Publications by authors named "Tony Whitehouse"

41 Publications

Study into the reversal of septic shock with landiolol (beta blockade): STRESS-L Study protocol for a randomised trial.

BMJ Open 2021 Feb 16;11(2):e043194. Epub 2021 Feb 16.

Department of Critical Care and Anaesthesia, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

Introduction: In 2013, a single-centre study reported the safe use of esmolol in patients with septic shock and tachycardia who required vasopressor therapy for more than 24 hours. Although not powered to detect a change in mortality, marked improvements were seen in survival (adjusted HR, 0.39; 95% CI, 0.26 to 0.59; p<0.001). Beta blockers are one of the most studied groups of drugs but their effect in septic shock is poorly understood; proposed mechanisms include not only the modulation of cardiac function but also immunomodulation.

Methods And Analysis: STRESS-L is a randomised, open-label, non-blinded clinical trial which is enrolling a total of 340 patients with septic shock as defined by Sepsis-3 consensus definition and a tachycardia (heart rate ≥95 beats per minute (bpm)) after vasopressor treatment of at least 24 hours. Standard randomisation (1:1 ratio) allocates patients to receive usual care (according to international standards) versus usual care and a continuous landiolol infusion to reduce the heart rate between 80 and 94 bpm. The primary endpoint is the mean Sequential Organ Failure Assessment score over 14 days from entry into the trial and while in intensive care unit. Results will inform current clinical practice guidelines.

Ethics And Dissemination: This trial has clinical trial authorisation from the UK competent authority, the Medicines and Healthcare products Regulatory Agency, and has been approved by the East of England-Essex Research Ethics Committee (reference: 17/EE/0368).The results of the trial will be reported first to trial collaborators. The main report will be drafted by the trial coordinating team, and the final version will be agreed by the Trial Steering Committee before submission for publication, on behalf of the collaboration.

Registration: The trial is funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) (Project Number: EME-14/150/85) and registered ISRCTN12600919 and EudraCT: 2017-001785-14.
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http://dx.doi.org/10.1136/bmjopen-2020-043194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888319PMC
February 2021

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

BMJ Open Qual 2020 12;9(4)

Department of Critical Care and Anaesthesia, Queen Elizabeth Hospital Birmingham, Birmingham, UK

Objectives: To safely expand and adapt the normal workings of a large critical care unit in response to the COVID-19 pandemic.

Methods: In April 2020, UK health systems were challenged to expand critical care capacity rapidly during the first wave of the COVID-19 pandemic so that they could accommodate patients with respiratory and multiple organ failure. Here, we describe the preparation and adaptive responses of a large critical care unit to the oncoming burden of disease. Our changes were similar to the revolution in manufacturing brought about by 'Long Shops' of 1853 when Richard Garrett and Sons of Leiston started mass manufacture of traction engines. This innovation broke the whole process into smaller parts and increased productivity. When applied to COVID-19 preparations, an assembly line approach had the advantage that our ICU became easily scalable to manage an influx of additional staff as well as the increase in admissions. Healthcare professionals could be replaced in case of absence and training focused on a smaller number of tasks.

Results: Compared with the equivalent period in 2019, the ICU provided 30.9% more patient days (2599 to 3402), 1845 of which were ventilated days (compared with 694 in 2019, 165.8% increase) while time from first referral to ICU admission reduced from 193.8±123.8 min (±SD) to 110.7±76.75 min (±SD). Throughout, ICU maintained adequate capacity and also accepted patients from neighbouring hospitals. This was done by managing an additional 205 doctors (70% increase), 168 nurses who had previously worked in ICU and another 261 nurses deployed from other parts of the hospital (82% increase).Our large tertiary hospital ensured a dedicated non-COVID ICU was staffed and equipped to take regional emergency referrals so that those patients requiring specialist surgery and treatment were treated throughout the COVID-19 pandemic.

Conclusions: We report how the challenge of managing a huge influx of patients and redeployed staff was met by deconstructing ICU care into its constituent parts. Although reported from the largest colocated ICU in the UK, we believe that this offers solutions to ICUs of all sizes and may provide a generalisable model for critical care pandemic surge planning.
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http://dx.doi.org/10.1136/bmjoq-2020-001117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722360PMC
December 2020

Ensemble learning for poor prognosis predictions: A case study on SARS-CoV-2.

J Am Med Inform Assoc 2021 03;28(4):791-800

Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.

Objective: Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning.

Materials And Methods: In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness.

Results: Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts.

Discussion: When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies.

Conclusions: Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients.
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http://dx.doi.org/10.1093/jamia/ocaa295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717299PMC
March 2021

Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19.

N Engl J Med 2020 Nov 8;383(21):2030-2040. Epub 2020 Oct 8.

