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1. Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial

Author

Rupert F. G. Simpson, Josef Dankiewicz, Grigoris V. Karamasis, Paolo Pelosi, Matthias Haenggi, Paul J. Young, Janus Christian Jakobsen, Jonathan Bannard-Smith, Pedro D. Wendel-Garcia, Fabio Silvio Taccone, Per Nordberg, Matt P. Wise, Anders M. Grejs, Gisela Lilja, Roy Bjørkholt Olsen, Alain Cariou, Jean Baptiste Lascarrou, Manoj Saxena, Jan Hovdenes, Matthew Thomas, Hans Friberg, John R. Davies, Niklas Nielsen, and Thomas R. Keeble

Subjects
Out of hospital cardiac arrest, Temperature management, Hypothermia, Time to target temperature, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes. Methods In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4–6 on modified Rankin scale). Results A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (p = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84–1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80–1.26). Conclusions Using a hospital’s average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.

Published
2022
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2. ClinCirc identifies alterations of the circadian peripheral oscillator in critical care patients

Author

Peter S. Cunningham, Gareth B. Kitchen, Callum Jackson, Stavros Papachristos, Thomas Springthorpe, David van Dellen, Julie Gibbs, Timothy W. Felton, Anthony J. Wilson, Jonathan Bannard-Smith, Martin K. Rutter, Thomas House, Paul Dark, Titus Augustine, Ozgur E. Akman, Andrew L. Hazel, and John F. Blaikley

Subjects
Inflammation, Transplantation, Medicine
Abstract

Background Assessing circadian rhythmicity from infrequently sampled data is challenging; however, these types of data are often encountered when measuring circadian transcripts in hospitalized patients.Methods We present ClinCirc. This method combines 2 existing mathematical methods (Lomb-Scargle periodogram and cosinor) sequentially and is designed to measure circadian oscillations from infrequently sampled clinical data. The accuracy of this method was compared against 9 other methods using simulated and frequently sampled biological data. ClinCirc was then evaluated in 13 intensive care unit (ICU) patients as well as in a separate cohort of 29 kidney-transplant recipients. Finally, the consequences of circadian alterations were investigated in a retrospective cohort of 726 kidney-transplant recipients.Results ClinCirc had comparable performance to existing methods for analyzing simulated data or clock transcript expression of healthy volunteers. It had improved accuracy compared with the cosinor method in evaluating circadian parameters in PER2:luc cell lines. In ICU patients, it was the only method investigated to suggest that loss of circadian oscillations in the peripheral oscillator was associated with inflammation, a feature widely reported in animal models. Additionally, ClinCirc was able to detect other circadian alterations, including a phase shift following kidney transplantation that was associated with the administration of glucocorticoids. This phase shift could explain why a significant complication of kidney transplantation (delayed graft dysfunction) oscillates according to the time of day kidney transplantation is performed.Conclusion ClinCirc analysis of the peripheral oscillator reveals important clinical associations in hospitalized patients.Funding UK Research and Innovation (UKRI), National Institute of Health Research (NIHR), Engineering and Physical Sciences Research Council (EPSRC), National Institute on Academic Anaesthesia (NIAA), Asthma+Lung UK, Kidneys for Life.

Published
2023
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3. The association of clinical frailty with outcomes of patients reviewed by rapid response teams: an international prospective observational cohort study

Author

Ralph K. L. So, Jonathan Bannard-Smith, Chris P. Subbe, Daryl A. Jones, Joost van Rosmalen, Geoffrey K. Lighthall, and the METHOD study investigators

Subjects
Frailty, Rapid response team, Acute illness, Advanced directives, Outreach team, Medical emergency team, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Frailty is a state of vulnerability to poor resolution of homeostasis after a stressor event and is strongly associated with adverse outcomes. Therefore, the assessment of frailty may be an essential part of evaluation in any healthcare encounter that might result in an escalation of care. The purpose of the study was to assess the frequency and association of frailty with clinical outcomes in patients subject to rapid response team (RRT) review. Methods In this multi-national prospective observational cohort study, centres with existing RRTs collected data over a 7-day period, with follow up of all patients at 24 h following their RRT call and at hospital discharge or 30 days following the event trigger (whichever came sooner). Investigators also collected data on the triggers and interventions provided and a bedside assessment on the level of patients’ frailty using a clinical frailty scale. Results Amongst 1133 patients, 40% were screened as frail, which was associated with older age (p

Published
2018
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4. Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomised clinical trial

Author

Jonathan A. Silversides, Ross McMullan, Lydia M. Emerson, Ian Bradbury, Jonathan Bannard-Smith, Tamas Szakmany, John Trinder, Anthony J. Rostron, Paul Johnston, Andrew J. Ferguson, Andrew J. Boyle, Bronagh Blackwood, John C. Marshall, and Daniel F. McAuley

Subjects
Oedema, Infusions, Fluid therapy, Critical illness, Diuretics, Intravenous, Critical Care and Intensive Care Medicine, Water–electrolyte balance, Deresuscitation, RT, RC
Abstract

PURPOSE: Fluid overload is common in critical illness and is associated with mortality. This study investigated the feasibility of a randomised trial comparing conservative fluid administration and deresuscitation (active removal of accumulated fluid using diuretics or ultrafiltration) with usual care in critical illness.METHODS: Open-label, parallel-group, allocation-concealed randomised clinical feasibility trial. Mechanically ventilated adult patients expected to require critical care beyond the next calendar day were enrolled between 24 and 48 h following admission to the intensive care unit (ICU). Patients were randomised to either a 2-stage fluid strategy comprising conservative fluid administration and, if fluid overload was present, active deresuscitation, or usual care. The primary endpoint was fluid balance in the 24 h up to the start of study day 3. Secondary endpoints included cumulative fluid balance, mortality, and duration of mechanical ventilation.RESULTS: One hundred and eighty patients were randomised. After withdrawal of 1 patient, 89 patients assigned to the intervention were compared with 90 patients assigned to the usual care group. The mean plus standard deviation (SD) 24-h fluid balance up to study day 3 was lower in the intervention group (- 840 ± 1746 mL) than the usual care group (+ 130 ± 1401 mL; P CONCLUSIONS: A strategy of conservative fluid administration and active deresuscitation is feasible, reduces fluid balance compared with usual care, and may cause benefit or harm. In view of wide variations in contemporary clinical practice, large, adequately powered trials investigating the clinical effectiveness of conservative fluid strategies in critically ill patients are warranted.

Published
2021
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6. Insulin therapy in organ donation and transplantation

Author

Titus Augustine, Martin K. Rutter, David van Dellen, Petros Yiannoullou, Jonathan Bannard-Smith, Iestyn M. Shapey, and Angela Summers

Subjects
Inotrope, insulin, medicine.medical_specialty, Tissue and Organ Procurement, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Islets of Langerhans Transplantation, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, organ donation, Internal Medicine, medicine, Humans, Insulin, Organ donation, Intensive care medicine, Physiological stress, business.industry, Organ Transplantation, Acute hyperkalaemia, Transplantation, Hyperglycemia, Critical illness, business, hyperglycaemia, transplantation
Abstract

Hyperglycaemia is common in hospitalized individuals, and is often caused by physiological stress associated with critical illness or major surgery. Insulin therapy is an established treatment for hyperglycaemia and acute hyperkalaemia, and has also been used for myocardial dysfunction resistant to inotropic support. Insulin is commonly used in both organ donors and transplant recipients for hyperglycaemia, but the underlying knowledge base supporting its use remains limited. Insulin therapy plays an important yet poorly understood role in both organ donation and transplantation. Tight glycaemic control has been extensively studied in critical care over the past 15 years; however, this has not yet translated into the field of transplantation, where patients are more unwell and where improved outcomes remain an ongoing challenge. Insulin therapy and optimization of glycaemic control represent important areas for future hypothesis-driven research into organ donation and transplantation, such as amelioration of ischaemia-reperfusion injury, rejection and infection.

Published
2019
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7. Critical care scientists: Role, training and future directions

Author

Claire Jennings, Natalie Fowler, Raashid Ali, Stephen Playfor, Jonathan Bannard-Smith, and Michal Pruski

Subjects
Medical education, business.industry, education, Critical Care and Intensive Care Medicine, Critical Care Nursing, Allied health professions, 030226 pharmacology & pharmacy, Training (civil), humanities, 03 medical and health sciences, Special Article, 0302 clinical medicine, Medicine, 030212 general & internal medicine, business, health care economics and organizations
Abstract

Critical care scientists are a little known but increasingly prominent group of professionals, included in both the government-run Modernising Scientific Careers initiative and 2019 Guidelines for the Provision of Intensive Care Services. This article outlines the role of critical care scientists, their training programme and potential future directions for the role. A wider appreciation and acknowledgement of the critical care scientist’s role within the multi-disciplinary team will allow critical care units to fully understand the potential benefits that may be brought to patient care and service delivery.

Published
2021
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8. Detection and quantification of exhaled volatile organic compounds in mechanically ventilated patients-comparison of two sampling methods

Author

Iain R. White, Jonathan Bannard-Smith, Waqar Ahmed, Craig F. Johnson, Stephen J. Fowler, Pouline M.P. van Oort, Timothy Felton, Royston Goodacre, Lieuwe D. J. Bos, Paul Dark, Pulmonary medicine, Intensive Care Medicine, Pulmonology, ACS - Heart failure & arrhythmias, and AII - Inflammatory diseases

Subjects
medicine.medical_treatment, Suction catheter, 01 natural sciences, Biochemistry, Gas Chromatography-Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, Electrochemistry, medicine, Environmental Chemistry, Humans, Volatile organic compound, Spectroscopy, Mechanical ventilation, chemistry.chemical_classification, Volatile Organic Compounds, Chromatography, 010401 analytical chemistry, Breath sampling, Sampling (statistics), Exhalation, Respiration, Artificial, 0104 chemical sciences, 030228 respiratory system, chemistry, Breath gas analysis, Breath Tests, Environmental science, Respiratory equipment
Abstract

Exhaled breath analysis is a promising new diagnostic tool, but currently no standardised method for sampling is available in mechanically ventilated patients. We compared two breath sampling methods, first using an artificial ventilator circuit, then in "real life"in mechanically ventilated patients on the intensive care unit. In the laboratory circuit, a 24-component synthetic-breath volatile organic compound (VOC) mixture was injected into the system as air was sampled: (A) through a port on the exhalation limb of the circuit and (B) through a closed endo-bronchial suction catheter. Sorbent tubes were used to collect samples for analysis by thermal desorption-gas chromatography-mass spectrometry. Realistic mechanical ventilation rates and breath pressure-volume loops were established and method detection limits (MDLs) were calculated for all VOCs. Higher yields of VOCs were retrieved using the closed suction catheter; however, for several VOCs MDLs were compromised due to the background signal associated with plastic and rubber components in the catheters. Different brands of suction catheter were compared. Exhaled VOC data from 40 patient samples collected at two sites were then used to calculate the proportion of data analysed above the MDL. The relative performance of the two methods differed depending on the VOC under study and both methods showed sensitivity towards different exhaled VOCs. Furthermore, method performance differed depending on recruitment site, as the centres were equipped with different brands of respiratory equipment, an important consideration for the design of multicentre studies investigating exhaled VOCs in mechanically ventilated patients.

