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

217 results found

Reader T, Dayal R, Brett S, 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

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

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

Barnacle JR, Cairney G, Rainsley J, Mercuri L, Gibani MM, Cooke GS, Brett SJet al., 2020, Changes in the hospital admission profile of COVID-19 positive patients at a central London trust., J Infect

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., 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

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

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, 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

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., 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

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, MOSAIC Investigators, Moffatt MF, O'Garra A, Openshaw PJMet al., 2019, Author Correction: Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza., Nature Immunology, Vol: 20, Pages: 373-373, ISSN: 1529-2908

In the version of this article initially published, a source of funding was not included in the Acknowledgements section. That section should include the following: P.J.M.O. was supported by EU FP7 PREPARE project 602525. The error has been corrected in the HTML and PDF version of the article.

Journal article

Corner EJ, Murray EJ, Brett SJ, 2019, A qualitative, grounded theory exploration of patients’ experience of early mobilisation, rehabilitation and recovery after critical illness, BMJ Open, Vol: 9, ISSN: 2044-6055

Rationale Physical rehabilitation (encompassing early mobilisation) of the critically ill patient is recognised best practice; however, further work is needed to explore the patients’ experience of rehabilitation qualitatively; a better understanding may facilitate implementation of early rehabilitation and elucidate the journey of survivorship.Objectives To explore patient experience of physical rehabilitation from critical illness during and after a stay on intensive care unit (ICU).Design Exploratory grounded theory study using semistructured interviews.Setting Adult medical/surgical ICU of a London teaching hospital.Participants A purposive sample of ICU survivors with intensive care unit acquired weakness (ICUAW) and an ICU length of stay of >72 hours.Analysis Data analysis followed a four-stage constant comparison technique: open coding, axial coding, selective coding and model development, with the aim of reaching thematic saturation. Peer debriefing and triangulation through a patient support group were carried out to ensure credibility.Main results Fifteen people were interviewed (with four relatives in attendance). The early rehabilitation period was characterised by episodic memory loss, hallucinations, weakness and fatigue, making early rehabilitation arduous and difficult to recall. Participants craved a paternalised approach to care in the early days of ICU.The central idea that emerged from this study was recalibration of the self. This is driven by a lost sense of self, with loss of autonomy and competence; dehumanised elements of care may contribute to this. Participants described a fractured life narrative due to episodic memory loss, meaning that patients were shocked on awakening from sedation by the discrepancy between their physical form and cognitive representation of themselves.Conclusions Recovery from ICUAW is a complex process that often begins with survivors exploring and adapting to a new body, followed by a period of rec

Journal article

Robinson M, Taylor J, Brett S, Nolan JP, Thomas M, Reeves B, Rogers CA, Voss S, Clout M, Benger JRet al., 2019, Design and implementation of a large and complex trial in emergency medical services, Trials, Vol: 20, ISSN: 1745-6215

BackgroundThe research study titled “Cluster randomised trial of the clinical and cost effectiveness of the i-gel supraglottic airway device versus tracheal intubation in the initial airway management of out-of-hospital cardiac arrest (AIRWAYS-2)” is a large-scale study being run in the English emergency medical (ambulance) services (EMS). It compares two airway management strategies (tracheal intubation and the i-gel) in out-of-hospital cardiac arrest. We describe the methods used to minimise bias and the challenges associated with the set-up, enrolment, and follow-up that were addressed.MethodsAIRWAYS-2 enrols adults without capacity when there is no opportunity to seek prior consent and when the intervention must be delivered immediately. We therefore adopted a cluster randomised design where the unit of randomisation is the individual EMS provider (paramedic). However, because paramedics could not be blinded to the intervention, it was necessary to automatically enrol all eligible patients in the study to avoid bias. Effective implementation required engagement with four large EMS and 95 receiving hospitals. Very high levels of data capture were required to ensure study integrity, and this necessitated collaborative working across multiple organisations. We sought to manage these processes by using a large and comprehensive electronic study database, implementing efficient trial procedures and comprehensive training.ResultsSuccessful implementation of the study design was facilitated by the approaches used. The necessary regulatory and ethical approvals to conduct the study were secured, and benefited from strong patient and public involvement. Early and continued consultation with decision makers within the four participating EMS resulted in a coordinated approach to study set-up. All receiving hospitals gave approval and agreed to collect data. A comprehensive database and programme of training and support were implemented. More than 1500 paramedic