The affiliations of the members of the writing committee are as follows: the Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine (P.H., J.T., J.A.W., N.J.W.), Nuffield Department of Population Health (M.M., L.L., J.L.B., N.S., J.R.E., E.J., R.H., M.J.L.), the Medical Research Council (MRC) Population Health Research Unit (N.S., J.R.E., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J., M.J.L.), and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester (M.W.), the Regional Infectious Diseases Unit, North Manchester General Hospital (A.U.), University of Manchester (A.U., T.F.), and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (T.W.), James Cook University Hospital, Middlesbrough (J.W.), North West Anglia NHS Foundation Trust, Peterborough (J.F.), the Department of Infectious Diseases, Cardiff and Vale University Health Board, and the Division of Infection and Immunity, Cardiff University, Cardiff (J.U.), Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K.R.), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M., E.J.), Nottingham - all in the United Kingdom; and the Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand (J.T., J.A.W., N.J.W.).

Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.

Methods: In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.

Results: The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.

Conclusions: Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).
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http://dx.doi.org/10.1056/NEJMoa2022926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556338PMC
November 2020

Acute-on-chronic liver failure: to admit to intensive care or not?

Br J Hosp Med (Lond) 2020 Sep 7;81(9):1-6. Epub 2020 Sep 7.

Department of Critical Care, University Hospital Birmingham, Birmingham, UK.

Acute-on-chronic liver failure is used to describe an acute decline in liver function in a patient with existing liver disease combined with other organ failure. Acute-on-chronic liver failure is associated with high short-term mortality, and the greater the number and severity of organ failures, the higher the mortality. The most commonly identified precipitants of acute-on-chronic liver failure include bacterial infection, gastrointestinal haemorrhage, viral hepatitis and recent excessive alcohol intake. Since some of these aetiologies are treatable, organ failure may return to pre-decompensation levels in up to 55% of patients. As a result, a trial of critical care treatment may be appropriate for many of these patients. Clinical scoring tools may help clinicians recognise futility, allowing timely withdrawal of organ support and shifting the focus of care toward palliation.
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http://dx.doi.org/10.12968/hmed.2020.0310DOI Listing
September 2020

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

Ann Am Thorac Soc 2021 01;18(1):122-129

Department of Critical Care, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

Patients with severe coronavirus disease (COVID-19) have complex organ support needs that necessitate prolonged stays in the intensive care unit (ICU), likely to result in a high incidence of neuromuscular weakness and loss of well-being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations. To describe the demographics, clinical status, level of rehabilitation, and mobility status at ICU discharge of patients with COVID-19. Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. Rehabilitation status was measured daily using the Manchester Mobility Score to identify the time taken to first mobilize (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge. A total of  = 177 patients were identified, of whom  = 110 survived to ICU discharge and were included in the subsequent analysis. While on ICU, patients required prolonged periods of mechanical ventilation (mean 19 ± 10 d), most received neuromuscular blockade (90%) and 67% were placed in the prone position on at least one occasion. The mean ± standard deviation time to first mobilize was 14 ± 7 days, with a median Manchester Mobility Score at ICU discharge of 5 (interquartile range: 4-6), which represents participants able to stand and step around to a chair with or without assistance. Time to mobilize was significantly longer in those with higher body mass index ( < 0.001), and older patients ( = 0.012) and those with more comorbidities ( = 0.017) were more likely to require further rehabilitation after discharge. The early experience of the COVID-19 pandemic in the United Kingdom resembles the experience in other countries, with high acuity of illness and prolonged period of mechanical ventilation required for those patients admitted to the ICU. Although the time to commence rehabilitation was delayed owing to this severity of illness, rehabilitation was possible within the ICU and led to increased levels of mobility from waking before ICU discharge.Clinical trial registered with ClinicalTrials.gov (NCT04396197).
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http://dx.doi.org/10.1513/AnnalsATS.202005-560OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780973PMC
January 2021

β-blockade in sepsis: regulation of persisting sepsis-related tachycardia.

Lancet Respir Med 2020 09 31;8(9):833-834. Epub 2020 Mar 31.

Department of Anesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Protestant Hospital of the Bethel Foundation, Bielefeld, Germany.

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http://dx.doi.org/10.1016/S2213-2600(20)30063-1DOI Listing
September 2020

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

Microb Genom 2019 09 11;5(9). Epub 2019 Sep 11.

Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW, UK.

Among long-stay critically ill patients in the adult intensive care unit (ICU), there are often marked changes in the complexity of the gut microbiota. However, it remains unclear whether such patients might benefit from enhanced surveillance or from interventions targeting the gut microbiota or the pathogens therein. We therefore undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses. Two-thirds of the patients experienced a marked drop in gut microbial diversity (to an inverse Simpson's index of <4) at some stage during their stay in the ICU, often accompanied by the absence or loss of potentially beneficial bacteria. Intravenous administration of the broad-spectrum antimicrobial agent meropenem was significantly associated with loss of gut microbial diversity, but the administration of other antibiotics, including piperacillin/tazobactam, failed to trigger statistically detectable changes in microbial diversity. In three-quarters of ICU patients, we documented episodes of gut domination by pathogenic strains, with evidence of cryptic nosocomial transmission of . In some patients, we also saw an increase in the relative abundance of apparent commensal organisms in the gut microbiome, including the archaeal species . In conclusion, we have documented a dramatic absence of microbial diversity and pathogen domination of the gut microbiota in a high proportion of critically ill patients using shotgun metagenomics.
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http://dx.doi.org/10.1099/mgen.0.000293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807385PMC
September 2019

A clinical evaluation of two central venous catheter stabilization systems.

