Research In Intensive Care Medicine Research Articles

Contribution of open access databases to intensive care medicine research: a scoping review (Preprint)

Contribution of open access databases to intensive care medicine research: a scoping review (Preprint)

Informed Consent in Time-critical Emergency and Intensive Care Medicine Research in Patients Who Lack Capacity: New Zealand Journey and the Global Context

Informed Consent in Time-critical Emergency and Intensive Care Medicine Research in Patients Who Lack Capacity: New Zealand Journey and the Global Context

Curiosity, Opportunity, and Luck: Were the 1970s Different?

Control of Breathing Using an Extracorporeal Membrane Lung. By T Kolobow, L Gattinoni, TA Tomlinson, JE Pierce. Anesthesiology 1977; 46:138-41. Reprinted with permission. Body Position Changes Redistribute Lung Computed-Tomographic Density in Patients with Acute Respiratory Failure. By L Gattinoni, P Pelosi, G Vitale, A Pesenti, L D'Andrea, D Mascheroni. Anesthesiology 1991; 74:15-23. Reprinted with permission. Dr. Gattinoni's scientific career was primarily driven by curiosity. His generation was not formally trained, but he was part of a community of young and enthusiastic colleagues who were forging a new discipline: intensive care medicine. The most significant opportunity of Dr. Gattinoni's career was becoming the research fellow of a visionary genius, Dr. Theodor Kolobow, who focused on extracorporeal carbon dioxide removal after the failure of the first trial on extracorporeal membrane oxygenation. CO2 removal, by allowing control over the intensity of mechanical ventilation, opened the path to "lung rest" to prevent ventilator-induced lung injury. A unique opportunity for research was the spontaneous birth of a network of scientists who became friends in the European Group of Research in Intensive Care Medicine. In this environment, it was possible to develop core concepts such as the "baby lung" and to understand the mechanisms underlying computed tomography-density redistribution in the prone position. Physiology guided us in the 1970s, and understanding mechanisms remains of paramount importance today.

Cuban Scientific Production on Intensive Care and Emergency Medicine in Scopus (2019-2021)

Introduction: health research is a key link in scientific development. Research in intensive care medicine is essential to improve medical care, generate new treatments, reduce mortality and save resources. Aim: to characterize Cuban scientific production in Intensive Care and Emergency Medicine in Scopus between 2019 and 2021. Method: an observational, descriptive, bibliometric study of articles with Cuban authorship published in Scopus between 2019 and 2021 that responded to the areas Emergency Medicine and Critical Care and Intensive Care Medicine was carried out. SciVal was used to obtain and analyze the data. Results: 18 articles were published and 184 citations were received, with an average of 2.33 and 3.67 articles per year for the areas Emergency Medicine and Critical Care and Intensive Care Medicine respectively; the percentage of excellence was 60 and 37.5 % respectively. For both areas, international collaboration predominated. The most productive author was DrC. Frank Daniel Martos-Benítez and the institution was the Hospital Clínico Quirúrgico "Hermanos Ameijeiras" (Ndoc=4, Authors=8, Ncit=33). Conclusions: there is a discreet increase in the annual scientific production when compared to previous periods, which was centered in first and second quartile journals. Collaboration, especially international collaboration, was shown to be standard in publication.

Reports from the 1st Young Investigator’s Day of the French Intensive Care Society

The Translational Research Committee of the French Intensive Care Society organized the first Young Investigator’s Day on October 18th 2019. This seminar gave young Intensive Care students the opportunity to present their Master’s or PhD research work to a college of expert researchers. For this first event, Professors Jean-Marc Cavaillon (Paris), Laurent Papazian (Marseille), Peter Radermacher (Ulm) et Hafid Ait-Oufella (Paris) kindly accepted to give young candidates their critical support. The subjects of presentations, covering the fields of neuroscience, immunology, hemodynamics and pharmacology illustrated the richness and diversity of translational research in Intensive Care Medicine.