Published
2021
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9. Albumin as a drug: its biological effects beyond volume expansion

Author

Shailesh, Bihari, Jonathan, Bannard-Smith, and Rinaldo, Bellomo

Subjects
Albumins, Endothelial Cells, Homeostasis, Humans, Endothelium, Vascular, Glycocalyx
Abstract

Albumin is the most abundant and perhaps most important protein in human blood. Research has identified many of albumin's possible roles in modulating acid-base balance, modifying inflammation, maintaining vascular endothelial integrity, and binding endogenous and exogenous compounds. Albumin plays a key role in the homeostasis of vascular endothelium, offering protection from inflammation and damage to the glycocalyx. Albumin binds a diverse range of compounds. It transports, delivers and clears drugs, plus it helps with uptake, storage and disposal of potentially harmful biological products. The biological effects of albumin in critical illness are incompletely understood, but may enhance its clinical role beyond use as an intravenous fluid. In this article, we summarise the evidence surrounding albumin's biological and physiological effects beyond its use for plasma volume expansion, and explore potential mechanistic effects of albumin as a disease modifier in patients with critical illness.

Published
2020

10. More research is required to understand factors influencing antibiotic prescribing in complex conditions like suspected ventilator-associated pneumonia

Author

Christopher Bassford, Tina Van Den Broeck, Gert Boschman, Bryan Yates, A. John Simpson, Vanessa Linnett, Niall Anderson, Daniel F. McAuley, Jonathan Hulme, Jennie Parker, Cecilia M O'Kane, Gavin D. Perkins, Julian Sonksen, Anthony J. Rostron, Glenn Phair, Ashley Agus, Bronagh Blackwood, Suveer Singh, Lydia M Emerson, Kallirroi Kefala, D W James Keenan, Alistair I Roy, Ronan McMullan, Shondipon Laha, Timothy S. Walsh, Stephen Bonner, Nicole M Robin, Simon Baudouin, Paul Dark, Susan A Bowett, Ingeborg Welters, Ross L Paterson, Craig Spencer, Jonathan Scott, A Joy Allen, Jonathan Bannard-Smith, Thomas P Hellyer, Andrew Conway Morris, and Stephen E Wright

Subjects
RM, medicine.medical_specialty, Science & Technology, LAVAGE, business.industry, Ventilator-associated pneumonia, MEDLINE, General Medicine, Research & Experimental Medicine, medicine.disease, Antibiotic prescribing, Oncology, Medicine, Research & Experimental, medicine, Intensive care medicine, business, Life Sciences & Biomedicine, Letter to the Editor, RC
Published
2020
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11. Correction to: Challenges of one-year longitudinal follow-up of a prospective, observational cohort study using an anonymised database: recommendations for trainee research collaboratives

Author

Owen Thorpe, Muhamed Farhan-Alanie, DEVENDER MITTAPALLI, Aditya Borakati, Christopher Graham, Vinci Naruka, Shaikh Sanjid Seraj, Emily Greenan, Hannah Charlotte Copley, Shyam Gokani, Thomas Pinkney, Liam Cato, Sameera A, Edward Balai, Timothy Shao Ern Tan, Sogha Khawari, Joshua Burke, James Glasbey, Jonathan Bannard-Smith, Catrin Morgan, Paul Glen, Laurie Rigueros Springford, Claire Donohoe, Tom Abbott, Kenneth A McLean, Hew David Torrance, Gargi Samarth, Dalvir Bajwa, and Chung Shen Chean

Subjects
Male, lcsh:R5-920, Databases, Factual, Epidemiology, Data Collection, Correction, Health Informatics, Guidelines as Topic, Middle Aged, Education, Outcome Assessment, Health Care, Humans, Female, Longitudinal Studies, Prospective Studies, lcsh:Medicine (General), Digestive System Surgical Procedures, Aged, Follow-Up Studies
Abstract

Trainee research collaboratives (TRCs) have pioneered high quality, prospective 'snap-shot' surgical cohort studies in the UK. Outcomes After Kidney injury in Surgery (OAKS) was the first TRC cohort study to attempt to collect one-year follow-up data. The aims of this study were to evaluate one-year follow-up and data completion rates, and to identify factors associated with improved follow-up rates.In this multicentre study, patients undergoing major gastrointestinal surgery were prospectively identified and followed up at one-year following surgery for six clinical outcomes. The primary outcome for this report was the follow-up rate for mortality at 1 year. The secondary outcome was the data completeness rate in those patients who were followed-up. An electronic survey was disseminated to investigators to identify strategies associated with improved follow-up.Of the 173 centres that collected baseline data, 126 centres registered to participate in one-year follow-up. Overall 62.3% (3482/5585) of patients were followed-up at 1 year; in centres registered to collect one-year outcomes, the follow-up rate was 82.6% (3482/4213). There were no differences in sex, comorbidity, operative urgency, or 7-day postoperative AKI rate between patients who were lost to follow-up and those who were successfully followed-up. In centres registered to collect one-year follow-up outcomes, overall data completeness was 83.1%, with 57.9% (73/126) of centres having ≥95% data completeness. Factors associated with increased likelihood of achieving ≥95% data completeness were total number of patients to be followed-up (77.4% in centres with 15 patients, 59.0% with 15-29 patients, 51.4% with 30-59 patients, and 36.8% with 60 patients, p = 0.030), and central versus local storage of patient identifiers (72.5% vs 48.0%, respectively, p = 0.006).TRC methodology can be used to follow-up patients identified in prospective cohort studies at one-year. Follow-up rates are maximized by central storage of patient identifiers.

Published
2020

12. Understanding antimicrobial prescribing in suspected ventilator-associated pneumonia: a prospective cohort study

Author

Yun Xu, Callum Docherty, Stephen A Roberts, Roy Goodacre, Ingeborg Walters, Ben Morton, Stephen J. Fowler, Jonathan Bannard-Smith, Paul Dark, Timothy Felton, Ronan McMullan, and Iain R White

Subjects
medicine.medical_specialty, APACHE II, business.industry, Ventilator-associated pneumonia, Odds ratio, medicine.disease, Antimicrobial, respiratory tract diseases, Pneumonia, Internal medicine, Intensive care, Medicine, General Materials Science, Clinical significance, business, Prospective cohort study
Abstract

Background Ventilator-associated pneumonia (VAP) is associated with significant healthcare cost, morbidity, and mortality, but can be difficult to identify, resulting in over-diagnosis and excessive use of broad-spectrum antimicrobial therapy. In addition, some organisms commonly cultured from the airways of critically ill patients, in particular Candida species, are of unknown clinical significance. Methods A prospective cohort study was conducted across five intensive care units in the North-West of England. Participants were enrolled within 24 hours of commencing antimicrobial therapy for suspected VAP. Laboratory-confirmed VAP was defined by quantitative culture of a known pneumonia-causing pathogen above predetermined growth thresholds. Univariate logistic regression was used to determine the impact of laboratory-confirmed VAP, APACHE II, culture of Staphylococcus aureus, and culture of Candida species on 30-day mortality. Results The prevalence of laboratory-confirmed VAP was 43/96 (44%), and the median number of antimicrobials prescribed for VAP was 1 (range: 1-4). Candida species were identified in 32/96 patients (33%). The overall 30-day mortality was 22/96 (26%). None of the variables analysed were associated with 30-day mortality, except for culture of Candida species, which was associated with survival (odds ratio 0.26, 95% CI 0.07 to 0.98; p= 0.047). Conclusions Ventilator-associated pneumonia was confirmed in under half the patients commenced on antimicrobial therapy for suspected VAP, which highlights the urgent need for improved diagnostic strategies. In our clinical practice, Candida species are not treated as pathogenic in VAP, and in this study, growth of Candida species was not associated with excess 30-day mortality.

Published
2020
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13. Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study

Author

Rahul Bhome, Teo Lopez Bernal, Owen Thorpe, Conor Keogh, Raiyyan Aftab, Muhamed Farhan-Alanie, DEVENDER MITTAPALLI, Aditya Borakati, Roshni Bhudia, Christopher Graham, Vinci Naruka, Dermot Burke, Nicholas Wroe, James Fitzgerald, Matthew Hague, Shaikh Sanjid Seraj, Katie Dunleavy, Emily Greenan, Samira Bell, Hannah Charlotte Copley, Clementina Calabria, Daniel Ahern, Abdul-Rahman Gomaa, Joseph Yates, Chetan Khatri, Martin Connor, Thomas Robert William Ward, Shyam Gokani, Thomas Pinkney, Liam Cato, Edward Balai, Timothy Shao Ern Tan, Sogha Khawari, Peter Coe, Stephen Robinson, STARSurg Collaborative, Joshua Burke, Melika Akhbari, James Glasbey, Nida Ahmed, Jonathan Bannard-Smith, Catrin Morgan, Paul Glen, Laurie Rigueros Springford, Claire Donohoe, Heather Davis, Richard Bogle, Elizabeth Wootton, Mehnoor Khaliq, Sam Myers, Alex Elizabeth Ward, Joanna Osmanska, Jacob King, Oliver Warren, Martin Whyte, Renol M Koshy, Joseph Meredith, Harry VM Spiers, Thomas Ashdown, John Hayes, Hew David Torrance, Dalvir Bajwa, Emanuele Gammeri, Rebecca Spencer, Adam Gwozdz, Kirtan Patel, Jaspreet Kaur Seehra, and Chung Shen Chean

Subjects
medicine.medical_specialty, Surgical stress, business.industry, Mortality rate, Acute kidney injury, Renal function, General Medicine, Odds ratio, medicine.disease, Preoperative care, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, 030212 general & internal medicine, Stage (cooking), business, Cohort study
Abstract

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability.