Ann Intensive Care 2019 Apr 17;9(1):49. Epub 2019 Apr 17.

Corporate Division, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB, UK.

Background: Central venous catheters (CVCs) are commonly secured with sutures which are associated with microbial colonization and infection. We report a comparison of a suture-free system with standard sutures for securing short-term CVC in an international multicentre, prospective, randomized, non-blinded, observational feasibility study. Consented critical care patients who had a CVC inserted as part of their clinical management were randomized to receive either sutures or the suture-free system to secure their CVC. The main outcome measures were CVC migration (daily measurement of catheter movement) and unplanned catheter removals.

Results: The per cent of unplanned CVC removal in the two study groups was 2% (suture group 2 out of 86 patients) and 6% (suture-free group 5 out of 85 patients). Both securement methods were well tolerated in terms of skin irritation. The time and ease of application and removal of either securement systems were not rated significantly different. There was also no significant difference in CVC migration between the two securement systems in exploratory univariate and multivariate analyses. Overall, 42% (36 out of 86) of the CVC secured with sutures and 56% (48 out of 85) of the CVC secured with the suture-free securement system had CVC migration of ≥ 2 mm.

Conclusions: The two securement systems performed similarly in terms of CVC migration and unplanned removal of CVC; however, the feasibility study was not powered to detect statistically significant differences in these two parameters.

Trial Registration: ISRCTN, ISRCTN13939744. Registered 9 July 2015, http://www.isrctn.com/ISRCTN13939744 .
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http://dx.doi.org/10.1186/s13613-019-0519-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470223PMC
April 2019

Landiolol for managing atrial fibrillation in intensive care.

Eur Heart J Suppl 2018 Jan 8;20(Suppl A):A15-A18. Epub 2018 Jan 8.

Department of Anesthesiology and Intensive Care Medicine, University of Rome "La Sapienza", Italy Policlinico Umberto I° Hospital, Viale del Policlinico 155, Rome, Italy.

Landiolol is an injectable ultrashort acting beta-blocker with high beta1 selectivity indicated for heart rate control of atrial fibrillation in the emergency and critical care setting. Accordingly, landiolol is associated with a significantly reduced risk of arterial hypotension and negative inotropic effects. Based on this particular profile along with the clinical experience in Japan for more than a decade landiolol represents a promising agent for the management of elevated heart rate and atrial fibrillation in intensive care patients even with catecholamine requirements. This article provides a review and perspective of landiolol for heart rate control in intensive care patients based on the current literature.
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http://dx.doi.org/10.1093/eurheartj/sux039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909768PMC
January 2018

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

Crit Care Med 2018 12;46(12):1969-1976

Department of Critical Care Medicine, University Hospital of Birmingham NHS trust, Birmingham, United Kingdom.

Objectives: In various medical and surgical conditions, research has found that centers with higher patient volumes have better outcomes. This relationship has not previously been explored for status epilepticus. This study sought to examine whether centers that see higher volumes of patients with status epilepticus have lower in-hospital mortality than low-volume centers.

Design: Cohort study, using 2010-2015 data from the nationwide Case Mix Programme database of the U.K.'s Intensive Care National Audit and Research Centre.

Setting: Greater than 90% of ICUs in United Kingdom, Wales, and Northern Ireland.

Patients: Twenty-thousand nine-hundred twenty-two adult critical care admissions with a primary or secondary diagnosis of status epilepticus or prolonged seizure.

Interventions: Annual hospital status epilepticus admission volume.

Measurements And Main Results: We used multiple logistic regression to evaluate the association between hospital annual status epilepticus admission volume and in-hospital mortality. Hospital volume was modeled as a nonlinear variable using restricted cubic splines, and generalized estimating equations with robust SEs were used to account for clustering by institution. There were 2,462 in-hospital deaths (11.8%). There was no significant association between treatment volume and in-hospital mortality for status epilepticus (p = 0.54). This conclusion was unchanged across a number of subgroup and sensitivity analyses, although we lacked data on seizure duration and medication use. Secondary analyses suggest that many high-risk patients were already transferred from low- to high-volume centers.

Conclusions: We find no evidence that higher volume centers are associated with lower mortality in status epilepticus overall. It is likely that national guidelines and local pathways in the United Kingdom allow efficient patient transfer from smaller centers like district general hospitals to provide satisfactory patient care in status epilepticus. Future research using more granular data should explore this association for the subgroup of patients with refractory and superrefractory status epilepticus.
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http://dx.doi.org/10.1097/CCM.0000000000003392DOI Listing
December 2018

The ten tips to manage critically ill patients with acute-on-chronic liver failure.

Intensive Care Med 2018 Nov 31;44(11):1932-1935. Epub 2018 Jan 31.

Department of Critical Care, Kings College Hospital Foundation Trust, London, UK.

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http://dx.doi.org/10.1007/s00134-018-5078-zDOI Listing
November 2018

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

J Crit Care 2018 04 4;44:407-412. Epub 2018 Jan 4.

Department of Critical Care, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, United Kingdom.

