Newsletter July 2023: ESAIC and BJA Foundation-ESAIC Grants Winners 2023 – learn about the four funded projects

The European Society of Anaesthesiology and Intensive Care (ESAIC) and the British Journal of Anaesthesia Foundation (BJA Foundation) have a long-standing collaboration to support and promote research excellence in the field of anaesthesia. One of the outcomes of this partnership is the BJA Foundation – ESAIC Grant, which aims to enhance clinical practice and foster innovation among early career researchers. 

This year (2023), the BJA Foundation – ESAIC Grant awarded two grants of 60,000 EUR each to two outstanding projects within the framework of anaesthesia. The winners were selected from a pool of 40 applicants who submitted full proposals after a rigorous peer-review process carried out by the BJA Foundation – ESAIC Steering Committee. 

In addition, the ESAIC also granted two other awards to early career researchers: the ESAIC Andreas Hoeft Grant (60,000 EUR) dedicated to intensive care, and the ESAIC Research Project Grant (50,000 EUR) dedicated to anaesthesiology. These grants were also highly competitive and attracted many high-quality applications. 

This article consists of four smaller articles, each covering the grant winners and their respective projects. The projects span diverse topics and methods in the field of anaesthesia and intensive care.  

BJA Foundation – ESAIC Grant winner (€60,000): Pascal Smulders  (Netherlands)

Analgesic Effects of Dexamethasone in Regional Anaesthesia: Back to the Electrophysiological Basics in a Human-Induced Pluripotent Stem Cell Model

Pascal SH Smulders, Nina C Weber, Werner ten Hoope, Arie O Verkerk, Jeroen Hermanides, Markus W Hollmann 

Dexamethasone is an effective glucocorticoid drug used in peripheral regional anaesthesia. Yet, although systematic reviews and meta-analyses have demonstrated the block-prolonging effects of the perineural injection of dexamethasone, controversy remains over its efficacy.1-4 Specifically, debate continues over the existence of a peripheral mechanism of action of dexamethasone. Previously, however, we found that perineural dexamethasone strongly inhibits the electrical activity of human nociceptive dorsal root ganglion neurons differentiated from human induced pluripotent stem cells.  

In this follow-up project, we build on this model and aim to further unravel the molecular mechanism behind this effect. We hypothesise that dexamethasone exerts its effects through a dynamic modulatory action on potassium channel expression and apply laboratory assays to evaluate all steps of protein biosynthesis. 

References

1. Albrecht E, Kern C, Kirkham KR. A systematic review and meta-analysis of perineural dexamethasone for peripheral nerve blocks. Anaesthesia. 2015;70(1):71-83. 
2. Xuan C, Yan W, Wang D, et al. The Facilitatory Effects of Adjuvant Pharmaceutics to Prolong the Duration of Local Anesthetic for Peripheral Nerve Block: A Systematic Review and Network Meta-analysis. Anesth Analg. 2021;133(3):620-629. 
3. Choi S, Rodseth R, McCartney CJ. Effects of dexamethasone as a local anaesthetic adjuvant for brachial plexus block: a systematic review and meta-analysis of randomised trials. Br J Anaesth. 2014;112(3):427-439. 
4. Pehora C, Pearson AM, Kaushal A, Crawford MW, Johnston B. Dexamethasone as an adjuvant to peripheral nerve block. Cochrane Database Syst Rev. 2017;11:CD011770.

BJA Foundation – ESAIC Grant winner (€60,000): Christoph Dibiasi (Austria)

Is anti-factor Xa activity associated with venous thromboembolic events in critically ill patients receiving enoxaparin for pharmacological thromboprophylaxis?

Christoph Dibiasi

Venous thromboembolism (VTE) occurs in about 10% of all patients admitted to an intensive care unit (ICU) 1 and is related to prolonged ICU stays and increased mortality 2. Appropriate pharmacological thromboprophylaxis, usually with low molecular weight heparin (LMWH), is crucial for preventing VTE. It has been suggested that low anti-factor Xa activity (anti-Xa) is associated with “breakthrough” VTE in patients receiving LMWH for thromboprophylaxis, but only low-quality evidence supports this claim 3. Currently, there is a lack of evidence on appropriate antiXa target ranges for thromboprophylaxis in critically ill patients. Furthermore, it remains unclear whether antiXa in the context of thromboprophylaxis is associated with developing VTE in the ICU at all 4. 

We, therefore, designed a prospective, observational multicentre trial to address this question. We plan to include critically ill patients who receive prophylactically dosed enoxaparin. Important exclusion criteria are therapeutic anticoagulation, VTE at admission or extracorporeal membrane oxygenation. We will measure peak and trough anti-Xa daily until the development of VTE, death, ICU discharge or for a maximum of 14 days. We will record all symptomatic VTE and screen included patients for asymptomatic deep vein thrombosis once per week using ultrasonography. 

The results of our study will clarify whether low antiXa is associated with VTE and whether there is an antiXa range that may be protective from VTE in critically ill patients. We furthermore aim to analyse whether antiXa is associated with bleeding. 