Published
2018
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14. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure

Author

Tamas Szakmany, Ashley Agus, Redmond P Tully, Michael A. Gillies, Gavin D. Perkins, William Tunnicliffe, Jonathan Bannard-Smith, Daniel Brodie, David A Harrison, Daniel F. McAuley, Andrew J. Boyle, Duncan Young, Cliona McDowell, Andrew Bentley, Nicholas A Barrett, James J. McNamee, Colette Jackson, and Jonathan E Millar

Subjects
Male, Extracorporeal Circulation, Respiratory Insufficiency/mortality, medicine.medical_treatment, Kaplan-Meier Estimate, law.invention, Carbon Dioxide/blood, Randomized controlled trial, law, Intensive care, Extracorporeal Circulation/adverse effects, Tidal Volume, Humans, Medicine, Tidal volume, Aged, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Extracorporeal circulation, Environmental air flow, Respiratory Distress Syndrome/therapy, General Medicine, Carbon Dioxide, Middle Aged, Respiration, Artificial/adverse effects, Respiration, Artificial, Anesthesia, Relative risk, Early Termination of Clinical Trials, Breathing, Female, Respiratory Insufficiency, business
Abstract

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes.Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure.Design, Setting, and Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020.Interventions: Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210).Main Outcomes and Measures: The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates.Results: Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device.Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference.Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.

Published
2021
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15. Students' participation in collaborative research should be recognised