Journal article

Corner E, Puthucheary Z, Cakiroglu A, Brett Set al., 2019, Early Functional Recovery Trajectories of Chronic Critically Ill Patients: An Observational Cohort Study, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Meiring C, Dixit A, Harris S, MacCallum NS, Brealey DA, Watkinson PJ, Jones A, Ashworth S, Beale R, Brett SJ, Singer S, Ercole Aet al., 2018, Optimal intensive care outcome prediction over time using machine learning, PLoS ONE, Vol: 13, ISSN: 1932-6203

BackgroundPrognostication is an essential tool for risk adjustment and decision making in the intensive care unit (ICU). Research into prognostication in ICU has so far been limited to data from admission or the first 24 hours. Most ICU admissions last longer than this, decisions are made throughout an admission, and some admissions are explicitly intended as time-limited prognostic trials. Despite this, temporal changes in prognostic ability during ICU admission has received little attention to date. Current predictive models, in the form of prognostic clinical tools, are typically derived from linear models and do not explicitly handle incremental information from trends. Machine learning (ML) allows predictive models to be developed which use non-linear predictors and complex interactions between variables, thus allowing incorporation of trends in measured variables over time; this has made it possible to investigate prognosis throughout an admission.Methods and findingsThis study uses ML to assess the predictability of ICU mortality as a function of time. Logistic regression against physiological data alone outperformed APACHE-II and demonstrated several important interactions including between lactate & noradrenaline dose, between lactate & MAP, and between age & MAP consistent with the current sepsis definitions. ML models consistently outperformed logistic regression with Deep Learning giving the best results. Predictive power was maximal on the second day and was further improved by incorporating trend data. Using a limited range of physiological and demographic variables, the best machine learning model on the first day showed an area under the receiver-operator characteristic curve (AUC) of 0.883 (σ = 0.008), compared to 0.846 (σ = 0.010) for a logistic regression from the same predictors and 0.836 (σ = 0.007) for a logistic regression based on the APACHE-II score. Adding information gathered on the second day of admission imp

Journal article

Gross J, Williams B, Fade P, Brett SJet al., 2018, Intensive care: balancing risk and benefit to facilitate informed decisions, British Medical Journal, Vol: 363, ISSN: 0959-8138

Journal article

Lipman J, Brett SJ, De Waele J, Osbert Cota M, Davis J, Finfer S, Glass P, Knowles S, McGuiness S, Myburgh J, Paterson D, Peake S, Rajbhandari D, Rhodes A, Roberts J, Shirwadkar C, Starr T, Taylor C, Billott L, Joel Det al., 2019, A protocol for a Phase 3 multicentre randomised controlled trial of continuous versus intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis: the BLING III trial, Critical Care and Resuscitation, ISSN: 1441-2772

ackground and rationale:Beta-lactam antibiotics displaya time-dependent mechanism of action with evidence suggesting improved outcomes when administering these drugs via continuous infusion as compared with standard intermittent infusion. However, there is no phase 3randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis.Design and setting:BLING III is a prospective, multicentre, open, phase 3RCT to compare continuous infusion with standard intermittent infusion of beta-lactam antibiotics in critically ill patients with sepsis.The study will be conducted in approximately 70 Intensive Care Units (ICUs) in Australia, New Zealand, United Kingdom, Belgium and selected other countries from 2018 to 2021.Participants and interventions: BLING IIIwill recruit 7000 critically illpatients with sepsis being treated with one of two beta-lactam antibiotics (piperacillin-tazobactam ormeropenem) to receive the beta-lactam antibiotic by either continuous or intermittentinfusion.Main outcome measures: The primary outcome isall-cause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 post randomisation, new acquisition, colonisation or infection with a multi-resistant organism or Clostridium difficilediarrhoea up to 14 days post randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation andduration of renal replacement therapy up to 90 days after randomisation.Results and conclusions: The BLING IIIstudy will compare the effect on 90-day mortality of beta-lactam antibiotics administered via continuous vs. intermittent infusion in 7000 critically ill patients with sepsis.

Journal article

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