Artificial intelligence in neurocritical care

Die Methoden der künstlichen Intelligenz (KI) halten Einzug in die Medizin. Die KI-assistierte Medizin ist die Zukunft, die es mitzugestalten gilt. Insbesondere supervidiertes, unsupervidiertes und bestärkendes Lernen werden als Methoden eine zentrale Rolle einnehmen. In der Intensivmedizin werden schwerkranke Patienten mit einem aufwendigen Monitoring versehen, um auf Veränderungen schnell zu reagieren. Diese Daten können genutzt werden, um Vorhersagemodelle zu trainieren und somit in der Lage zu sein, früher auf Veränderungen zu reagieren. Für das Training von Modellen werden große Datensätze benötigt. Eine Validierung der Modelle sollte an externen und unabhängigen Kohorten erfolgen. Prospektive Studien mit KI-Assistenz müssen zeigen, dass sie einen Vorteil für Patienten bringen. Wir stellen die wichtigsten Ressourcen anonymisierter Patientendaten zur Open-source-Nutzung für die KI-Forschung in der Intensivmedizin vor. Der Fokus liegt auf den neurologischen Krankheitsbildern auf der Intensivstation, daher geben wir eine Übersicht über bestehende Modelle zur Prädiktion von Outcome, Vasospasmen, intrakraniellem Druck und Bewusstsein. Um die Vorteile der KI in der Routine zu nutzen, werden weitere Modelle mit noch größeren Datensätzen benötigt. Internationale Kooperationen sind dafür zwingend notwendig. Die Validierung und ständige Überprüfung der Modelle wird eine Kernaufgabe der universitären Medizin sein, da diese Modelle sich während der Nutzung verändern können oder auch während des Trainings ein Bias entstehen kann. Ein konsequentes Engagement in der KI-Forschung ist nicht nur für die deutsche Universitätsmedizin, sondern auch für den Wirtschaftsstandort Deutschland wichtig.

Analysis of causality from observational studies and its application in clinical research in Intensive Care Medicine

Random allocation of treatment or intervention is the key feature of clinical trials and divides patients into treatment groups that are approximately balanced for baseline, and therefore comparable covariates except for the variable treatment of the study. However, in observational studies, where treatment allocation is not random, patients in the treatment and control groups often differ in covariates that are related to intervention variables. These imbalances in covariates can lead to biased estimates of the treatment effect. However, randomized clinical trials are sometimes not feasible for ethical, logistical, economic or other reasons. To resolve these situations, interest in the field of clinical research has grown in designing studies that are most similar to randomized experiments using observational (i.e. non-random) data. Observational studies using propensity score analysis methods have been increasing in the scientific papers of Intensive Care. Propensity score analyses attempt to control for confounding in non-experimental studies by adjusting for the likelihood that a given patient is exposed. However, studies with propensity indexes may be confusing, and intensivists are not familiar with this methodology and may not fully understand the importance of this technique. The objectives of this review are: to describe the fundamentals of propensity index methods; to present the techniques to adequately evaluate propensity index models; to discuss the advantages and disadvantages of these techniques.

How to improve quality of research in intensive care medicine.

This paper discusses several approaches to improve quality of research in intensive care medicine. The baseline standard of care is important in randomized controlled trials. If standard of care is low, trialists could consider improving this before starting the trial. Implementation studies and efficacy trials should not be mixed up. Trialists could further try to increase prognostic as well as predictive enrichment, e.g., through biological phenotyping. Robustness of statistical findings can increase by enrolling sufficiently high numbers of patients and minimizing loss to follow-up.

The intensive care medicine research agenda for airways, invasive and noninvasive mechanical ventilation.

