength Medical Research Council (MRC) sum score to assess ICU Acquired Weakness, were measured sequentially.Results: Eight patients (9.5% of screened patients) were recruited over 6 months. L-EAA doses were provided on 91/124 (73%) occasions. Inflammatory and urinary marker data were collected; serial muscle depth measurements were lacking due to short length of stay. Protein turnover studies were performed on five occasions. MRC-sum score could not be performed as patients were not able to respond to the screening questions. The Katz & Barthel indices did not change. L-EAA delivery was achievable, but meaningful functional and muscle mass outcome measures require careful consideration in the design of a future RCT. Conclusion: L-EAA was practical to provide, but we found significant barriers to recruitment and measurement of the chosen outcomes which would need to be addressed in the design of a future, large randomised controlled trial.

Journal article

Wong JLC, Romano M, Kerry L, Kwong J, Low W, Brett S, Clements A, Beis K, Frankel Get al., 2019, OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo, Nature Communications, Vol: 10, ISSN: 2041-1723

Carbapenem-resistance in Klebsiella pneumoniae (KP) sequence type ST258 is mediated by carbapenemases (e.g. KPC-2) and loss or modification of the major non-selective porins OmpK35 and OmpK36. However, the mechanism underpinning OmpK36-mediated resistance and consequences of these changes on pathogenicity remain unknown. By solving the crystal structure of a clinical ST258 OmpK36 variant we provide direct structural evidence of pore constriction, mediated by a di-amino acid (Gly115-Asp116) insertion into loop 3, restricting diffusion of both nutrients (e.g. lactose) and Carbapenems. In the presence of KPC-2 this results in a 16-fold increase in MIC to Meropenem. Additionally, the Gly-Asp insertion impairs bacterial growth in lactose-containing medium and confers a significant in vivo fitness cost in a murine model of ventilator-associated pneumonia. Our data suggest that the continuous selective pressure imposed by widespread Carbapenem utilisation in hospital settings drives the expansion of KP expressing Gly-Asp insertion mutants, despite an associated fitness cost.

Journal article

Omassoli J, Hill NE, Woods DR, Delves SK, Fallowfield JL, Brett SJ, Wilson D, Corbett RW, Allsopp AJ, Stacey MJet al., 2019, Variation in renal responses to exercise in the heat with progressive acclimatisation, Journal of Science and Medicine in Sport, Vol: 22, Pages: 1004-1009, ISSN: 1440-2440

ObjectivesTo investigate changes in renal status from exercise in the heat with acclimatisation and to evaluate surrogates markers of Acute Kidney Injury.DesignProspective observational cohort study.Methods20 male volunteers performed 60 min standardised exercise in the heat, at baseline and on four subsequent occasions during a 23-day acclimatisation regimen. Blood was sampled before and after exercise for serum creatinine, copeptin, interleukin-6, normetanephrine and cortisol. Fractional excretion of sodium was calculated for corresponding urine samples. Ratings of Perceived Exertion were reported every 5 min during exercise. Acute Kidney Injury was defined as serum creatinine rise ≥26.5 μmol L−1 or fall in estimated glomerular filtration rate >25%. Predictive values of each candidate marker for developing Acute Kidney Injury were determined by ROC analysis.ResultsFrom baseline to Day 23, serum creatinine did not vary at rest, but showed a significant (P < 0.05) reduction post-exercise (120 [102, 139] versus 102 [91, 112] μmol L−1). Acute Kidney Injury was common (26/100 exposures) and occurred most frequently in the unacclimatised state. Log-normalised fractional excretion of sodium showed a significant interaction (exercise by acclimatization day), with post-exercise values tending to rise with acclimatisation. Ratings of Perceived Exertion predicted AKI (AUC 0.76, 95% confidence interval 0.65–0.88), performing at least as well as biochemical markers.ConclusionsHeat acclimatization is associated with reduced markers of renal stress and AKI incidence, perhaps due to improved regional perfusion. Acclimatisation and monitoring Ratings of Perceived Exertion are practical, non-invasive measures that could help to reduce renal injury from exercise in the heat.

Journal article

Kemp HI, Laycock H, Costello A, Brett SJet al., 2019, Chronic pain in critical care survivors: a narrative review, British Journal of Anaesthesia, Vol: 123, Pages: e372-e384, ISSN: 1471-6771

Chronic pain is an important problem after critical care admission. Estimates of the prevalence of chronic pain in the year after discharge range from 14% to 77% depending on the type of cohort, the tool used to measure pain, and the time point when pain was assessed. The majority of data available come from studies using health-related quality of life tools, although some have included pain-specific tools. Nociceptive, neuropathic, and nociplastic pain can occur in critical care survivors, but limited information about the aetiology, body site, and temporal trajectory of pain is currently available. Older age, pre-existing pain, and medical co-morbidity have been associated with pain after critical care admission. No trials were identified of interventions to target chronic pain in survivors specifically. Larger studies, using pain-specific tools, over an extended follow-up period are required to confirm the prevalence, identify risk factors, explore any association between acute and chronic pain in this setting, determine the underlying pathological mechanisms, and inform the development of future analgesic interventions.