Author

Aditya Borakati, Kenneth McLean, Thomas M. Drake, Ewen M. Harrison, Sivesh K. Kamarajah, Chetan Khatri, Dmitri Nepogodiev, Minaam Abbas, Muhammad Abdalkoddus, Areej Abdel-Fattah, Reem Abdelgalil, Haweya Abdikadir, Ryan Adams, Sarah Adams, Inioluwa Adelaja, Abiola Adeogun, Helena Adjei, Amirul Adlan, Hussamuddin Adwan, Sara Aeyad, Raiyyan Aftab, Amir Afzul, Vani Agarwal, Hosam Aglan, Medha Agrawal, Rishi Agrawal, Fiza Ahmed, Sobia Akhtar, Onyinye Akpenyi, Maithem Al-Attar, Muhammed Al-Ausi, Waleed Al-Khyatt, Alia Al-Mousawi, Zainab Al-Nasser, Anand Alagappan, Justin Alberts, Maryam Alfa-Wali, Abdulmajid Ali, Adnan Ali, Tamara Ali, Bilal Alkhaffaf, Rachael Allen, Kassem Alubaidi, Edemanwan Andah, Richard Anderson, Kirstine Andrew, Andrew Ang, Eshen Ang, Theophilus Anyomih, James Archer, Matt Archer, Steven Arnell, Matthew Arnold, Esha Arora, Nadeem Ashraf, Raees Ashraf, Jordan Ashwood, Usama Asif, Andrew Atayi, Sameera Auckburally, Ralph Austin, Sultana Azam, Aishah Azri Yahaya, Fiyin Babatunde, Simon Bach, Roudi Bachar, Abdul Badran, Caroline Baillie, Edward Balai, Alexander Baldwin, Vartan Balian, Danielle Banfield, Jonathan Bannard-Smith, Connor Barker, Behrad Barmayehvar, Jane Barnfield, David Bartlett, Richard Bartlett, Kwaku Baryeh, Siddharth Basetti, Kellie Bateman, Michael Bath, Andrew Beamish, William Beasley, Simon Beecroft, Ardit Begaj, Gurpreet Beghal, Jessica Belchos, Katarzyna Bera, Tara Bergara, Anna Betts, Aneel Bhangu, Gayathri Bhaskaran, Amina Bhatti, Mihai Bica, Caitlin Billyard, Emily Birkin, Jane Blazeby, Harry Blege, Natalie Blencowe, Christopher Blore, Alex Boddy, Matthew Boissaud-Cooke, Anita Bolina, William Bolton, David Bosanquet, Doug Bowley, Kathryn Boyce, Graham Branagan, Jessica Brayley, Joanna Brecher, Kristina Bresges, Emily Briggs, Ryan Broll, Damien Brown, Elliot Brown, Leo Brown, Robin Brown, Rory Brown, Connor Bruce, Pepa Bruce, Rory Buckle, Emily Budd, Richard Buka, Dermot Burke, Joshua Burke, Alisha Burman, Laura Burney, Amy Burrows, Mohammed Bux, Ronan Cahill, Clementina Calabria, Julian Camilleri-Brennan, Amy Campbell, Bill Campbell, Matthew Cant, Yun Cao, Sophie Carlson, Grace Carr, Luke Carr, Rebecca Carr, Richard Carr, Eleanor Cartwright, Alice Castle, Kirsty Cattle, Daniel Cave, Stephen Chapman, Alexandros Charalabopoulos, Sanjay Chaudhri, Ahmad Chaudhry, Paresh Chauhan, Priyesh Chauhan, Ryad Chebbout, Yunzi Chen, Louisa Chenciner, Jingjie Cheng, Natalie Cheng, Lin Chew, Zenab China, Abhishek Chitnis, Praminthra Chitsabesan, Paul Choi, Sarah Choi, Mariam Choudhry, Chern Choy, Claudia Ciurleo, Henry Claireaux, Peter Coe, Simon Cole, Katy Concannon, Edward Cope, Olivia Corbridge, Jessica Court, Louise Cox, Anna Craig-Mcquaide, Ben Cresswell, Lauren Crozier, Neil Cruickshank, Lucy Cuckow, Helen Cui, Elspeth Cumber, Sarah Cumming, Olivia Cundy, Melissa Cunha, Pedro Cunha, Laura Cunliffe, Jazleen Dada, Prita Daliya, Jeffrey Dalli, Ian Daniels, James Daniels, Ahmed Daoub, Sabeera Dar, Emma Das, Kaustuv Das, Emily Davies, Gareth Davies, Kirsty Davies, Kristen Davies, Rachel Davies, Victoria Dawe, Joshua Lucas de Carvalho, Katie De Jong, Katherine Deasy, Praveena Deekonda, Sahil Deepak, Henal Desai, Karishma Desai, Ryan Devlin, Nishat Dewan, Akashdeep Dhillon, Priya Dhillon, Tanya Dhir, Salomone Di Saverio, Julia Diamond, Peter Dib, Panagiotis A. Dimitriadis, Shiva Dindyal, Matthew Doe, Ciaran Doehrty, Tara Dogra, Arpan Doshi, Alison Downey, Joseph Doyle, Ashleigh Draper, Sarah Duff, Joseph Duncumb, Sophie Dupre, Justine Durno, Michal Dzieweczynski, Nicola Eardley, Sarah Easby, Sam Easdon, Hamdi Ebdewi, Lydon Eccles, Jacob Edwards, Padma Eedarapalli, Mohamed Elbuzidi, Patrick Elder, Lucy Elliott, Malaz Elsaddig, Ysabelle Embury-Young, Sophie Emesih, Alec Engledow, William English, Christos Episkopos, Jonathan Epstein, Rahim Esmail, Taher Fatayer, Nicolò Favero, Nicola Fearnhead, Maxine Feldman, Evelyn Fennelly, Stephen Fenwick, Lucie Ferguson, Stuart Fergusson, Petros Fessas, Isabel FitzGerald, J. Edward Fitzgerald, Harry Fitzpatrick, Daniel Fletcher, Tonia Forjoe, Beniamino Forte, Alex Fowler, Benjamin France, Abraham Francis, Niroshan Francis, Sunil Francis, Sam Freeman, Vicky Fretwell, Teresa Fung, Hugh Furness, Michael Gallagher, Stuart Gallagher, Chuanyu Gao, Lothaire Garard, Shona Gardner, Andrew Gaukroger, Daniel George, Simi George, Jamal Ghaddar, Ali Ghaffar, Shamira Ghouse, Amanda Gilbert, Ashveen Gill, Francesco Giovinazzo, Carey Girling, Lolade Giwa, James Glasbey, Paul Glen, Mary Goble, Jenna Godfrey, Shreya Goel, Wenn Goh, Kajal Gohil, Shyam Gokani, David Gold, David Golding, Andrea Gonzalez-Ciscar, Ross Goodson, Melissa Gough, Shubhangi Govil, Thomas Gower, Christopher Graham, Sam Gray, Patrick Green, Samuel Greenhalgh, Kyriacos Gregoriou, Rhiannon Gribbell, Mary Catherine Gribbon, Charlotte Grieco, Emma Griffiths, Ewen Griffiths, Nathan Griffiths, Sara Griffiths, Cathleen Grossart, Daniel Guerero, Christianne Guillotte, Rishi Gupta, Claire Guy, Adam Gwozdz, James Haddow, Shazia Hafiz, Constantine Halkias, Elisabeth Hall, Hasseb Hamid, Emma Hamilton, Gurvinder Singh Harbhajan Singh, John Hardman, Rhiannon Harries, Rhydian Harris, Suzanne Harrogate, Megan Harty, Jessica Harvey, Rahima Hashemi, Ahmed Hassane, Helen Hawkins, Thomas Hawthorne, John Hayes, Phoebe Hazenberg, Harry Heath, Madhusoodhana Hebbar, R. Heer, Roisin Hegarty O'Dowd, David Henshall, Philip Herrod, Elizabeth Hester, Emily Heywood, Nick Heywood, Frances Hill, James Hill, Kirsty Hill, May Ho, Marianne Hollyman, David Holroyd, Joseph Home, Steve Hornby, Laura Horne, Charlotte Horseman, Huma Hosamuddin, Amy Hough, George Hourston, Nathan Hudson-Peacock, Belinda Hughes, Katie Hughes, Isabel Huppatz, Penelope Hurst, Mahrukh Hussain, Shoaib Fahad Hussain, Syeda Hussain, Imogen Hutchings, Bilal Ibrahim, Lema Imam, Rory Ingham, Rose Ingleton, Rizwan Iqbal, Jenny Isherwood, Abdurrahman Islim, Omar Ismail, Shashank Iyer, Toby Jackman, Prashant Jain, Nadeem Jamal, Sabine Jamal, Ellen James, Nirmitha Jayaratne, Nathan Jeffreys, Hiral Jhala, Courtney Johnson, Zoe Johnston, Conor Jones, Emma-Jane Jones, Keaton Jones, Victor Jones, Roshan Joseph, Dilan Joshi, Holly Joyce, Claire Joyner, Aditya Kale, Sagar Kanabar, Lina Kanapeckaite, Hadyn Kankam, Sarantos Kaptanis, Edward Karam, Dimitrios Karponis, Anne Karunatilleke, Veeru Kasivisvanathan, Geeta Kaur, Samina Kauser, Nigel Keelty, Denise Kelly, Jessica Kennett, Molly Kerr, Ahmed Kerwan, Apoorva Khajuria, Mostafa Khalil, Mehnoor Khaliq, Ayushah Khan, Hamzah Khan, Haroon Khan, Maaz Khan, Maria Khan, Shahab Khan, Kaywaan Khan, Rachel Khaw, Ashni Kheterpal, Parisa Khonsari, Miraen Kiandee, Samuel Kim, Suji Kim, Sung-Hee Kim, Harry King, Anna Kinsella, Ajit Kishore, Stefan Klimach, Angelos G. Kolias, Anna Kolodziejczyk, Chia Yew Kong, Tseun Han James Kong, Omar Kouli, Sebi Kukran, Sevi Kukran, Geev Kumaran, Vladislav Kutuzov, Chris Laing, Georgina Laing, Kulvinder Lal, Peter Lalor, Joel Lambert, Sai Geethan Lambotharan, Eve Lancaster, Jasmine Latter, Michelle Latter, Kenny Lau, Alexa Lazarou, Madeline Leadon, Gabriel Lee, Jeyoung Lee, Kathryn Lee, Matthew Lee, Samuel Lee, Zong Lee, Edward Leung, Thomas Lewis, Hansen Li, Mimi Li, Wan Jane Liew, Yao Ren Liew, Alexander Light, Lydia Lilis, Diana Lim, Hui Lim, Joseph Lim, Zhi Lim, Siyin Liu, James Lloyd, Andrew Logan, Priya Loganathan, M. Long, Lydia Longstaff, Luisa Lopez Rojas, Richard Lovegrove, Jack Lowe-Zinola, Byron Lu Morrell, Joshua Luck, Andreas Luhmann, Surabhika Lunawat, Jon Lund, Cong Luo, Lorna Luo, Iona Lyell, Panagis Lykoudis, Jonathan Macdonald, Aliya Mackenzie, Conor Magee, Pooja Mahankali-Rao, Kamal Mahawar, Mehreen Mahfooz, Faisal Mahmood, Samir Makwana, Tom Malik, Sohaib Mallick, Jyothis Manalayil, Tinaye Mandishona, Sudhakar Mangam, Maniragav Manimaran, Natarajan Manimaran, Chris Manson, Sufyan Mansoor, Fatima Mansour, Alejandro Marcos Rodrigo, Nicholas Markham, Maria Marks, Paul Marriott, Hannah Marsden, Laura Martin, Tiago Martins, John Mason, Luke Mason, Mariam Masood, Nikhil Math, Ginimol Mathew, Jacob Matthews, Jonathan Mayes, Ursula Mc Gee, Ross Mcallister, Sandra Mcallister, Scott Mccain, Conor Mccann, Emmet Mccann, Cathal McCarthy, Gillian Mccoll, Greg Mcconaghie, Ace Mcdermott, Frank McDermott, Rachel Mcdougall, Mark McDowell, Gordon McFarlane, Richard McGregor, Doug McKechnie, Jillian McKenna, Scott McKinstry, Georgia Mclachlan, E. Mclean, Elizabeth McLennan, Angus McNair, Kenneth Mealy, Lauren Mecia, Alexander Mehta, Aidan Mellan, Arathi Menon, Donald Menzies, Zhubene Mesbah, David Messenger, George Miller, Aseem Mishra, Sona Mistry, Tahira Mohamed, Nisha Mohamed Mushaini, Midhun Mohan, Ameerah Mohd Azmilssss, Ajay Mohite, Krishna Moorthy, Jalal Moradzadeh, Richard Morgan, Gabriella Morley, Alice Mortimer, Hannah Mownah, Paul Moxey, Gagira Mudalige, Umarah Muhammad, Samuel Munday, Ben Murphy, Ciaran Murphy, Caoimhe Murray, Hannah Murray, Michael Murray, Mohammed Ibrar Murtaza, Jameel Mushtaq, Ameer Mustafa, Shams Mustafa, Laura Myers, Sam Myers, Adeeb Naasan, Kiran Nadeem, Hanzla Naeem, Prashant Naik, Arun Nair, Keshav K. Nambiar, Muhammad Naqi, Zehra Naqvi, Yan Ning Neo, Georgia Irene Neophytou, Jonathan Neville, Tom Newman, Benjamin Ng, Guat Ng, Jing Qi Ng, Vincent Ng, Zhan Herr Ng, Maire Ni Bhoirne, James Nicholas, Gary Nicholson, George Ninkovic-Hall, Gemma Nixon, Mike Norwood, Toby Noton, Romman Nourzaie, Richard Novell, Donald Nyanhongo, James O'Brien, Rory O'Kane, Stephen O'Neill, Hugh O'Sullivan, Thomas Oakley, Chinomso Ogbuokiri, Oluwafunto Ogunleye, Su Oh, Emezie Okorocha, James Olivier, Rele Ologunde, Sharif Omara, Alice Ormrod, Caroline Osborne, Joanna Osmanska, Raisah Owasil, Sebastian Owczarek, Ezgi Ozcan, Sri Palaniappan, Francesco Palazzo, Abbas Palkhi, Gargi Pandey, James Park, Jennifer Parker, Anna Parry, James Parsonage, Lauren Passby, Bhavi Patel, Bhavik Patel, Chantal Patel, Dinisha Patel, Kirtan Patel, Panna Patel, Pratiksha Patel, Trupesh Patel, Mariasoosai Pathmarajah, Amogh Patil, Pradeep Patil, Yusuf Patrick, Jessica Pearce, Lyndsay Pearce, Colin Peirce, Bryony Peiris, Amy Pendrill, Sreelata Periketi, Michael Perry, George Petrov, Charlotte Phillips, Grace Pike, Ana Catarina Pinho-Gomes, Parhana Polly, Arachchige Ponweera, Yanish Poolovadoo, Raunak Poonawala, Petya Popova, Dimitri Pournaras, Brooke Powell, Praveena Prabakaran, Esha Prakash, Tapani Pratumsuwan, Anusha Prem Kumar, Helen Puddy, Michael Pullinger, Nikita Punjabi, Oliver Charles Putt, Omar Qadir, Mubasher Qamar, Patrick Quinn, Arham Qureshi, Mohamed Rabie, Angus Radford, Anand Radhakrishnan, Ansh Radotra, Nasir Rafiq, Aria Rahem, Nahim Rahman, Syed Rahman, Ramesh Rajagopal, Nick Rajan, Nikitha Rajaraman, Sumetha Rajendran, Liandra Ramachenderam, Divya Ramakrishnan, Denisha Ramjas, James Rammell, Ritika Rampal, George Ramsay, Ratan Randhawa, Ellis Rea, Stephanie Rees, Saad Rehman, Salwah Rehman, Nabila Rehnnuma, Melina Rejayee, Zakaria Rob, Charlotte Roberts, Grace Roberts, Ben Roberts, Harry Robinson, Stephen Robinson, Ailin Rogers, Alex Rogers, William Rook, Talisa Ross, Chloe Roy, Azelea Rushd, Duncan Rutherford, Michael Saat, Kaushik Sadanand, Rebecca Sagar, Harkiran Sagoo, Arin Saha, Kapil Sahnan, Mohammed Salik Sait, Saif Sait, Damien Salekin, Mostafa Salem, Nadia Salloum, Emma Sanders, Jasmesh Sandhu, N. Sandhu, Lorna Sandison, Laura Sandland-Taylor, Ron Sangal, Chandan Sanghera, Josephine Saramunda, Lauren Satterthwaite, Moritz Schramm, Rupert Scott, Chloe Searle, Harkiran Seehra, Juan Jose Segura-Sampedro, Harpreet Kaur Sekhon Inderjit Singh, Shaikh Sanjid Seraj, Ishani Seth, Rajiv Sethi, Apar Shah, Mario Shaid, Shafaque Shaikh, Awad Shamali, Elizabeth Sharkey, Abhi Sharma, Neil Sharma, Sachin Sharma, Aniruddh Shenoy, Maleasha Shergill, Shahram Shirazi, Imran Siddiqui, Raykal Sim, Lucy Simmonds, Andrew Simon, William Simpson, Bharpoor Singh, J. Singh, Prashant Singh, Anant Sinha, Sidhartha Sinha, Robert Sinnerton, Chaamanti Sivakumar, Brendan Skelly, Richard Slater, Samuel Small, Neil Smart, Yat Wing Smart, Alexander Smith, Charlotte Smith, Jason Smith, Rebecca Smith, Scott Smith, Peter Sodde, Zhi Min Soh, Aniket Sonsale, Ahmed Soualhi, John Spearman, Robert Spencer, Harry Spiers, Philip Stather, Michael Stoddart, Bradley Storey, Howard Stringer, Thomas Stringfellow, Ben Stubbs, Niv Sukir, Nivian Sukirthan, Yasir Suleman, Aparnah Sureshkumar, Ashwin Suri, Timen Swartbol, Hyder Tahir, E. Tian Tan, Huai Ling Tan, Laura Tan, Alethea Tang, Priyal Taribagil, Yao Zong Tay, Beth Taylor, Zara Taylor, Alexandra Thatcher, Rachel Thavayogan, Michael Thomaa, Daniah Thomas, Jenny Thomas, Paul Thomas, Thomas Pinkney, Chris Thompson, Mag Ting, Ethan Toner, Godwin Tong, Jared Torkington, Molly Traish, Miles Triniman, John Trotter, Kwong Tsang, Sanchit Turaga, Hannah Turley, James Turner, Tomas Urbonas, Alexandra Urquhart, Nimai Vadgama, Aashay Vaidya, Gijs van Boxel, Swati Vara, Massimo Varcada, Rebecca Varley, Dee Varma, Martinique Vella-Baldacchino, Sara Venturini, Naina Verma, Saurabh Verma, Gabrielle Vernet, Mark Vipond, Alex von Roon, Qasim Wadood, Kathryn Waite, Lewis Walker, Nathan Walker, Jonathan C.M. Wan, Liyang Wang, Xue Wang, Alex Ward, Thomas Ward, Nienke Warnaar, Lloyd Warren, Oliver Warren, Sam Waters, Angus Watson, Laura Jayne Watson, Dominic Waugh, Daniel Weinberg, Malcolm West, Carla White, Tim White, Katharine Whitehurst, Robert Whitham, Tharindri Wijekoon, Manuk Wijeyaratne, Richard Wilkin, Alex Wilkins, Adam Williams, Gethin Williams, Luke Williams, Robert Williams, Andrew Williamson, Jacinthe Willson, Andrew Wilson, Holly Wilson, James Wilson, Lizzie Wilson, Megan Wilson, Michael Wilson, Rebekah Wilson, Tim Wilson, Evelina Woin, Esther Wright, Jenny Wright, Nicholas Wroe, Joanne Wylie, Yiwang Xu, Satheesh Yalamarthi, Angela Yan, Narisu Yang, Eda Yardimci, Ibrahim Yasin, Ismael Yasin, Noor Yasin, Joseph Yates, Jih Dar Yau, Tricia Yeoh, Joshua Yip, Cissy Yong, Vasudev Zaver, Tatiana Zhelezniakova, and Adreana Zulkifli