In an important sense, support of the respiratory system has been a defining characteristic of intensive care since its inception. The pace of basic and clinical research in this field has escalated over the past twodecades, resulting in palpable improvement at the bedside as measured by both efficacy and outcome. As in all medical research, however, novel ideas built upon observations are continually proposed, tested, and either retained or discarded on the basis of the persuasiveness of the evidence. What follows are concise descriptions of the current standards of management practice in respiratory support, the areas of present-day uncertainty, and our suggested agenda for the near future of research aimed at testing current assumptions, probing uncertainties, and solidifying the foundation on which to base our progress to the next level.

A Qualitative Pilot Study on Donation After Cardiac Death (DCD)

Aim DCD is considered a viable solution to reduce organ shortage, but it raises serious ethical and psychological issues that cannot be ignored. Understanding what alters DCD acceptance by ICU caregivers is important to run a sustainable DCD program and to offer an adapted support for the personnel involved. The aim of our research was to shed new light on feelings experienced by caregivers when involved in DCD. Methods We conducted an exploratory qualitative study before the introduction of DCD to investigate how ICU caregivers at the Geneva University Hospitals perceive DCD and how they associate this practice to ethical interrogations. Our qualitative study was based on three semi-structured focus groups with a sample of twenty-four caregivers (nurses, physicians and care assistants). Results Our analysis of caregivers’ feelings toward DCD showed the presence of various stress factors which are perceived as potential barriers to DCD acceptance. The temporal proximity between therapeutic withdrawal decision and organ donation process introduces a sense of “conflict of duty” in caregivers. Brain death not being central in DCD, traditional landmarks in donation are lost, which makes caregivers uncomfortable with this procedure. Some ICU professionals are afraid of families’ and public’s judgment. Some of them may perceive incoherence between social desirability and individual values. Taking into account all these issues, we can also observe that the majority of caregivers are able to deal with these complexities; they do not reject DCD but on the contrary they made several suggestions which are intended to reduce psychological impact of DCD, such as a desire of objectivity regarding DCD criteria or the training of specialised professionals to achieve DCD process. They stated being in favour of organ donation and in addition, we also observe trust in the DCD program and a high level of support within ICU. Conclusion Our qualitative study highlights major psychological distress induced by DCD, which represents a potential barrier to DCD acceptance in ICU. However, we can also observe that caregivers are able to deal with DCD difficulties by proposing solutions which are intended to reduce its psychological impact. In view of our results, we can consider if the introduction of DCD in the ICU should be accompanied by a program of psychological support to help caregivers dealing with this new and demanding activity. A pilot study on the feelings experienced by the nursing and medical staff in the adult intensive care unit (ICU) of the Geneva University Hospitals. This study was financially supported by the Department of Anaesthesiology, Pharmacology and Intensive Care Medicine Research Fund. The Geneva University Hospital DCD program is financially supported by the Geneva University Hospitals Private Foundation. We also gratefully acknowledge the support of Dynèle Gautier and also all the adult intensive care unit who has always been highly collaborative.

A Quantitative Pilot Study on Donation after Cardiac Death (DCD)