Background: Systematic reviews of early rehabilitation within intensive care units have highlighted the need for robust multi-centre randomised controlled trials with longer term follow up. This trial aims to explore the feasibility of earlier and enhanced rehabilitation for patients mechanically ventilated for ≥5days and to assess the impact on possible long term outcome measures for use in a definitive trial.

Methods: Patients admitted to a large UK based intensive care unit and invasively ventilated for ≥5days were randomised to the rehabilitation intervention or standard care on a 1:1 basis, stratified by age and SOFA score. The rehabilitation intervention involved a structured programme, with progression along a functionally based mobility protocol according to set safety criteria.

Results: 103 out of 128 eligible patients were recruited into the trial, achieving an initial recruitment rate of 80%. Patients in the intervention arm mobilized significantly earlier (8days vs 10 days, p=0.035), at a more acute phase of illness (SOFA 6 vs 4, p<0.05) and reached a higher level of mobility at the point of critical care discharge (MMS 7 vs 5, p<0.01).

Conclusion: We have demonstrated the feasibility of introducing a structured programme of rehabilitation for patients admitted to critical care.
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http://dx.doi.org/10.1016/j.jcrc.2018.01.001DOI Listing
April 2018

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

Pilot Feasibility Stud 2017 17;3:19. Epub 2017 Apr 17.

Therapy Services, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham, UK.

Background: Mortality from critical illness is improving, but survivors suffer from prolonged weakness and psychological and cognitive impairments. Maximising the recovery after critical illness has been highlighted as a research priority, especially in relation to an ageing population who present with higher rates of pre-morbid disability. Small studies have shown that starting rehabilitation early within the intensive care unit (ICU) improves short-term outcomes. Systematic reviews have highlighted the need for robust multicentre randomised controlled trials with longer term follow-up.

Methods: The study design is a randomised controlled study to explore the feasibility of providing earlier and enhanced rehabilitation to mechanically ventilated patients at high risk of ICU-acquired weakness within the ICU. The rehabilitation intervention involves a structured programme, with progression along a functionally based mobility protocol according to set safety criteria. The overall aim of the intervention is to commence mobilisation at an earlier time point in the patient's illness and increase mobility of the patient through their recovery trajectory. Participants will be randomised to enhanced rehabilitation or standard care, with the aim of recruiting at least 100 patients over 16 months. The trial design will assess recruitment and consent rates from eligible patients, compliance with the intervention, and assess a range of possible outcome measures for use in a definitive trial, with follow-up continuing for 12 months post hospital discharge.

Discussion: This study will evaluate the feasibility of providing an earlier and enhanced rehabilitation intervention to mechanically ventilated patients in critical care. We will identify strengths and weaknesses of the proposed protocol and the utility and characteristics of the outcome measures. The results from this study will inform the design of a phase III multicentre trial of enhanced rehabilitation for critically ill adults.

Trial Registration: ISRCTN90103222, 13/08/2015; retrospectively registered.
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http://dx.doi.org/10.1186/s40814-017-0131-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393007PMC
April 2017

The Association Between Visiting Intensivists and ICU Outcomes.

Crit Care Med 2017 Jun;45(6):949-955

1Department of Critical Care and Anaesthesia, University Hospital Birmingham, Edgbaston, Birmingham, United Kingdom. 2University Department of Anaesthesia & Critical Care, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom. 3Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, ON, Canada.

Objectives: We hypothesized that intensivists unfamiliar with an ICU team and the context of that ICU would affect patient outcomes. We examined differences in mortality when ICU patients were admitted under intensivists routinely working in that ICU and compared with those admitted by intensivists familiar with an ICU elsewhere in the same hospital.

Design, Settings, And Patients: A 5-year natural experimental crossover study involving patients admitted to four ICUs in a large U.K. teaching hospital.

Interventions: During a period of service reconfiguration, intensivists routinely rostered to work in one ICU worked in another of the hospital's four ICUs. "Home" intensivists were those who continued to work in their usual ICU; "visitor" intensivists were those who delivered care in an unfamiliar ICU. Patient data were obtained from electronic patient records to provide analysis on sex, age, admission Sequential Organ Failure Assessment score, date and time of admission, and admission type (elective, transfer, or unplanned).

Measurements And Main Results: We analyzed 9,981 admissions to four separate ICUs over a 5-year period. In total, 34.5% of patients were admitted by intensivists working in nonfamiliar surroundings. Visitor intensivists admitted patients with similar age and gender distributions but with greater physiologic derangement (mean Sequential Organ Failure Assessment score, 4.1 ± 2.8 vs 3.9 ± 2.8; p < 0.001) than home intensivists. Overall ICU mortality rates were higher in visitor intensivists, albeit not significantly so (11.5% vs 10.2%; p = 0.052). However, when the ICUs were analyzed separately, visitor mortality rates were found to be significantly higher than for home intensivists in two of the four ICUs (p = 0.017, 0.006). A multivariable analysis adjusting for confounding factors and the clustering of consultants revealed that the overall mortality rate was significantly higher for visitors (odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.024). A significant interaction between the ICU and visitor status was also detected (p = 0.046), with the visitor effect remaining significant in the two ICUs identified previously (both p = 0.009).