Subjects
Medical education, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, MEDLINE, General Medicine, 030230 surgery, Collaborative research, 03 medical and health sciences, 0302 clinical medicine, Foundation Programme, Medicine, Surgery, 030212 general & internal medicine, business
Published
2017
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16. Challenges of one-year longitudinal follow-up of a prospective, observational cohort study using an anonymised database: recommendations for trainee research collaboratives

Author

Rahul Bhome, Mohamad Hussain, Owen Thorpe, Conor Keogh, Muhamed Farhan-Alanie, DEVENDER MITTAPALLI, Aditya Borakati, Christopher Graham, Vinci Naruka, Moritz Schramm, Prasanna Partha Sarathy, Kritchai Vutipongsatorn, Souradip Mookerjee, James Fitzgerald, Matthew Hague, Shaikh Sanjid Seraj, Emily Greenan, Samira Bell, Abdul Badran, Hannah Charlotte Copley, Clementina Calabria, Bradley Storey, Abdul-Rahman Gomaa, Dimitrios Karponis, Fraser Peck, Wen Jie Koay, Shyam Gokani, Thomas Pinkney, Luke McMenamin, Liam Cato, Sameera A, Eve Robertson, Edward Balai, Timothy Shao Ern Tan, Jonathan Lund, Peter Coe, Stephen Robinson, STARSurg Collaborative, Joshua Burke, Melika Akhbari, James Glasbey, Jonathan Bannard-Smith, Catrin Morgan, Ewen Harrison, Paul Glen, Claire Donohoe, Heather Davis, Richard Bogle, Tom Abbott, Emily Mills, Mehnoor Khaliq, Alex Elizabeth Ward, Sivesh K Kamarajah, Joanna Osmanska, Stefano Capella, Stephen O'Neill, Harry VM Spiers, Scott Smith, Kenneth A McLean, SOO KUN LIM, Thomas Ashdown, John Hayes, Gargi Samarth, Dalvir Bajwa, John Hardie, Adnan Ali, Emanuele Gammeri, Roudi Bachar, Jaspreet Kaur Seehra, and Chung Shen Chean

Subjects
medicine.medical_specialty, Epidemiology, IMPACT, MEDLINE, MULTICENTER, ACUTE KIDNEY INJURY, Health Informatics, SURGICAL RESEARCH, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, Secondary outcome, Primary outcome, General & Internal Medicine, medicine, Kidney injury, 030212 general & internal medicine, Prospective cohort study, lcsh:R5-920, Science & Technology, STARSurg Collaborative, business.industry, MORTALITY, Follow-up, Methodology, Baseline data, medicine.disease, Research collaborative, Comorbidity, Health Care Sciences & Services, 030220 oncology & carcinogenesis, Emergency medicine, Surgery, business, lcsh:Medicine (General), Life Sciences & Biomedicine, Cohort study, Research Article
Abstract

Background Trainee research collaboratives (TRCs) have pioneered high quality, prospective ‘snap-shot’ surgical cohort studies in the UK. Outcomes After Kidney injury in Surgery (OAKS) was the first TRC cohort study to attempt to collect one-year follow-up data. The aims of this study were to evaluate one-year follow-up and data completion rates, and to identify factors associated with improved follow-up rates. Methods In this multicentre study, patients undergoing major gastrointestinal surgery were prospectively identified and followed up at one-year following surgery for six clinical outcomes. The primary outcome for this report was the follow-up rate for mortality at 1 year. The secondary outcome was the data completeness rate in those patients who were followed-up. An electronic survey was disseminated to investigators to identify strategies associated with improved follow-up. Results Of the 173 centres that collected baseline data, 126 centres registered to participate in one-year follow-up. Overall 62.3% (3482/5585) of patients were followed-up at 1 year; in centres registered to collect one-year outcomes, the follow-up rate was 82.6% (3482/4213). There were no differences in sex, comorbidity, operative urgency, or 7-day postoperative AKI rate between patients who were lost to follow-up and those who were successfully followed-up. In centres registered to collect one-year follow-up outcomes, overall data completeness was 83.1%, with 57.9% (73/126) of centres having ≥95% data completeness. Factors associated with increased likelihood of achieving ≥95% data completeness were total number of patients to be followed-up (77.4% in centres with 60 patients, p = 0.030), and central versus local storage of patient identifiers (72.5% vs 48.0%, respectively, p = 0.006). Conclusions TRC methodology can be used to follow-up patients identified in prospective cohort studies at one-year. Follow-up rates are maximized by central storage of patient identifiers.

Published
2019
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17. Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation

Author

D W James Keenan, Alistair I Roy, Ronan McMullan, Ashley Agus, Niall Anderson, Gert Boschman, Christopher Bassford, Stephen E Wright, Jonathan Scott, Anthony J. Rostron, A. John Simpson, Nicole M Robin, Cecilia O'Kane, Vanessa Linnett, Simon Baudouin, Ingeborg Welters, Jonathan Hulme, Susan A Bowett, Glenn Phair, Lydia M Emerson, Daniel F. McAuley, A Joy Allen, Julian Sonksen, Bronagh Blackwood, Paul Dark, Ross L Paterson, Kallirroi Kefala, Stephen Bonner, Gavin D. Perkins, Bryan Yates, Tina Van Den Broeck, Jennie Parker, Shondipon Laha, Timothy S. Walsh, Craig Spencer, Thomas P Hellyer, Suveer Singh, Jonathan Bannard-Smith, and Andrew Conway Morris

Subjects
Male, Antibiotics, Respiratory System, Critical Care and Intensive Care Medicine, GUIDELINES, Bronchoalveolar Lavage, antibiotics, State Medicine, law.invention, RESPIRATORY-TRACT INFECTION, Antimicrobial Stewardship, 0302 clinical medicine, Bronchoscopy, Randomized controlled trial, law, 030212 general & internal medicine, medicine.diagnostic_test, Process Assessment, Health Care, Ventilator-associated pneumonia, Pneumonia, Ventilator-Associated, Middle Aged, Intensive care unit, INTENSIVE-CARE UNITS, PREVALENCE, Anti-Bacterial Agents, Editorial Commentary, biomarker, Female, Life Sciences & Biomedicine, Bronchoalveolar Lavage Fluid, Pulmonary and Respiratory Medicine, ventilator, RM, medicine.medical_specialty, STRATEGIES, medicine.drug_class, DIAGNOSIS, 1117 Public Health and Health Services, 03 medical and health sciences, Critical Care Medicine, Internal medicine, General & Internal Medicine, medicine, pneumonia, Humans, EXPOSURE, PROCALCITONIN, Contributions to Practice, Science & Technology, business.industry, MORTALITY, 1103 Clinical Sciences, medicine.disease, R1, United Kingdom, Pneumonia, Bronchoalveolar lavage, 030228 respiratory system, Clinical trials unit, ICU, VAP, business, RA, Biomarkers, RC, 1199 Other Medical and Health Sciences
Abstract

Background: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia.Methods: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425.Findings: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes.Interpretation: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect.Funding: UK Department of Health and the Wellcome Trust.

Published
2019
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18. Recovery from profound acidosis (pH 6.685) in multi-organ dysfunction syndrome

Author

Christopher Saleh, Eryl A Davies, and Jonathan Bannard-Smith

Subjects
medicine.medical_specialty, Multi organ dysfunction, business.industry, Feature (computer vision), medicine, Emergency department, Case Reports, medicine.symptom, Critical Care and Intensive Care Medicine, Critical Care Nursing, Intensive care medicine, business, Acidosis
Abstract

Acidosis is a common feature of patients referred to critical care from the emergency department. We present the case of a 49-year-old female with multi-organ dysfunction syndrome (MODS) and an arterial pH of 6.685 on arrival to the emergency department. This case is unique as the patient was in circulatory shock with MODS from rhabdomyolysis on arrival and had not suffered a cardiac arrest. We believe this to be the first reported case of full recovery from such an extreme metabolic disturbance in this context, and discuss the relevance of profound acidosis to early clinical decision-making.

