Reply to Editorial
Angelique de Man
Bodil Steen Rasmussen
There have been several high quality trials comparing different oxygen targets ic critically ill mechanically ventilated patients over the past few years. The results have largely shown similar outcomes between higher and lower target oxygen levels, but this hasn't been conclusive. The LOCO2 trial reported harm from a lower oxygen target, culminating in the trial been terminated early.
The PILOT trial compares three different oxygen targets; 90% vs 94% vs 98%, in 2500 critically ill mechanically ventilated patients. It has been run by the highly productive Pragmatic Critical Care Research Group in the USA.
The trial result will be presented by the chief investigator, Matthew Semler, from Nashville, USA. The editorial will be delivered by Paul Young from Wellington, New Zealand (also chief investigator for ICU-ROX and MEGA-ROX trials). The discussion panel includes the chief investigators for the HOT-ICU trial (Bodil Steen Rasmussen; Aalborg, Denmark), LOCO2 (Gilles Capellier, Besançon, France) and O2-ICU (Angelique de Man, Amsterdam, The Netherlands). Victoria Cornelius (London, England) joins us as our expert statistician and methodologist.
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Clinical Professor, Anaesthesia and Intensive Care Medicine, Aalborg University Hospital and President of EACTA
Matthew W. Semler MD, MSc is an Assistant Professor of Medicine and Biomedical Informatics in the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University. Dr. Semler is a critical care physician and Associate Director of the Medical Intensive Care Unit at Vanderbilt University. Dr. Semler’s federally-funded research identifies non-patient-centered variation in current clinical practice, embeds pragmatic randomized trials into clinical care to understand which treatments produce the best outcomes for which patients, and implements the results into practice. Randomized trials he has helped lead, including six published in the New England Journal of Medicine or JAMA, have challenged longstanding dogma around common practices in fluid management, airway management, and respiratory support. Dr. Semler serves as Chair of the Steering Committee for the Pragmatic Critical Care Research Group, co-director of the Inpatient Division of the Learning Healthcare System at Vanderbilt University, and a member of the protocol committee for trials within the NHLBI PETAL Network.
Prof Young is Deputy Director and Intensive Care Programme Director at the Medical Research Institute of New Zealand, Co-Clinical Lead of the Intensive Care Unit at Wellington Hospital, and the Medical Director of Wakefield Hospital in Wellington, New Zealand. He has >$40 million in competitive research funding in the past 5 years, including 22 grants from the Health Research Council of New Zealand, and multiple additional grants from Australian, European, and Canadian funders. His awards include a Health Research Council of New Zealand Clinical Practitioners Fellowship (2017-2022).
In 2020, Prof Young was an author of two of the top 10 most-viewed non-COVID related JAMA papers (VITAMINS & PEPTIC). These two papers were viewed more than 220,000 times in 2020. The ICU-ROX trial was selected by the editors of the NEJM as one of the top 14 most notable NEJM studies of 2020. Prof Young was presented with the Medicines New Zealand Value of Medicines award for his NEJM-published research on paracetamol therapy in the critically ill, and the Liley Medal recognising the most important health research publication from a New Zealand investigator for the calendar year awarded to Prof Young for the SPLIT trial, published in JAMA in 2015, evaluating intravenous fluid therapy in critically ill patients.
Professor of Anaesthesia and Intensive Care Medicine at Aalborg University Hospital and Aalborg University, Aalborg, Denmark
Bodil Steen Rasmussen, MD, PhD is Professor of Anaesthesia and Intensive Care Medicine at Aalborg University Hospital and Aalborg University, Aalborg, Denmark. Her research programme focuses on critically ill adults acutely admitted to the intensive care unit and specifically patients with acute hypoxaemic respiratory failure. Primary investigator of a large randomised clinical trial evaluating two oxygenation targets in patients with acute hypoxaemic respiratory failure, amended to include patients with severe SARS-CoV-2 pneumonia with long-term follow-up focusing on pulmonary dysfunction and cognitive impairment. Additionally, mechanistic studies looking at metabonomic changes in blood and exhaled breath condensate following oxygen exposure.
Professor of Intensive Care Medicine at Université de Franche-Comté, Besançon, France
Prof Gilles Capellier is Professor of Intensive Care Medicine at Université de Franche-Comté, Besançon, France. His qualifications include an MD; certification as a Critical Care Physician from the Hôpital Claude Bernard, Paris; a Master of Science degree in Respiratory and Circulatory Physiology and Pathophysiology (Thesis title: Pulmonary neutrophils accumulation during peritonitis induced by cecal ligation and perforation); and a PhD (Thesis title: Pulmonary oxygen toxicity - demonstration of clinical and experimental tolerance). Gilles' main research foci are Acute Respiratory Distress Syndrome (ARDS), oxygen toxicity tolerance, and ICU management of ARDS including extracorporeal membrane oxygenation (ECMO). He is also interested in ICU organisation and quality-safety in care. His experience includes a year as a Clinical Fellow and a Clinical Research Fellow at the Toronto General Hospital, Canada.
Dr Angelique de Man is an intensivist at Amsterdam UMC in the Netherlands. She led the O2-ICU trial, comparing target oxygen ranges of 8 to 12 kPa and 14 to 18 kPa, in 400 ICU patients. This was published in JAMA in August 2021. She has extensive experience in clinical and, since she is also a medical biologist, in translational
Her domains of expertise in research comprise hyperoxia, cardiac arrest, vitamin C and micronutrients in critical care. She completed 3 RCT’s on folic acid supplementation in diabetes, oxygen targets in the ICU and hyperoxia in cardiac surgery. A fourth one on vitamin C in post cardiac arrest syndrome is almost completed.
Furthermore, she was the last author in 3 meta-analyses; addressing the vasoconstrictive effect of hyperoxia in preclinical and clinical studies. She was coauthor of the ESPEN micronutrient guidelines and is currently leader of the micronutrients working group of the ESICM.
Professor of Medical Statistics and Trials Methodology, Imperial College London.
Victoria Cornelius is Professor in Medical Statistics and Trials Methodology at Imperial College London, as well as Director of Imperial Clinical Trials Unit. She leads the Child Health trial portfolio and is an Academic Lead for the Research Design Service (RDS) London.
Victoria's trials research has included evaluating drug interventions across clinical areas including asthma & allergy, dermatology, and cancer, and complex interventions in mental health and surgery. Her statistical research is in the use of time-to-event signal detection methods to identify adverse drug reactions, and the selection and presentation of harm information in randomised controlled trials. Victoria is passionate about translating best statistical practice into applied research. She has collaborated and led national research projects in laboratory studies, feasibility trials, and early phase clinical trials research to support methods translation. She established the NIHR Statistics Group in 2011 with the support of NOCRI which she subsequently co-led until March 2017. Victoria is a member of the NIHR Academy Doctoral fellowship board and Joint Global Health Trials funding Committee.