Conclusions: Visitor intensivists in some ICUs were associated with higher mortality. The reasons are unknown but could relate to intensivists' practices, unfamiliarity with the patients, or the interaction with the interprofessional team.
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http://dx.doi.org/10.1097/CCM.0000000000002373DOI Listing
June 2017

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines.

Intensive Care Med 2017 Mar 6;43(3):380-398. Epub 2017 Feb 6.

Department of Intensive Care Medicine, VU University Medical Center, Amsterdam, The Netherlands.

Purpose: To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.

Methods: We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds.

Results: We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion.

Conclusions: We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.
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http://dx.doi.org/10.1007/s00134-016-4665-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323492PMC
March 2017

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

Indian J Crit Care Med 2016 Sep;20(9):534-41

Department of Critical Care, Queen Elizabeth Medical Centre, Birmingham, B15 2TH, UK; Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK; School of Immunity and Infection, University of Birmingham, B15 2TT, UK.

Objectives: Sepsis is a common cause of morbidity and mortality and is associated with significant costs to the healthcare organizations. We performed a systematic review and meta-analysis to assess whether high or low-dose statin therapy improved mortality in patients with sepsis.

Methods: The trials analyzed in this study were multicenter or single center randomized control studies using statins for sepsis in a hospital setting. The patients included were adults with suspected or confirmed infection.

Interventions: This study found eight randomized controlled trials where participants were given either a statin or placebo daily for 14-28 days, the duration of their illness, or until their death or discharge, which ever occurred first.

Primary And Secondary Outcomes Measured: This meta-analysis measured the effect of statin therapy on in hospital and 28 days mortality.

Results: In unselected patients, there was no demonstrable difference in the 28 days mortality (relative risk [RR] 0.88 95% confidence interval [CI], 0.70-1.12 and P = 0.16). There was also no significant difference between statin versus placebo for in-hospital mortality (RR 0.98 95% CI, 0.85-1.14 P = 0.36). When the studies where divided into low-dose and high-dose groups, there were no statistically significant differences for in-hospital mortality between low-dose statin versus placebo for (RR 0.81 CI 0.44-1.49 P = 0.27) or high-dose statin versus placebo (RR 0.99 95% CI 0.85-1.16, P = 0.28). There was no significant difference in adverse effects between the high- and low-dose groups.

Conclusions: In this meta-analysis, we found that the use of statins did not significantly improve either in-hospital mortality or 28-day mortality in patients with sepsis. In the low-dose group, there were fewer quality multicenter studies; hence, conclusions based on the results of this subgroup are limited.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027747PMC
http://dx.doi.org/10.4103/0972-5229.190366DOI Listing
September 2016

Economic impact of Tegaderm chlorhexidine gluconate (CHG) dressing in critically ill patients.

J Infect Prev 2016 09 13;17(5):216-223. Epub 2016 Jul 13.

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK.

Purpose: To estimate the economic impact of a Tegaderm chlorhexidine gluconate (CHG) gel dressing compared with a standard intravenous (i.v.) dressing (defined as non-antimicrobial transparent film dressing), used for insertion site care of short-term central venous and arterial catheters (intravascular catheters) in adult critical care patients using a cost-consequence model populated with data from published sources.

Material And Methods: A decision analytical cost-consequence model was developed which assigned each patient with an indwelling intravascular catheter and a standard dressing, a baseline risk of associated dermatitis, local infection at the catheter insertion site and catheter-related bloodstream infections (CRBSI), estimated from published secondary sources. The risks of these events for patients with a Tegaderm CHG were estimated by applying the effectiveness parameters from the clinical review to the baseline risks. Costs were accrued through costs of intervention (i.e. Tegaderm CHG or standard intravenous dressing) and hospital treatment costs depended on whether the patients had local dermatitis, local infection or CRBSI. Total costs were estimated as mean values of 10,000 probabilistic sensitivity analysis (PSA) runs.

Results: Tegaderm CHG resulted in an average cost-saving of £77 per patient in an intensive care unit. Tegaderm CHG also has a 98.5% probability of being cost-saving compared to standard i.v. dressings.

Conclusions: The analyses suggest that Tegaderm CHG is a cost-saving strategy to reduce CRBSI and the results were robust to sensitivity analyses.
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http://dx.doi.org/10.1177/1757177416657162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994702PMC
September 2016

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

Indian J Crit Care Med 2016 May;20(5):280-4

Department of Critical Care Medicine, Critical Care Unit, Queen Elizabeth Hospital, University Hospital of Birmingham NHS Foundation Trust, Birmingham, UK; Department of Medicine, Division of Anaesthesia, University of Cambridge, Cambridge, UK.

Tracheostomy is one of the most common procedures undertaken in critically ill patients. It offers many theoretical advantages over translaryngeal intubation. Recent evidence in a heterogeneous group of critically ill patients, however, has not demonstrated a benefit for tracheostomy, in terms of mortality, length of stay in Intensive Care Unit (ICU), or incidence of ventilator-associated pneumonia. It may be a beneficial intervention in articular subsets of ICU patients. In this article, we will focus on the evidence for the timing of tracheostomy and its effect on various subgroups of patients in critical care.
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http://dx.doi.org/10.4103/0972-5229.182202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876649PMC
May 2016

A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure.