Journal article

Nagendran M, Russell JA, Brett S, Perkins GD, Hajjar L, Mason AJ, Ashby D, Gordon Aet al., 2019, Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials, Intensive Care Medicine, Vol: 45, Pages: 844-855, ISSN: 0342-4642

PurposeWe performed an individual patient data meta-analysis to investigate the possible benefits and harms of vasopressin therapy in adults with septic shock both overall and in pre-defined subgroups.MethodsOur pre-specified study protocol is published on PROSPERO, CRD42017071698. We identified randomised clinical trials up to January 2019 investigating vasopressin therapy versus any other vasoactive comparator in adults with septic shock. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed as well as one-stage regression models with single treatment covariate interactions for subgroup analyses.ResultsFour trials were included with a total of 1453 patients. For the primary outcomes, there was no effect of vasopressin on 28-day mortality [relative risk (RR) 0.98, 95% CI 0.86–1.12] or serious adverse events (RR 1.02, 95% CI 0.82–1.26). Vasopressin led to more digital ischaemia [absolute risk difference (ARD) 1.7%, 95% CI 0.3%–3.2%] but fewer arrhythmias (ARD − 2.8%, 95% CI − 0.2% to − 5.3%). Mesenteric ischaemia and acute coronary syndrome events were similar between groups. Vasopressin reduced the requirement for renal replacement therapy (RRT) (RR 0.86, 95% CI 0.74–0.99), but this finding was not robust to sensitivity analyses. There were no statistically significant interactions in the pre-defined subgroups (baseline kidney injury severity, baseline lactate, baseline norepinephrine requirement and time to study inclusion).ConclusionsVasopressin therapy in septic shock had no effect on 28-day mortality although the confidence intervals are wide. It appears safe but with a different side effect profile from norepinephrine. The finding on reduced RRT should be interpreted cautiously. Future trials should focus on long-term outcomes in select patient groups as well as incorporating cost effectiveness analyses regarding possible reduced RRT use.

Journal article

Peden CJ, Stephens T, Martin G, Kahan BC, Thomson A, Rivett K, Wells D, Richardson G, Kerry S, Bion J, Pearse RM, Enhanced Peri-Operative Care for High-risk patients EPOCH trial groupet al., 2019, Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial, Lancet, Vol: 393, Pages: 2213-2221, ISSN: 0140-6736

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both t

Journal article

Kotfis K, Wittebole X, Jaschinski U, Sole-Violan J, Kashyap R, Leone M, Nanchal R, Fontes LE, Sakr Y, Vincent J-L, Tomas E, Bibonge EA, Charra B, Faroudy M, Doedens L, Farina Z, Adler D, Balkema C, Kok A, Alaya S, Gharsallah H, Muzha D, Temelkov A, Georgiev G, Simeonov G, Tsaryanski G, Georgiev S, Seliman A, Vrankovic S, Vucicevic Z, Gornik I, Barsic B, Husedzinovic I, Pavlik P, Manak J, Kieslichova E, Turek R, Fischer M, Valkova R, Dadak L, Dostal P, Malaska J, Hajek R, Zidkova A, Lavicka P, Starkopf J, Kheladze Z, Chkhaidze M, Kaloiani V, Medve L, Sarkany A, Kremer I, Marjanek Z, Tamasi P, Krupnova I, Vanags I, Liguts V, Pilvinis V, Vosylius S, Kekstas G, Balciunas M, Kolbusz A, Kubler A, Mielczarek B, Mikaszewska-Sokolewicz M, Kotfis K, Tamowicz B, Sulkowski W, Smuszkiewicz P, Pihowicz A, Trejnowska E, Hagau N, Filipescu D, Droc G, Lupu M, Nica A, Stoica R, Tomescu D, Constantinescu D, Zbaganu GV, Slavcovici A, Bagin V, Belsky D, Palyutin S, Shlyapnikov S, Bikkulova D, Gritsan A, Natalia G, Makarenko E, Kokhno V, Tolkach A, Kokarev E, Belotserkovskiy B, Zolotukhin K, Kulabukhov V, Soskic L, Palibrk I, Jankovic R, Jovanovic B, Pandurovic M, Bumbasirevic V, Uljarevic B, Surbatovic M, Ladjevic N, Slobodianiuk G, Sobona V, Cikova A, Gebhardtova A, Jun C, Yunbo S, Dong U, Feng S, Duan M, Xu Y, Xue X, Gao T, Xing X, Zhao X, Li C, Gengxihua G, Tan H, Xu J, Jiang L, Tiehe Q, Bingyu Q, Shi Q, Lv Z, Zhang L, Jingtao L, Zhen Z, Wang Z, Wang T, Yuhong L, Zhai Q, Chen Y, Wang C, Jiang W, Ruilan W, Chen Y, Xiaobo H, Ge H, Yan T, Yuhui C, Zhang J, Jian-Hong F, Zhu H, Huo F, Wang Y, Li C, Zhuang M, Ma Z, Sun J, Liuqingyue L, Yang M, Meng J, Ma S, Kang Y, Yu L, Peng Q, Wei Y, Zhang W, Sun R, Yeung A, Wan W, Sin K, Lee K, Wijanti M, Widodo U, Samsirun H, Sugiman T, Wisudarti C, Maskoen T, Hata N, Kobe Y, Nishida O, Miyazaki D, Nunomiya S, Uchino S, Kitamura N, Yamashita K, Hashimoto S, Fukushima H, Adib NN, Tai L, Tony B, Bigornia R, Palo J, Chatterjee S, Tan B, Kong A, Goh S, Leeet al., 2019, A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit, JOURNAL OF CRITICAL CARE, Vol: 51, Pages: 122-132, ISSN: 0883-9441