References

1. Gao X, Zeng L, Wang H, et al. Prevalence of Venous Thromboembolism in Intensive Care Units: A Meta-Analysis. J Clin Med Multidisciplinary Digital Publishing Institute; 2022; 11: 6691  
2. Lewis TC, Cortes J, Altshuler D, Papadopoulos J. Venous Thromboembolism Prophylaxis: A Narrative Review With a Focus on the High-Risk Critically Ill Patient. J Intensive Care Med 2019; 34: 877–88  
3. Gratz J, Wiegele M, Dibiasi C, Schaden E. The challenge of pharmacological thromboprophylaxis in ICU patients: anti-FXa activity does not constitute a simple solution. Intensive Care Med 2022; 48: 1116–7  
4. Vahtera A, Vaara S, Pettilä V, Kuitunen A. Plasma anti-FXa level as a surrogate marker of the adequacy of thromboprophylaxis in critically ill patients: A systematic review. Thromb Res 2016; 139: 10–6  

ESAIC Research Grant Winner: Andreas Hoeft’s Grant (€60,000) – Maximilian Dietrich  (Germany)

Machine Learning assisted early diagnosis of sepsis based on microcirculatory alterations in ICU patients

Maximilian Dietrich, Stephan Katzenschlager, Silvia Seidlitz, Katharina Hölzl, Ayca Von Garrel, Felix C.F. Schmitt, Lena Maier-Hein, Markus A. Weigand, Tobias Hölle

Sepsis is one of the most important medical challenges, causing 11 million deaths yearly.1 An immediate diagnosis and subsequent therapy start are crucial for survival. The early stage of sepsis often remains unrecognised due to its unspecific symptoms. 

Microcirculatory alterations are key mechanisms in sepsis pathophysiology and correlate with organ failure and mortality.2 Therefore, capillary refill time is widely established for clinical evaluation. However, no objectifiable technical method to assess microcirculation is implemented as a standard of care in intensive care medicine. 

Hyperspectral Imaging (HSI) uses various substances’ specific light reflection and absorption properties to calculate tissue oxygenation, haemoglobin and water content in real-time from a single non-invasive image.3  

In a pilot study, we used HSI to visualise a microcirculatory pattern in septic patients: reduced skin oxygenation, increased haemoglobin pooling and increased tissue water content.4 Based on these HSI skin images, we implemented a Machine Learning (ML) algorithm to differentiate septic patients from postoperative patients and healthy volunteers. However, we also revealed confounding factors that could lead to overestimating the algorithm’s performance.5 

This study aims to confirm the potential of ML for automated sepsis detection based on HSI. To this end, all patients treated in the interdisciplinary surgical intensive care unit of the Heidelberg University Hospital are enrolled. HSI images of the patient’s palms are recorded, and patients are classified as septic or non-septic once a day for one year. In addition, metadata for potential confounding factors is acquired. An ML algorithm will be trained and validated to identify sepsis based on hyperspectral skin images.  

References

1. Rudd K, Johnson S, Agesa K, et al. Lancet 2020;395(10219):200-211 
2. De Backer D, Ricottilli F, Ospina-Tascón G. Curr Opin Anaesthesiol 2021;34(2):85-91 
3. Holmer A, Tetschke F, Marotz J, et al. Physiol Meas 2016;37(11):2064-2078.  
4. Dietrich M, Marx S, von der Forst M, et al. Microvasc Res 2021;136:104164 
5. Dietrich M, Seidlitz S, Schreck N, et al. ArXiv, abs/2106.08445. 

ESAIC Research Grant Winner: Research Project Grant (€50,000) – Gertrude Nieuwenhuijs-Moeke (Netherlands)

Refurbished Organs; a call for anaesthetic expertise

Gertrude J Nieuwenhuijs-Moeke

Machine perfusion (MP) is an emerging multidisciplinary (research) field in organ transplantation and has shown superiority over the classically used static cold storage (SCS) for various organs in clinical trials.1-3 In contrast to SCS, MP allows assessment of the viability and functionality of the graft to be, to reduce the discard of potentially good organs.4,5 Moreover, MP enables extending the preservation period facilitating logistics concerning the transplant procedure.6 But most exciting, MP provides a therapeutic window of opportunity to reduce injury, enhance repair and improve the quality of potential donor organs, facilitating further reduction of discard, enhancement of the donor pool and improvement of transplant outcomes.7 In this perspective, anaesthesiologic knowledge on (patho)physiology of injurious phenomena, like ischemia-reperfusion injury (IRI) and inflammation, and pharmacological strategies to intervene are definitely of added value.8-10 With our broad expertise in (measurement of) haemodynamics and organ perfusion, our role is highly complementary to existing knowledge, contributing to MP reaching its full therapeutic potential.10 With the current VITALISE project, supported by the ESAIC research grant, we hope to improve the quality of the donor’s lungs by ventilating the lungs with sevoflurane during ex vivo lung perfusion (EVLP). In our first step, the pilot project, we’ve shown that ventilating lungs with sevoflurane during EVLP is feasible and results in improved dynamic lung compliance. Anaesthesiology should seize the opportunity to contribute to the expanding field of MP and join forces with other specialities to improve the outcome of our patients. 

References

1. Moers C, Smits JM, Maathuis MH et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):7-19.  
2. van Rijn R, Schurink IJ, de Vries Y et al. Hypothermic Machine Perfusion in Liver Transplantation – A Randomised Trial. N Engl J Med. 2021;384(15):1391-1401.  
3. Jochmans I, Brat A, Davies L, et al. Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial. Lancet. 2020;396(10263):1653-1662.  
4. Mergental H, Laing RW, Kirkham AJ et al. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nat Commun. 2020;11(1):2939.  
5. Boffini M, Ricci D, Bonato R, et al. Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion. Eur J Cardiothorac Surg. 2014 Nov;46(5):789-93. 

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