Published
2019

19. Perioperative intravenous contrast administration and the incidence of acute kidney injury after major gastrointestinal surgery: prospective, multicentre cohort study

Author

Rahul Bhome, Prashant Patel, Owen Thorpe, Conor Keogh, Raiyyan Aftab, Muhamed Farhan-Alanie, DEVENDER MITTAPALLI, Matthew Chan, Aditya Borakati, Roshni Bhudia, Christopher Graham, Vinci Naruka, Moritz Schramm, Michael Kerin, Prasanna Partha Sarathy, Nicholas Wroe, Samian Sulaiman, Michael Stoddart, James Fitzgerald, Shaikh Sanjid Seraj, Katie Dunleavy, Emily Greenan, Samira Bell, Robert Whitham, Hannah Charlotte Copley, Clementina Calabria, Daniel Ahern, Abdul-Rahman Gomaa, Fraser Peck, Chetan Khatri, Janet Martin, Martin Connor, Thomas Robert William Ward, Waheed-Ul-Rahman Ahmed, Shyam Gokani, Thomas Pinkney, Camilla English, Liam Cato, Sameera A, Edward Balai, Timothy Shao Ern Tan, Sogha Khawari, Siew Yim Loh, Jonathan Lund, Peter Coe, Stephen Robinson, STARSurg Collaborative, Melika Akhbari, P. Ronan O'Connell, James Glasbey, Roshan Joseph, Jonathan Bannard-Smith, Catrin Morgan, Paul Glen, Laurie Rigueros Springford, Claire Donohoe, Heather Davis, Tom Abbott, Justine Davies, Mehnoor Khaliq, James Olivier, Sivesh K Kamarajah, Joanna Osmanska, Stefano Capella, Piriyankan Ananthavarathan, Stephen O'Neill, Oliver Warren, Clair Harris, Harry VM Spiers, Kenneth A McLean, SOO KUN LIM, Thomas Ashdown, John Hayes, Hew David Torrance, Dalvir Bajwa, Emanuele Gammeri, Adam Gwozdz, Hazem Hussein, Kirtan Patel, Jaspreet Kaur Seehra, Chung Shen Chean, and Aneel Bhangu

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Contrast Media, 030204 cardiovascular system & hematology, Preoperative care, Perioperative Care, 030218 nuclear medicine & medical imaging, Nephropathy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Postoperative Complications, medicine, Clinical endpoint, Odds Ratio, Humans, Prospective Studies, Prospective cohort study, Propensity Score, Digestive System Surgical Procedures, Aged, Aged, 80 and over, business.industry, Incidence, Acute kidney injury, Perioperative, Odds ratio, Acute Kidney Injury, Middle Aged, medicine.disease, Surgery, Female, business, Tomography, X-Ray Computed, Cohort study
Abstract

This study aimed to determine the impact of preoperative exposure to intravenous contrast for CT and the risk of developing postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery.This prospective, multicentre cohort study included adults undergoing gastrointestinal resection, stoma reversal or liver resection. Both elective and emergency procedures were included. Preoperative exposure to intravenous contrast was defined as exposure to contrast administered for the purposes of CT up to 7 days before surgery. The primary endpoint was the rate of AKI within 7 days. Propensity score-matched models were adjusted for patient, disease and operative variables. In a sensitivity analysis, a propensity score-matched model explored the association between preoperative exposure to contrast and AKI in the first 48 h after surgery.A total of 5378 patients were included across 173 centres. Overall, 1249 patients (23·2 per cent) received intravenous contrast. The overall rate of AKI within 7 days of surgery was 13·4 per cent (718 of 5378). In the propensity score-matched model, preoperative exposure to contrast was not associated with AKI within 7 days (odds ratio (OR) 0·95, 95 per cent c.i. 0·73 to 1·21; P = 0·669). The sensitivity analysis showed no association between preoperative contrast administration and AKI within 48 h after operation (OR 1·09, 0·84 to 1·41; P = 0·498).There was no association between preoperative intravenous contrast administered for CT up to 7 days before surgery and postoperative AKI. Risk of contrast-induced nephropathy should not be used as a reason to avoid contrast-enhanced CT.El objetivo de este estudio fue determinar el impacto de la exposición preoperatoria al contraste intravenoso para la tomografía computarizada (TC) y el riesgo de desarrollar insuficiencia renal aguda (IRA) postoperatoria en pacientes sometidos a cirugía gastrointestinal mayor. MÉTODOS: Este estudio de cohorte prospectivo y multicéntrico incluyó adultos sometidos a una resección gastrointestinal, cierre de estoma o resección hepática. Se incluyeron tanto procedimientos electivos como urgentes. La exposición al contraste intravenoso preoperatorio se definió como la administración de contraste para la realización de una TC durante los 7 días previos a la cirugía. El criterio de valoración principal fue la tasa de IRA a los 7 días. Se utilizaron modelos de puntuación de propensión emparejados (propensity score matched, PSM) ajustados por paciente, enfermedad y variables operatorias. Los resultados del modelo se presentan como razón de oportunidades (odds ratio, OR) e i.c. del 95%. En un análisis de sensibilidad, se examinó la asociación entre la exposición preoperatoria al contraste y la IRA en las primeras 48 horas después de la cirugía mediante un modelo de PSM.Se incluyeron un total de 5.378 pacientes de 173 centros. Globalmente, el 23,2% (n = 1.249) de los pacientes recibieron medios de contraste intravenosos. La tasa global de IRA postoperatoria a los 7 días fue del 13,4% (718/5.378). En el modelo de puntuación de propensión emparejado, la exposición preoperatoria al contraste no se asoció con IRA a los 7 días (OR 0,95; i.c. del 95%: 0,73-1,21; P = 0,669). En el análisis de sensibilidad no se observó una asociación entre la administración de contraste preoperatorio y la IRA postoperatoria a las 48 horas (OR 1,09; i.c. del 95% 0,84-1,41; P = 0,498). CONCLUSIÓN: No hubo asociación entre la administración preoperatoria de contraste intravenoso para tomografías computarizadas durante los 7 días previos a la cirugía y la IRA postoperatoria. El riesgo de nefropatía inducida por el contraste no debe usarse de manera rutinaria como una razón para evitar la práctica de un TC con contraste.

Published
2019

21. Association between peri-operative angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers and acute kidney injury in major elective non-cardiac surgery: a multicentre, prospective cohort study

Author

Alvin Thomas, Rahul Bhome, Teo Lopez Bernal, Prashant Patel, Owen Thorpe, Conor Keogh, Raiyyan Aftab, Muhamed Farhan-Alanie, DEVENDER MITTAPALLI, Matthew Chan, Aditya Borakati, Roshni Bhudia, Christopher Graham, Vinci Naruka, Moritz Schramm, Michael Kerin, Nicholas Wroe, Samian Sulaiman, Michael Stoddart, James Fitzgerald, Matthew Hague, Shaikh Sanjid Seraj, Katie Dunleavy, Emily Greenan, Samira Bell, Robert Whitham, Hannah Charlotte Copley, Clementina Calabria, Daniel Ahern, Abdul-Rahman Gomaa, Joseph Yates, Fraser Peck, Chetan Khatri, Janet Martin, Martin Connor, Thomas Robert William Ward, Shyam Gokani, Thomas Pinkney, Luke McMenamin, Liam Cato, Sameera A, Edward Balai, Timothy Shao Ern Tan, Sogha Khawari, Siew Yim Loh, Jonathan Lund, Peter Coe, Stephen Robinson, Ledibabari Ngaage, STARSurg Collaborative, Joshua Burke, Melika Akhbari, P. Ronan O'Connell, James Glasbey, Roshan Joseph, Thomas Gardner, Jonathan Bannard-Smith, Catrin Morgan, Ewen Harrison, Paul Glen, Laurie Rigueros Springford, Chia Yew Kong, Claire Donohoe, Heather Davis, Richard Bogle, Tom Abbott, Elizabeth Wootton, Justine Davies, Mehnoor Khaliq, Viren Ahluwalia, Sam Myers, Alex Elizabeth Ward, Sivesh K Kamarajah, Joanna Osmanska, Raoul Charles Coombes, Oliver Warren, John Prowle, Harry VM Spiers, Kenneth A McLean, Thomas Ashdown, Katherine Bull, Paul Ridgway, Fortis Gaba, Hew David Torrance, Dalvir Bajwa, Emanuele Gammeri, Rebecca Spencer, Adam Gwozdz, Kirtan Patel, Jaspreet Kaur Seehra, Chung Shen Chean, and Fahad Mahmood

Subjects
Male, medicine.medical_specialty, Population, Angiotensin-Converting Enzyme Inhibitors, Comorbidity, Drug Administration Schedule, Perioperative Care, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Postoperative Complications, 030202 anesthesiology, Risk Factors, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, education, Prospective cohort study, Digestive System Surgical Procedures, Aged, Aged, 80 and over, education.field_of_study, Withholding Treatment, biology, business.industry, Acute kidney injury, Angiotensin-converting enzyme, Perioperative, Acute Kidney Injury, Middle Aged, medicine.disease, United Kingdom, Anesthesiology and Pain Medicine, Elective Surgical Procedures, Propensity score matching, biology.protein, Female, business, Ireland
Abstract

The peri‐operative use of angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers is thought to be associated with an increased risk of postoperative acute kidney injury. To reduce this risk, these agents are commonly withheld during the peri‐operative period. This study aimed to investigate if withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers peri‐operatively reduces the risk of acute kidney injury following major non‐cardiac surgery. Patients undergoing elective major surgery on the gastrointestinal tract and/or the liver were eligible for inclusion in this prospective study. The primary outcome was the development of acute kidney injury within seven days of operation. Adjusted multi‐level models were used to account for centre‐level effects and propensity score matching was used to reduce the effects of selection bias between treatment groups. A total of 949 patients were included from 160 centres across the UK and Republic of Ireland. From this population, 573 (60.4%) patients had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers withheld during the peri‐operative period. One hundred and seventy‐five (18.4%) patients developed acute kidney injury; there was no difference in the incidence of acute kidney injury between patients who had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers continued or withheld (107 (18.7%) vs. 68 (18.1%), respectively; p = 0.914). Following propensity matching, withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers did not demonstrate a protective effect against the development of postoperative acute kidney injury (OR (95%CI) 0.89 (0.58–1.34); p = 0.567).