J Hepatol 2016 08 12;65(2):273-9. Epub 2016 Mar 12.

Department of Hepatology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Background & Aims: Animal models and human case series of acute liver failure (ALF) suggest moderate hypothermia (MH) to have protective effects against cerebral oedema (CO) development and intracranial hypertension (ICH). However, the optimum temperature for patient management is unknown. In a prospective randomized controlled trial we investigated if maintenance of MH prevented development of ICH in ALF patients at high risk of the complication.

Methods: Patients with ALF, high-grade encephalopathy and intracranial pressure (ICP) monitoring in specialist intensive care units were randomized by sealed envelope to targeted temperature management (TTM) groups of 34°C (MH) or 36°C (control) for a period of 72h. Investigators were not blinded to group assignment. The primary outcome was a sustained elevation in ICP >25mmHg, with secondary outcomes the occurrence of predefined serious adverse effects, magnitude of ICP elevations and cerebral and all-cause hospital mortality (with or without transplantation).

Results: Forty-six patients were randomized, of whom forty-three were studied. There was no significant difference between the TTM groups in the primary outcome during the study period (35% vs. 27%, p=0.56), for the MH (n=17) or control (n=26) groups respectively, relative risk 1.31 (95% CI 0.53-3.2). Groups had similar incidence of adverse events and overall mortality (41% vs. 46%, p=0.75).

Conclusions: In patients with ALF at high risk of ICH, MH at 33-34°C did not confer a benefit above management at 36°C in prevention of ICH or in overall survival. This study did not confirm advantage of its prophylactic use. (ISRCTN registration number 74268282; no funding.)

Lay Summary: Studies in animals with acute liver failure (ALF) have suggested that cooling (hypothermia) could prevent or limit the development of brain swelling, a dangerous complication of the condition. There is limited data on its effects in humans. In a randomized controlled trial in severely ill patients with ALF we compared the effects of different temperatures and found no benefit on improving survival or preventing brain swelling by controlling temperature at 33-34°C against 36°C.
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http://dx.doi.org/10.1016/j.jhep.2016.03.003DOI Listing
August 2016

LiFe: a liver injury score to predict outcome in critically ill patients.

Intensive Care Med 2016 Mar 28;42(3):361-369. Epub 2016 Jan 28.

The Nathan E. Hellman Memorial Laboratory, Renal Division, Brigham and Women's Hospital, 75 Francis Street, MRB 418, Boston, MA, 02115, USA.

Purpose: To develop a liver function-related risk prediction tool to identify acute-on-chronic liver failure patients at greatest risk of in-hospital mortality.

Methods: The LiFe (liver, injury, failure, evaluation) score, was constructed based on the opinions of 157 intensivists within the European Society for Intensive Care Medicine. Experts were surveyed and instructed to weigh the diagnostic importance of each feature of a proposed prediction model. We performed a retrospective cohort study of 1916 patients with chronic liver disease admitted to a medical or surgical ICU between 1997, and 2011 in three large hospitals in Boston, USA, and London, UK, with arterial lactate, total bilirubin and INR drawn at ICU admission. The derivation cohort consisted of ICU patients from Brigham and Women's Hospital and Massachusetts General Hospital in Boston (n = 945), and the validation cohort comprised patients from Kings College Hospital, London, admitted to the Liver Intensive Therapy Unit (n = 971). A clinical prediction model was derived and validated based on a logistic regression model describing the risk of in-hospital mortality as a function of the predictors (arterial lactate 0-1.9, ≥2.0-3.9, ≥4.0-5.9, ≥6.0 mg/dL; total bilirubin 0-1.9, ≥2.0-3.9, ≥4.0-5.9, ≥6.0 mg/dL; INR 0-1.9, ≥2.0-3.9, ≥4.0-5.9, ≥6.0) at ICU admission. Performance analysis of the LiFe score against SOFA, CLIF-SOFA, APACHE II and SAPS II was completed in the validation cohort of critically ill cirrhotic patients.

Results: The derivation cohort (n = 941) was 53% male with a mean age of 65 years and an in-hospital mortality rate of 30%. The validation cohort (n = 971) was 63% male with mean age of 51 years and an in-hospital mortality rate of 52%. The C statistic for the prediction model was 0.74 (95% CI 0.70-0.77) in the derivation cohort and 0.77 (95% CI 0.74-0.80) in the validation cohort. In the validation cohort, in-hospital mortality was 17% in the low-risk group (0 risk score points), 28% in the intermediate-risk group (1-3 points), 47% in the high-risk group (4-8 points), and 77% in the very high-risk group (>8 points). In the validation cohort, the C statistics for SOFA, CLIF-SOFA, APACHE II, and SAPS II were 0.80, 0.81, 0.77, and 0.78, respectively. Further, a significant positive correlation exists between LiFe score and acute-on-chronic liver failure grade, (r = 0.478, P < 0.001).