Aim DCD is considered a viable solution to reduce organ shortage, but it raises serious ethical and psychological issues that cannot be ignored. Understanding what alters DCD acceptance by ICU caregivers is important to run a sustainable DCD program and to offer an adapted support for the personnel involved. The aim of our research was to shed new light on feelings experienced by caregivers regarding DCD. Methods We developed a questionnaire which aims to identify caregivers’ opinions concerning DCD. Our survey incorporates a list of questions to examine ethical issues regarding therapy withdrawal and organ donation. The sample includes ICU caregivers (physicians, nurses and care assistants) at the Geneva and Lausanne University Hospitals. Data were collected using LogiIC software and Survey Monkey and then analysed through Statistical Package for Social Sciences -SPSS V.22.0. In both hospitals, our research was conducted before the introduction of the DCD program. Results 106 ICU professionals responded, 66% nurses, 30% physicians and 4% care assistant. Analysis shows that the most crucial ethical issues concentrated around four main topics. 1) Presence of some doubts concerning the real reasons leading to withdrawal of life support: 42% of respondent think that withdrawal of life support decision was not always taken in the interest of the patient; 2) Satisfactory level of support within ICU during end-of-life care: 49% of ICU nurses feel being reasonably well supported and 47% feel rather well or very well supported; 3) Hastening of patient death because of palliative treatments isn’t a main source of concern: in Geneva respondents perceive that this acceleration rather gives them a sense of relieve (52%). Lausanne data also show that 80% of respondent claim that they do not feel any conflict of interest in this context; 4) Independence between the therapeutic withdrawal and the decision to donate is reasonably well preserved: 73% of caregivers do not feel any conflict of interest during DCD procedure. Finally, our survey demonstrate that ICU professional were in favour of organ donation not only in DBD context (97%) but also in DCD (94%). In addition, 70% of caregivers’ trust in DCD program development. Conclusions The introduction of DCD in the ICU, challenges the ethical values of caregivers. Nevertheless, our findings suggest that caregivers generally embrace DCD as a valid practice for patients who do not fulfil brain death criteria. A pilot study on DCD perceptions felt by the nursing and medical staff in adult intensive care unit (ICU) of Geneva University Hospitals and Lausanne University Hospital. This study was financially supported by the Department of Anaesthesiology, Pharmacology and Intensive Care Medicine Research Fund. The Geneva University Hospital DCD program is financially supported by the Geneva University Hospitals Private Foundation. We also gratefully acknowledge the support of Dr. Didier Tassaux, MD, PhD; Josette Simon and also all the ICU personnel who has always been highly collaborative.

The Intensive Care Medicine research agenda on critically ill oncology and hematology patients.

Over the coming years, accelerating progress against cancer will be associated with an increased number of patients who require life-sustaining therapies for infectious or toxic chemotherapy-related events. Major changes include increased number of cancer patients admitted to the ICU with full-code status or for time-limited trials, increased survival and quality of life in ICU survivors, changing prognostic factors, early ICU admission for optimal monitoring, and use of noninvasive diagnostic and therapeutic strategies. In this review, experts in the management of critically ill cancer patients highlight recent changes in the use and the results of intensive care in patients with malignancies. They seek to put forward a standard of care for the management of these patients and highlight important updates that are required to care for them. The research agenda they suggest includes important studies to be conducted in the next few years to increase our understanding of organ dysfunction in this population and to improve our ability to appropriately use life-saving therapies or select new therapeutic approaches that are likely to improve outcomes. This review aims to provide more guidance for the daily management of patients with cancer, in whom outcomes are constantly improving, as is our global ability to fight against what is becoming the leading cause of mortality in industrialized and non-industrialized countries.

The intensive care medicine research agenda on septic shock.

Septic shock remains a global health challenge with millions of cases every year, high rates of mortality and morbidity, impaired quality of life among survivors and relatives, and high resource use both in developed and developing nations. Care and outcomes are improving through organisational initiatives and updated clinical practice guidelines based on clinical research mainly carried out by large collaborative networks. This progress is likely to continue through the collaborative work of the established and merging trials groups in many parts of the world and through refined trial methodology and translational work. In this review, international experts summarize the current position of clinical research in septic shock and propose a research agenda to advance this field.

Intensive care medicine research agenda on cardiac arrest.

Over the last 15years, treatment of comatose post-cardiac arrest patients has evolved to include therapeutic strategies such as urgent coronary angiography with percutaneous coronary intervention (PCI), targeted temperature management (TTM)-requiring mechanical ventilation and sedation-and more sophisticated and cautious prognostication. In 2015, collaboration between the European Resuscitation Council (ERC) and the European Society for Intensive Care Medicine (ESICM) resulted in the first European guidelines on post-resuscitation care. This review addresses the major recent advances in the treatment of cardiac arrest, recent trials that have challenged current practice and the remaining areas of uncertainty.