Published
2018
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22. Corrigendum to 'Quality metrics for the evaluation of Rapid Response Systems: Proceedings from the third international consensus conference on Rapid Response Systems' [Resuscitation 141 (2019) 1–12]

Author

Isabel Gonzalez, Helen Haskell, Daryl A Jones, Helen Hogan, Francesca Rubulotta, Michael A. DeVita, Jonathan Bannard-Smith, Lesley Durham, Rashan Haniffa, Christian P Subbe, Ratapum Champunot, Christopher Hancock, Dana P. Edelson, Alison V Phillips, Ralph K. L. So, James Malycha, Cor J. Kalkman, Geoffrey K. Lighthall, Jacinda L. Bunch, Melody Ni, John Welch, and Jillian Hartin

Subjects
Resuscitation, business.industry, media_common.quotation_subject, Published Erratum, Consensus conference, MEDLINE, Emergency Nursing, medicine.disease, Emergency Medicine, Medicine, Quality (business), Medical emergency, Cardiology and Cardiovascular Medicine, business, Rapid response, media_common
Published
2019
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23. Preoperative assessment of the patient with kidney disease

Author

Simon Forrington and Jonathan Bannard-Smith

Subjects
Nephrology, medicine.medical_specialty, Kidney, business.industry, Acute kidney injury, Disease, Perioperative, Critical Care and Intensive Care Medicine, medicine.disease, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Internal medicine, Intensive care, medicine, Risk factor, Intensive care medicine, business, Kidney disease
Abstract

The kidneys play a central role in the homeostasis of fluid, electrolyte and acid–base balance, whilst ensuring the efficient excretion of water-soluble waste products. They also have ancillary functions such as the production of erythropoietin, their crucial contribution to vitamin D metabolism and their neuro-hormonal influence over blood pressure. When kidneys fail a host of pathophysiological changes ensue resulting in both acute and chronic disease, which carry significant risk to patients and burden on healthcare resources. Acute kidney injury (AKI), chronic kidney disease (CKD) and acute-on-chronic kidney failure are increasingly common clinical entities, presenting significant challenges to the perioperative physician. The presence of renal disease is an independent risk factor for increased morbidity, mortality and length of hospital and intensive care stay. This article focuses on the clinical anaesthetic assessment of the renal patient prior to surgery.

Published
2015
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25. Defining the characteristics and expectations of fluid bolus therapy: a worldwide perspective

Author

Michael Joannidis, Glenn Hernandez, Jason Phua, Du Bin, Martin Matejovic, Anders Perner, Guy A. Richards, Neil J Glassford, Jacques Duranteau, Heleen Oudemans van Straaten, Erica Wilkman, Antoine G. Schneider, Glenn M Eastwood, Isabella Tsuji, Kianoush Kashani, Ville Pettilä, Rinaldo Bellomo, Shigehiko Uchino, Michael Bailey, Eric Hoste, Aiko Tanaka, Arnaldo Dubin, Sarah Louise Jones, Atul P Kulkarni, John A. Kellum, Konrad Reinhart, Johan Mårtensson, Jonathan Bannard-Smith, Christina Lluch Candal, Sean M. Bagshaw, Yaseen M. Arabi, Alex Puxty, Alistair Nichol, Giovanni Landoni, Jorge Enrique Echeverri, Nor'azim Modh Yunos, HUS Perioperative, Intensive Care and Pain Medicine, Anestesiologian yksikkö, Department of Diagnostics and Therapeutics, Clinicum, Glassford, Nj, Mårtensson, J, Eastwood, Gm, Jones, Sl, Tanaka, A, Wilkman, E, Bailey, M, Bellomo, R, GLobal OBservational Evaluations in the ICU (GLOBE-ICU), Investigator, Arabi, Y, Bagshaw, Sm, Bannard-Smith, J, Bin, D, Dubin, A, Duranteau, J, Echeverri, J, Hoste, E, Joannidis, M, Kashani, K, Kellum, J, Kulkarni, Ap, Landoni, G, Candal, Cl, Matejovic, M, Yunos, Nm, Nichol, A, van Straaten, Ho, Perner, A, Pettila, V, Phua, J, Hernandez, G, Puxty, A, Reinhart, K, Richards, G, Schneider, A, Tsuji, I, and Uchino, S

Subjects
medicine.medical_treatment, Critical Care and Intensive Care Medicine, Global Health, 0302 clinical medicine, Surveys and Questionnaires, Surveys and Questionnaire, 030212 general & internal medicine, Practice Patterns, Physicians', Fluid bolus, Saline, Fluid resuscitation, INTENSIVE-CARE UNITS, 3. Good health, REPLACEMENT, Intensive Care Units, Anesthesia, Critical Illne, CRITICALLY-ILL ADULTS, Human, medicine.medical_specialty, Mean arterial pressure, GOAL-DIRECTED RESUSCITATION, Critical Care, Beats per minute, Critical Illness, Intensive Care Unit, HYDROXYETHYL STARCH 130/0.4, HUMAN ALBUMIN, 03 medical and health sciences, Fluid bolus therapy, Intensive care, Heart rate, medicine, Humans, Intensive care medicine, METAANALYSIS, Isotonic Solution, Urinary output, Internet, Septic shock, business.industry, MORTALITY, SEPTIC SHOCK, 030208 emergency & critical care medicine, Crystalloid Solutions, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, SEVERE SEPSIS, Critical care, 3121 General medicine, internal medicine and other clinical medicine, Ciencias Médicas, Fluid Therapy, Isotonic Solutions, Hemodynamic optimization, business
Abstract

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes., Facultad de Ciencias Médicas

Published
2016

26. Clinical outcomes of patients seen by Rapid Response Teams: A template for benchmarking international teams

Author

Lesley Durham, Daryl A Jones, Rinaldo Bellomo, Jonathan Bannard-Smith, Christian P Subbe, John Welch, and Geoffrey K. Lighthall

Subjects
Research design, Male, medicine.medical_specialty, Critical Care, Denmark, International Cooperation, Vital signs, Emergency Nursing, urologic and male genital diseases, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Health care, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Intensive care medicine, Rapid response team, Prospective cohort study, Aged, Netherlands, business.industry, Australia, 030208 emergency & critical care medicine, Middle Aged, Early warning score, Intensive care unit, Survival Analysis, United Kingdom, United States, Benchmarking, Clinical research, Outcome and Process Assessment, Health Care, Research Design, Emergency medicine, Emergency Medicine, Female, Cardiology and Cardiovascular Medicine, business, Hospital Rapid Response Team
Abstract

The study was developed to characterize short-term outcomes of deteriorating ward patients triggering a Rapid Response Team (RRT), and describe variability between hospitals or groups thereof.We performed an international prospective study of Rapid Response Team (RRT) activity over a 7-day period in February 2014. Investigators at 51 acute hospitals across Australia, Denmark, the Netherlands, USA and United Kingdom collected data on all patients triggering RRT review concerning the nature, trigger and immediate outcome of RRT review. Further follow-up at 24h following RRT review focused on patient orientated outcomes including need for admission to critical care, change in limitations of therapy and all cause mortality.We studied 1188 RRT activations. Derangement of vital signs as measured by the National Early Warning Score (NEWS) was more common in non-UK hospitals (p=0.03). Twenty four hour mortality after RRT review was 10.1% (120/1188). Urgent transfer to ICU or the operating theatre occurred in 24% (284/1188) and 3% (40/1188) of events, respectively. Patients in the UK were less likely to be admitted to ICU (31% vs. 22%; p=0.017) and their median (IQR) time to ICU admission was longer [4.4 (2.0-11.8) vs. 1.5 (0.8-4.4)h; p0.001]. RRT involvement lead to new limitations in care in 28% of the patients not transferring to the ICU; in the UK such limitations were instituted in 21% of patients while this occurred in 40% of non-UK patients (p0.001).Among patients triggering RRT review, 1 in 10 died within 24h; 1 in 4 required ICU admission, and 1 in 4 had new limitations in therapy implemented. We provide a template for an international comparison of outcomes at RRT level.

Published
2016

28. The Barriers and Enablers to Single-Specialty Status in Critical Care

Author

Maurice Le Guen, Jonathan Bannard-Smith, and Timothy Fudge

Subjects
03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, 030228 respiratory system, business.industry, Family medicine, Specialty, medicine, 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, business
Published
2016
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29. Twelve tips for junior doctors interested in a career in medical education

Author

Sophie Bishop, Suzanne Gawne, Jonathan Bannard-Smith, and Neel Halder

Subjects
Medical education, Medical staff, Career Choice, Education, Medical, business.industry, MEDLINE, Developing country, General Medicine, Nature versus nurture, Education, Career Mobility, Medical Staff, Hospital, Medicine, Humans, business, Career choice
Abstract

Background: As with the many specialities within medicine, the expanding field of medical education is becoming a more formal and professionalised arena.Aim: This article aims to assist junior doctors wishing to pursue formal educational roles in their future careers.Methods:We offer twelve tips for junior doctors with these aspirations in mind, exploring a range of potential roles, resources and opportunities available.Results: Twelve practical suggestions on how junior doctors can nurture their portfolios of evidence and subsequent future careers in medical education.Conclusions: The developing world of medical education is becoming evermore structured and professionalised. Educators of the future will need to demonstrate evidence of their knowledge, skills and experience in the field in order to effectively assume and perform educational roles.

Published
2012

30. Use of an electronic early warning score and mortality for patients admitted out of hours to a large teaching hospital

Author

S Abbas, Jane Eddleston, C Fullwood, Jonathan Bannard-Smith, Sarah Ingleby, and S Jones

Subjects
Excess mortality, medicine.medical_specialty, Medical staff, business.product_category, business.industry, Track and trigger, Critical Care and Intensive Care Medicine, Early warning score, Teaching hospital, Out of hours, Poster Presentation, Emergency medicine, medicine, University teaching, Pager, business
Abstract

There is widespread concern regarding excess mortality for patients admitted to hospital out of hours. We introduced an electronic track and trigger system (Patientrack) with automated alerts in a large university teaching hospital between 2010 and 2012. The system computes the patient's early warning score and alerts medical staff via a pager. It is operational 24 hours a day, 7 days a week and could be an effective tool to reduce variations in mortality throughout the working week.