Conclusions: Our LiFe score calculated from arterial lactate, total bilirubin and INR at ICU admission is a simple, quick and easily understandable score that may increase clinical utility for risk prediction in ICU patients with acute-on-chronic liver failure. The LiFe score can be used in place of physiological based scores for early risk prediction in patients with chronic liver disease but is not intended to replace CLIF-SOFA as a benchmark for prognostication.
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http://dx.doi.org/10.1007/s00134-015-4203-5DOI Listing
March 2016

The ageing population is neglected in research studies of traumatic brain injury.

Br J Neurosurg 2016 8;30(2):221-6. Epub 2016 Jan 8.

a Neurocritical Care Unit, Cambridge University Hospitals NHS Trust , Cambridge, Cambridgeshire , UK ;

Introduction: The UK population is ageing with increasing number of elderly patients suffering traumatic brain injury (TBI). The purpose of this study was to identify national TBI admission demographics, analyse the temporal evolution of TBI mortality in a single centre and conduct a systematic review of the literature to identify whether there is an age bias amongst researchers studying TBI.

Methods: National demographics for TBI were obtained from Health Episode Statistics. TBI patients admitted from 2000 to 2011 to Cambridge University Hospitals Neurocritical Care Unit (NCCU) were divided into age groups (<60, 60-74, ≥75 years). Temporal evolution of mortality was analysed using a logistic regression method. A systematic literature review was conducted to identify primary TBI research studies. Patient's ages were extracted and an average mean age was calculated and compared over time.

Results: From 1998, national TBI admissions have increased with the greatest rise in >60-year age group (p < 0.0001). In a tertiary referral critical care unit (n = 1145), the 60-74 year age group (compared to <60) had a significantly lower improvement in mortality over time (OR: 1.15, 95% CI: 1.02-1.31). A literature review revealed a mean age of 32.73 years (SD ± 12.85) for patients recruited to primary TBI studies.

Conclusion: Despite increased admissions of elderly patients following TBI and static mortality (single centre, 60-74 year age group) there is little or no evidence of a corresponding increase in the age of patients recruited for TBI studies. In addition to the difficulties this presents in forming evidence-based decisions for the patient with TBI, it may also represent a wider problem for ICU research in an ever-ageing critical care population. More research needs to be conducted to establish the treatment end points for an ageing population.
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http://dx.doi.org/10.3109/02688697.2015.1119240DOI Listing
January 2017

Is It Time to Beta Block the Septic Patient?

Biomed Res Int 2015 18;2015:424308. Epub 2015 Oct 18.

Department of Anaesthesia and Critical Care Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham B15 2GW, UK ; College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Beta blockers are some of the most studied drugs in the pharmacopoeia. They are already widely used in medicine for treating hypertension, chronic heart failure, tachyarrhythmias, and tremor. Whilst their use in the immediate perioperative patient has been questioned, the use of esmolol in the patients with established septic shock has been recently reported to have favourable outcomes. In this paper, we review the role of the adrenergic system in sepsis and the evidence for the use of beta stimulation and beta blockers from animal models to critically ill patients.
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http://dx.doi.org/10.1155/2015/424308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628753PMC
August 2016

Clinical evaluation of a chlorhexidine intravascular catheter gel dressing on short-term central venous catheters.

Am J Infect Control 2016 Jan 9;44(1):54-60. Epub 2015 Oct 9.

Corporate Division, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. Electronic address:

Background: A major source of microbial colonization of short-term central venous catheters (CVC) is the patients' endogenous skin microorganisms located at the CVC insertion site. The aim of this study was to determine if a transparent film dressing incorporating a 2% (weight/weight) chlorhexidine gluconate (CHG) gel decreases CVC and insertion site microbial colonization compared with a nonantimicrobial dressing in adult patients in critical care.

Methods: On CVC removal, samples for microbiological investigation were taken from both the skin surrounding the CVC insertion site and also from sutures securing the CVC. The sutures and intradermal and tip sections of the CVC were also collected for microbiological investigation. Microorganisms recovered from the samples were subsequently tested for susceptibility to CHG.

Results: There was a significant reduction in the number of microorganisms recovered from the CVC insertion site, suture site, sutures, and catheter surface in the CHG dressing group (n = 136) compared with the nonantimicrobial dressing group (n = 137). There was no significant difference in susceptibility to CHG between the microorganisms isolated from the CHG and standard dressing study patients.

Conclusion: A film dressing incorporating a CHG gel pad significantly reduced the number of microorganisms at the CVC insertion and suture sites with concomitant reduced catheter colonization.
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http://dx.doi.org/10.1016/j.ajic.2015.08.022DOI Listing
January 2016

Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion.

Int J Antimicrob Agents 2015 Sep 7;46(3):249-53. Epub 2015 Jun 7.

Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia. Electronic address:

Vancomycin is a glycopeptide antibiotic widely used in the management of meticillin-resistant Staphylococcus aureus (MRSA). Guidelines currently recommend vancomycin be administered by intermittent infusion, despite recent research suggesting that continuous infusion (CI) may be associated with lower rates of vancomycin-associated nephrotoxicity. In 2012, Cataldo et al. presented a meta-analysis supporting the use of CI. Here we present an updated meta-analysis, inclusive of a recently published large-scale retrospective study. PubMed, EMBASE and Cochrane Reviews databases were searched using the keywords 'vancomycin' and 'continuous' or 'intermittent' or 'infusion' or 'discontinuous' or 'administration'. Seven studies were included in the final analysis. Using a random-effects model, a non-significant trend of reduced nephrotoxicity in those who received vancomycin by CI (risk ratio=0.799, 95% confidence interval 0.523-1.220; P=0.299) was identified. A large, randomised controlled trial is necessary to confirm these results.
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http://dx.doi.org/10.1016/j.ijantimicag.2015.04.013DOI Listing
September 2015

The authors reply.

Crit Care Med 2015 May;43(5):e154-5

Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia, and Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Department of Anaesthesia and Critical Care, University Hospital Birmingham, Birmingham, Birmingham, United Kingdom Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia, and Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Department of Anaesthesia and Critical Care, University Hospital Birmingham, Birmingham, Birmingham, United Kingdom Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.

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http://dx.doi.org/10.1097/CCM.0000000000000952DOI Listing
May 2015

Monitoring-based antibiotic dose optimisation.

J Intensive Care Soc 2015 Feb 12;16(1):75-76. Epub 2014 Dec 12.

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http://dx.doi.org/10.1177/1751143714564512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593301PMC
February 2015

Enhancing rehabilitation of mechanically ventilated patients in the intensive care unit: a quality improvement project.

J Crit Care 2015 Feb 2;30(1):13-8. Epub 2014 Oct 2.

Critical Care, University Hospitals Birmingham NHS Foundation Trust, Queen ElizabethHospital Birmingham, Birmingham, UK.

Purpose: Prolonged periods of mechanical ventilation are associated with significant physical and psychosocial adverse effects. Despite increasing evidence supporting early rehabilitation strategies, uptake and delivery of such interventions in Europe have been variable. The objective of this study was to evaluate the impact of an early and enhanced rehabilitation program for mechanically ventilated patients in a large tertiary referral, mixed-population intensive care unit (ICU).

Method: A new supportive rehabilitation team was created within the ICU in April 2012, with a focus on promoting early and enhanced rehabilitation for patients at high risk for prolonged ICU and hospital stays. Baseline data on all patients invasively ventilated for at least 5 days in the previous 12 months (n = 290) were compared with all patients ventilated for at least 5 days in the 12 months after the introduction of the rehabilitation team (n = 292). The main outcome measures were mobility level at ICU discharge (assessed via the Manchester Mobility Score), mean ICU, and post-ICU length of stay (LOS), ventilator days, and in-hospital mortality.

Results: The introduction of the ICU rehabilitation team was associated with a significant increase in mobility at ICU discharge, and this was associated with a significant reduction in ICU LOS (16.9 vs 14.4 days, P = .007), ventilator days (11.7 vs 9.3 days, P < .05), total hospital LOS (35.3 vs 30.1 days, P < .001), and in-hospital mortality (39% vs 28%, P < .05).

Conclusion: A quality improvement strategy to promote early and enhanced rehabilitation within this European ICU improved levels of mobility at critical care discharge, and this was associated with reduced ICU and hospital LOS and reduced days of mechanical ventilation.
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http://dx.doi.org/10.1016/j.jcrc.2014.09.018DOI Listing
February 2015

Vancomycin-associated nephrotoxicity in the critically ill: a retrospective multivariate regression analysis*.

Crit Care Med 2014 Dec;42(12):2527-36

1Burns Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia. 2Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. 3Department of Anaesthesia and Critical Care, University Hospital Birmingham, Birmingham, United Kingdom.

Objectives: To evaluate the influence of vancomycin dose, serum trough concentration, and dosing strategy on the evolution of acute kidney injury in critically ill patients.

Design: Retrospective, single-center, observational study.

Setting: University Hospital ICU, Birmingham, UK.

Patients: All critically ill patients receiving vancomycin from December 1, 2004, to August 31, 2009.

Intervention: None.

Measurements And Main Results: The prevalence of new onset nephrotoxicity was reported using Risk, Injury, Failure, Loss, End-stage renal disease criteria, and independent factors predictive of nephrotoxicity were identified using logistic regression analysis. Complete data were available for 1,430 patients. Concomitant vasoactive therapy (odds ratio = 1.633; p < 0.001), median serum vancomycin (odds ratio = 1.112; p < 0.001), and duration of therapy (odds ratio = 1.041; p ≤ 0.001) were significant positive predictors of nephrotoxicity. Intermittent infusion was associated with a significantly greater risk of nephrotoxicity than continuous infusion (odds ratio = 8.204; p ≤ 0.001).

Conclusions: In a large dataset, higher serum vancomycin concentrations and greater duration of therapy are independently associated with increased odds of nephrotoxicity. Furthermore, continuous infusion is associated with a decreased likelihood of nephrotoxicity compared with intermittent infusion. This large dataset supports the use of continuous infusion of vancomycin in critically ill patients.
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http://dx.doi.org/10.1097/CCM.0000000000000514DOI Listing
December 2014