Intensive care medicine research agenda on invasive fungal infection in critically ill patients.

To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenic patients in the ICU setting. A systematic review of the medical literature taking account of national and international guidelines and expert opinion. Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients. Approximately 80% of IFIs are due to Candida spp. and 0.3-19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1→3-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed.

The status of intensive care medicine research and a future agenda for very old patients in the ICU.

The "very old intensive care patients" (abbreviated to VOPs; greater than 80years old) are probably the fastest expanding subgroup of all intensive care unit (ICU) patients. Up until recently most ICU physicians have been reluctant to admit these VOPs. The general consensus was that there was little survival to gain and the incremental life expectancy of ICU admission was considered too small. Several publications have questioned this belief, but others have confirmed the poor long-term mortality rates in VOPs. More appropriate triage (resource limitation enforced decisions), admission decisions based on shared decision-making and improved prediction models are also needed for this particular patient group. Here, an expert panel proposes a research agenda for VOPs for the coming years.

The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship.

To concisely describe the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to the management of multidrug-resistant (MDR) bacteria, antibiotic use, and antimicrobial stewardship in the intensive care unit (ICU) setting. Narrative review based on a systematic analysis of the medical literature, national and international guidelines, and expert opinion. The prevalence of infection of critically ill patients by MDR bacteria is rapidly evolving. Clinical studies aimed at improving understanding of the changing patterns of these infections in ICUs are urgently needed. Ideal antibiotic utilization is another area of uncertainty requiring additional investigations aimed at better understanding of dose optimization, duration of therapy, use of combination treatment, aerosolized antibiotics, and the integration of rapid diagnostics as a guide for treatment. Moreover, there is an imperative need to develop non-antibiotic approaches for the prevention and treatment of MDR infections in the ICU. Finally, clinical research aimed at demonstrating the beneficial impact of antimicrobial stewardship in the ICU setting is essential. These and other fundamental questions need to be addressed over the next decade in order to better understand how to prevent, diagnose, and treat MDR bacterial infections. Clinical studies described in this research agenda provide a template and set priorities for investigations that should be performed in this field.

THE FOREIGN SOCRATIC INTENSIVE CARE MEDICINE CURRICULA

European Intensive Care Medicine (ICM) trainees and young specialists daily face the distinct local differences that exist in the minimum knowledge, skills, duration of training and non-technical behaviours which define a specialist. While ICM can be recognised as a 'particular competence' for those who have completed the appropriate training in most European countries, consistent heterogeneity may affect the potential to perform ICM research and to move across Europe.