Published
2015
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31. Early versus late renal replacement therapy in acute kidney injury: the search for a definition of timing continues

Author

Stephen Mousdale and Jonathan Bannard-Smith

Subjects
medicine.medical_specialty, Critically ill, business.industry, medicine.medical_treatment, Acute kidney injury, urologic and male genital diseases, Critical Care and Intensive Care Medicine, medicine.disease, Intensive care unit, female genital diseases and pregnancy complications, law.invention, law, Health evaluation, medicine, Rifle, Renal replacement therapy, Stage (cooking), Intensive care medicine, business, Late initiation
Abstract

We read with interest the systematic review by Karvellas and colleagues on early versus late renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) [1]. The authors rightly cite enormous heterogeneity between the 15 studies reviewed as a key concern. We would like to focus on the varied approach and lack of consensus in defining early and late initiation of RRT, as all of the 15 studies quote different definitions in their methods. Even those utilising similar markers and criteria for AKI - for example, the RIFLE criteria [2] (two studies) or blood urea and nitrogen (four studies) - utilised and interpreted them in very different ways when distinguishing early and late initiation of RRT. None of the studies reviewed used the Acute Kidney Injury Network (AKIN) criteria [3]. Having applied the AKIN criteria to data from our 20-bed critical care unit for all patients receiving RRT in 2009 (n = 158), we also failed to show RRT initiated at an early stage of AKI to be of benefit in terms of critical care or hospital survival. Figure ​Figure11 shows a higher rate of hospital mortality in patients with AKIN stage 1 AKI (P = 0.01). Patient characteristics including age, sex and Acute Physiology and Chronic Health Evaluation scores were similar across all groups. In view of our experience and Karvellas and colleagues' conclusions, surely the matter of greatest urgency prior to any multicentre trial is establishing a satisfactory definition for early and late initiation of RRT. Figure 1 Hospital survival based on acute kidney injury staging. Histogram for hospital survival based on acute kidney injury (AKI) staging according to Acute Kidney Injury Network criteria [3] (n = 143). RRT, renal replacement therapy.

Published
2011
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32. Haemodynamic and biochemical responses to fluid bolus therapy with human albumin solution, 4% versus 20%, in critically ill adults

Author

Jonathan Bannard-Smith, Paschal Alexander, Neil Glassford, Chan, Matthew J., Matthew Lee, Wong, Benjamin T., Grant Crawford, michael bailey, and Rinaldo Bellomo

Subjects
Adult, Male, Critical Care, Critical Illness, Liver Diseases, Blood Pressure, Middle Aged, Sodium Chloride, Renal Replacement Therapy, Creatinine, Fluid Therapy, Humans, Female, Serum Albumin, Aged, Retrospective Studies
Abstract

Fluid bolus therapy (FBT) is common in critically ill patients. With the exception of use in patients with traumatic brain injury, FBT with human albumin solution (HAS) appears safe and perhaps superior in severe sepsis.To determine the physiological effects of FBT with 4% v 20% HAS.A retrospective observational study of 202 critically ill patients receiving FBT with HAS in a tertiary intensive care unit between April 2012 and March 2013.FBT was instituted with 4% or 20% HAS, according to clinician preference.We compared biochemical and haemodynamic data between groups at baseline and at 1, 2 and 4 hours after FBT.Patients who had received 20% HAS had more liver disease, a greater need for renal replacement therapy and higher Acute Physiology and Chronic Health Evaluation III scores on admission. Patients who had received 4% HAS received a median volume of 500 mL (interquartile range [IQR], 350-500 mL), compared with 100mL (IQR, 100- 200 mL) in the 20% HAS group (P0.0001); a median of 70 mmol v 10 mmol of sodium (P0.0001); and a median of 64 mmol v 2 mmol of chloride (P0.0001). There was a trend toward higher mean arterial pressures in the 20% group after FBT (78.2 mmHg v 76.4 mmHg, P = 0.03). There were no significant differences in the absolute or percentage change for any haemodynamic parameters. Serum biochemical test results were comparable with a non-significant signal of higher serum chloride and more negative base excess in patients receiving 4% HAS.Haemodynamically, FBT with 100mL of 20% HAS performs in an equivalent way to 500 mL of 4% HAS but delivers much less fluid, sodium and chloride.

34. Small volume resuscitation with 20% albumin in intensive care: physiological effects : The SWIPE randomised clinical trial

Author

Maria Cronhjort, Aiko Tanaka, Neil J Glassford, Johan Mårtensson, Nora Luethi, Jonathan Bannard-Smith, Andrew D. Bersten, Shivesh Prakash, Glenn M Eastwood, Shailesh Bihari, Rinaldo Bellomo, Michael Bailey, Nicolas Rey de Castro, Marco Crisman, Patryck Lloyd-Donald, Marcus Ottochian, Luca Cioccari, and Agnes Huang

Subjects
Adult, Male, Resuscitation, Critical Care, medicine.medical_treatment, 610 Medicine & health, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Intensive care, Albumins, Medicine, Humans, Renal replacement therapy, Aged, Mechanical ventilation, business.industry, Albumin, Australia, 030208 emergency & critical care medicine, Middle Aged, Water-Electrolyte Balance, Intensive care unit, United Kingdom, Anesthesia, Fluid Therapy, Female, business
Abstract

PURPOSE We set out to assess the resuscitation fluid requirements and physiological and clinical responses of intensive care unit (ICU) patients resuscitated with 20% albumin versus 4-5% albumin. METHODS We performed a randomised controlled trial in 321 adult patients requiring fluid resuscitation within 48 h of admission to three ICUs in Australia and the UK. RESULTS The cumulative volume of resuscitation fluid at 48 h (primary outcome) was lower in the 20% albumin group than in the 4-5% albumin group [median difference - 600 ml, 95% confidence interval (CI) - 800 to - 400; P

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35. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19

Author

Angus, Derek, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa, Horvat, Christopher, Hullegie, Sebastiaan, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, Mcauley, Daniel, Mcglothin, Anna, Mcguinness, Shay, Mcverry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger, Mcarthur, Colin, Webb, Steven, Gordon, Anthony, NIHR, Hôpital Raymond Poincaré [AP-HP], Writing Committee for the REMAP-CAP Investigators, Farah Al-Beidh, Derek Angus, Djillali Annane, Yaseen Arabi, Wilma van Bentum-Puijk, Scott Berry, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Meredith Buxton, Allen Cheng, Menno De Jong, Lennie Derde, Lise Estcourt, Herman Goossens, Anthony Gordon, Cameron Green, Rashan Haniffa, Francois Lamontagne, Patrick Lawler, Edward Litton, John Marshall, Colin McArthur, Daniel McAuley, Shay McGuinness, Bryan McVerry, Stephanie Montgomery, Paul Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Kathryn Rowan, Christopher Seymour, Anne Turner, Frank van de Veerdonk, Steve Webb, Ryan Zarychanski, Lewis Campbell, Andrew Forbes, David Gattas, Stephane Heritier, Lisa Higgins, Peter Kruger, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Paul Young, Sean Bagshaw, Nick Daneman, Niall Ferguson, Cheryl Misak, Marlene Santos, Sebastiaan Hullegie, Mathias Pletz, Gernot Rohde, Kathy Rowan, Brian Alexander, Kim Basile, Timothy Girard, Christopher Horvat, David Huang, Kelsey Linstrum, Jennifer Vates, Richard Beasley, Robert Fowler, Steve McGloughlin, Susan Morpeth, David Paterson, Bala Venkatesh, Tim Uyeki, Kenneth Baillie, Eamon Duffy, Rob Fowler, Thomas Hills, Katrina Orr, Asad Patanwala, Steve Tong, Mihai Netea, Shilesh Bihari, Marc Carrier, Dean Fergusson, Ewan Goligher, Ghady Haidar, Beverley Hunt, Anand Kumar, Mike Laffan, Patrick Lawless, Sylvain Lother, Peter McCallum, Saskia Middeldopr, Zoe McQuilten, Matthew Neal, John Pasi, Roger Schutgens, Simon Stanworth, Alexis Turgeon, Alexandra Weissman, Neill Adhikari, Matthew Anstey, Emily Brant, Angelique de Man, Francois Lamonagne, Marie-Helene Masse, Andrew Udy, Donald Arnold, Phillipe Begin, Richard Charlewood, Michael Chasse, Mark Coyne, Jamie Cooper, James Daly, Iain Gosbell, Heli Harvala-Simmonds, Tom Hills, Sheila MacLennan, David Menon, John McDyer, Nicole Pridee, David Roberts, Manu Shankar-Hari, Helen Thomas, Alan Tinmouth, Darrell Triulzi, Tim Walsh, Erica Wood, Carolyn Calfee, Cecilia O’Kane, Murali Shyamsundar, Pratik Sinha, Taylor Thompson, Ian Young, Shailesh Bihari, Carol Hodgson, John Laffey, Danny McAuley, Neil Orford, Ary Neto, Michelle Detry, Mark Fitzgerald, Roger Lewis, Anna McGlothlin, Ashish Sanil, Christina Saunders, Lindsay Berry, Elizabeth Lorenzi, Eliza Miller, Vanessa Singh, Claire Zammit, Wilma van Bentum Puijk, Wietske Bouwman, Yara Mangindaan, Lorraine Parker, Svenja Peters, Ilse Rietveld, Kik Raymakers, Radhika Ganpat, Nicole Brillinger, Rene Markgraf, Kate Ainscough, Kathy Brickell, Aisha Anjum, Janis-Best Lane, Alvin Richards-Belle, Michelle Saull, Daisy Wiley, Julian Bion, Jason Connor, Simon Gates, Victoria Manax, Tom van der Poll, John Reynolds, Marloes van Beurden, Evelien Effelaar, Joost Schotsman, Craig Boyd, Cain Harland, Audrey Shearer, Jess Wren, Giles Clermont, William Garrard, Kyle Kalchthaler, Andrew King, Daniel Ricketts, Salim Malakoutis, Oscar 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Ferguson, Katharine Sellers, Joanne Bradley-Potts, David Yates, Isobel Birkinshaw, Kay Kell, Nicola Marshall, Lisa Carr-Knott, Charlotte Summers, and Mégarbane, Bruno

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, General Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Writing Committee for the REMAP-CAP Investigators, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, General & Internal Medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 11 Medical and Health Sciences
Abstract

Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Published
2020
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