Journal article

Grailey K, Bryden D, Brett S, 2019, The faculty of intensive care medicine workforce survey – What impacts on our working lives?, Journal of the Intensive Care Society, Vol: 20, Pages: 111-117, ISSN: 1751-1437

The Faculty of Intensive Care Medicine distributes an annual survey to its Consultants, allowing the evaluation of workforce profile, working patterns and the opportunity for analysis of key information on issues affecting these. We undertook an exploratory review of the data provided within the 2016 survey, with the aim of identifying themes within respondents stated career intentions and associated factors. Given the modest (36%) response rate, we are unable to draw conclusions with certainty, but there are indications within the data that the UK Intensive Care Medicine consultant body is facing significant stressors whilst at work, due to working patterns and limited resources. The data within the 2016 survey provide a base from which to develop future Faculty of Intensive Care Medicine workforce surveys that will extract data about the positive aspects of a career in intensive care medicine. The survey data provide a signal that there may be significant potentially modifiable stressors for intensive care doctors, and as such affords support for initiatives to improve job planning and sharing of implemented solutions, as well as a need to focus on workforce wellbeing as an important and necessary contributor to patient safety within intensive care medicine.

Journal article

Antcliffe D, Burnham K, Al-Beidh F, Santhakumaran S, Brett S, Hinds C, Ashby D, Knight J, Gordon ACet al., 2019, Transcriptomic signatures in sepsis and a differential response to steroids: from the VANISH randomized trial, American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 980-986, ISSN: 1073-449X

Rationale: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration but conflicting survival effects. Two transcriptomic sepsis response signatures (SRS) have been identified. SRS1 is relatively immunosuppressed whilst SRS2 is relatively immunocompetent. Objectives: We aimed to categorized patients based on SRS endotypes to determine if these profiles influenced response to either norepinephrine or vasopressin, or to corticosteroids in septic shock. Methods: A post-hoc analysis was performed of a double-blind randomized clinical trial in septic shock (VANISH). Patients were included within 6 hours of onset of shock and were randomized to receive norepinephrine or vasopressin followed by hydrocortisone or placebo. Genome-wide gene expression profiling was performed and SRS endotype was determined using a previously established model using seven discriminant genes. Measurements and Main Results: Samples were available from 176 patients, 83 SRS1 and 93 SRS2. There was no significant interaction between SRS group and vasopressor assignment (p=0·50). However, there was an interaction between assignment to hydrocortisone or placebo, and SRS endotype (p=0·02). Hydrocortisone use was associated with increased mortality in those with an SRS2 phenotype (OR 7·9, 95%CI 1·6-39·9). Conclusions: Transcriptomic profile at onset of septic shock was associated with response to corticosteroids. Those with the immuno-competent SRS2 endotype had significantly higher mortality when given corticosteroids compared to placebo. Clinical trial registration available at www.isrctn.com, ID ISRCTN20769191.

Journal article

Hutchinson M, Sohal M, Layton M, Sriskandan S, Brett S, Hill P, Youngstein TABet al., 2019, STEROID-FREE MANAGEMENT OF LIFE-THREATENING HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN THE CONTEXT OF SUSPECTED LYMPHOPROLIFERATIVE DISEASE AND INFECTION, Annual Conference of the British-Soceity-for-Rheumatology, Publisher: OXFORD UNIV PRESS, ISSN: 1462-0324

Conference paper

Kemp H, Laycock H, Costello A, Brett Set al., 2019, Chronic pain in critical care survivors, BJA: British Journal of Anaesthesia, ISSN: 1471-6771

Chronic pain is an important problem following critical care admission. Estimates of prevalence of chronic pain in the year following discharge range from 14-77% depending on the type of cohort, the tool used to measure pain and the time point when pain was assessed. The majority of data available comefrom studies using health-related quality of life tools,although some have included pain-specific tools. Nociceptive, neuropathic and nociplastic pain can occur in critical caresurvivors butlimited information about aetiology, body site and temporal trajectory of pain is currently available. Older age, pre-existing pain andmedicalco-morbidity have been associated with pain after critical careadmission. No trials were identified of interventions to target chronic pain in survivors specifically. Larger studies, using pain-specific tools, over an extended follow up period are required to confirm prevalence, identify risk factors, explore anyassociation between acute and chronic pain in this setting, determine underlying pathological mechanisms and inform the development of future analgesic interventions.

Journal article

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