Chlorhexidine-Based Oral Care and Ventilator-Associated Pneumonia

Ventilator-associatedpneumonia (VAP) is amongthemost frequently occurring infections among critically ill patients, and its development is associatedwith poor patient prognosis. As such, VAP has been an important topic of clinical research in intensivecaremedicine,pulmonology, infectiousdiseases, and clinicalmicrobiology. Yet, aftermore than 30 years of clinical studies on diagnosis, treatment, and prevention, a myriad of uncertainties remain. Among the many challenges that confront our efforts to effectively treat VAP is that there is currently no reliable gold standard fordiagnosis.Diagnosis is essentiallybasedonacombinationof clinical symptoms,microbiological test results, and radiological interpretations. These criteria, even in combination, are highly subjective and have suboptimal specificity. Subjective diagnosis of VAP hampers unbiased evaluation of the efficacy of preventive measures in unblindedstudies and increases the riskof assessmentbiaswhen VAP rates are used as a quality metric. Poor specificity of the diagnosis leads to unnecessary antibiotic use and its associatedharms.Ofnote, thediagnostic approachwithbetter specificity, ie, bronchoscopic procedures combinedwith quantitative microbiological cultures, is hardly used because it is invasive and expensive. The other sizable challenge in VAP management is that the evidence for preventive strategies is less robust than it appears on first examination. For instance, most guidelines recommend semirecumbent patient positioning. However, this recommendation is based on a prematurely interrupted controlled trial of 87 patients, in which the beneficial effects of the semirecumbent position could not be separated from the detrimental effects of continuous gastric feeding in control patients randomized to a complete supine position.1 The only other randomized trial of this intervention in intensive care unit (ICU) patients questioned the feasibility of the 45° position and failed to demonstrate a benefit from the 30° position.2 Some guidelines also recommend topical antimicrobial prophylaxis, such as selective decontamination of the digestive tract andselectiveoropharyngealdecontamination.These treatments have been associatedwith statistically significant reductions in the incidence of VAP inmany randomized trials and with improved patient outcome in settings with low levels of antibiotic resistance.3 Yet, absence of evidence of benefit in settings with higher levels of antibiotic resistance and fear of selection for antibiotic resistancehavepreventedwidespread adoption of these measures. There is greater consensus for theuseof chlorhexidinegluconate oropharyngeal care as a strategy for VAP prevention, in part because of its perceived safety, both for individual patients andwith respect to avoiding antibiotic resistance.However, althoughchlorhexidine iswidelyusedandhasbeen identified as an important process of high-quality care by the Institute forHealthcare Improvement, theevidence that it prevents VAP or improves patient outcome isweaker than for selective decontamination. In this issue of JAMA Internal Medicine, Klompas and coworkers4 question the effectiveness and safetyof chlorhexidineoral care inpatients receivingmechanicalventilation inthe ICU. This conclusion is based on the results of a new metaanalysis of 16 randomized trials evaluating this intervention in 1868 cardiosurgical patients (3 studies) and 1762 intensive care patients (13 studies).This stratifiedmeta-analysis suggests that chlorhexidine oral care is effective in cardiosurgery patients, whogenerallyundergo intubationandventilationonly forshort periodsaftersurgery,butnotamongintensivecarepatients,who generally undergo intubation for a longer period. In the intensive care patients, the authors found only statistically nonsignificanteffectsonthepreventionofVAP; inopen-label trials the summary risk ratio (RR) was 0.61 (95% CI, 0.35-1.04) and in double-blind trials the RR was 0.88 (95% CI, 0.66-1.16). Furthermore, there was a statistically nonsignificant result of increasedmortalityamong intensivecarepatients randomized to receivechlorhexidineoralcare(RR,1.13[95%CI,0.99-1.29]),with some evidence of a dose-response effect. Related article page 751 Chlorhexidine Oral Care andMechanical Ventilation Original Investigation Research

Models for Intensive Care Training. A European Perspective

The diversity of European culture is reflected in its healthcare training programs. In intensive care medicine (ICM), the differences in national training programs were so marked that it was unlikely that they could produce specialists of equivalent skills. The Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) program was established in 2003 as a Europe-based worldwide collaboration of national training organizations to create core competencies for ICM using consensus methodologies to establish common ground. The group's professional and research ethos created a social identity that facilitated change. The program was easily adaptable to different training structures and incorporated the voice of patients and relatives. The CoBaTrICE program has now been adopted by 15 European countries, with another 12 countries planning to adopt the training program, and is currently available in nine languages, including English. ICM is now recognized as a primary specialty in Spain, Switzerland, and the UK. There are still wide variations in structures and processes of training in ICM across Europe, although there has been agreement on a set of common program standards. The combination of a common "product specification" for an intensivist, combined with persisting variation in the educational context in which competencies are delivered, provides a rich source of research inquiry. Pedagogic research in ICM could usefully focus on the interplay between educational interventions, healthcare systems and delivery, and patient outcomes, such as including whether competency-based program are associated with lower error rates, whether communication skills training is associated with greater patient and family satisfaction, how multisource feedback might best be used to improve reflective learning and teamworking, or whether increasing the proportion of specialists trained in acute care in the hospital at weekends results in better patient outcomes.