Preckel B.: Patient safety, procedural sedation, cardiovascular protection

1. Cardioprotection This is one the key aspects of research activities at L.E.I.C.A. Cardioprotective actions of anesthetics (e.g. volatile anesthetics, opiates, noble gases) are evaluated under various experimental conditions for their effectiveness and mechanisms of action.

A. Role for Caveolin- Cytoskeleton and Exosomes in Helium induced Organ Protection?
Helium induces profound protection against ischemia-reperfusion in animals and humans. However, only sparse data are available regarding a possible molecular mechanism of this protection.
Caveolins, structural scaffolding proteins, allow for organization of signalling molecules in caveolae, membrane invaginations enriched in lipids. Caveolin-3 (Cav-3) is a heart specific isoform that is modulated by volatile anesthetics and is required for cardiac protection. As Caveolins are closely related to the cytoskeleton we aim to investigate the role of these proteins, there binding partners and the cytoskeleton in Helium induced organ protection. (Project led by Dr. N.C. Hauck-Weber) Grants: Society of Cardiovascular Anesthesiologists (SCA), Cooperation with the University of San Diego, Department of Anesthsiology, Professor HH Patel

B. Organ protection by helium in human tissue
The capacity to induce preconditioning with helium could be useful for patients subjected to inevitable organ ischemia; e.g. during vascular surgery, organ transplantation, cardiac surgery. Helium organ protection is investigated in clinical settings as well as in studies several studies in volunteers, to translate the findings from the laboratory to the clinical setting. HUVEC (Human Umbilical Vein Endothelial Cells) are frequently used as an in vitro model for investigations on endothelial cell damage. Vascular endothelial cells form the inner lining of all blood vessels. Programmed cell death of these cells, called apoptosis, plays a major role in the development and progression of common cardiovascular diseases like atherosclerosis and is also involved in tissue damage after myocardial ischemia. We investigate whether preconditioning with helium reduces apoptosis in HUVEC by measuring expression of adhesion molecules and different apoptotic markers in both adherent cells and in microparticles in collaboration with the laboratory of experimental clinical chemistry (LEKC) of the AMC.
Gas embolism, defined as the entry of gas into vascular structures, can occur in many clinical environments as an iatrogenic complication and in diving medicine. In most cases gas embolism is in fact an air embolism, although the medical use of other gases (such as carbon dioxide) can also result in this condition. Air bubbles may reach any organ, but their effect on the cerebral and cardiac circulation is particularly deleterious because these organs are highly vulnerable for hypoxia. Hyperbaric oxygen therapy has been advocated as a therapy for gas embolism, whereby the patient breathes 100% oxygen at a pressure above that of the atmosphere at sea level. Helium might be an alternative to treat or even prevent development of gas embolism. In close cooperation with the Diving Medical Center, Royal Netherlands Navy, we investigate the effects of helium in animal models of cerebral air embolism. C. Remote Ischaemic Pre-Conditioning
Remote ischaemic preconditioning (RIPC) by repeated short periods of limb ischaemia using a tourniquet protects against ischaemia/reperfusion damage after surgery. The serum taken from volunteers and also animals therefore might contain several potentially protective factors which are investigated in an in vitro model of HUVEC and other cells. Here we also are interested in a possible role for Caveolin. (Co-operation with the University of Kiel, Priv.-Doz. Dr. Martin Albrecht, Professor Dr. Berthold Bein, Project led by Dr. N.C. Hauck-Weber). In clinical studies, we investigate the outcome and molecular basis for Remote Conditioning in humans 2. Optimizing Therapy in Perioperative Diabetes Mellitus
Patients with Diabetes mellitus (DM) have increased risks for complications during the preioperative period. We investigate the incidence of intraoperative hyperglycaemia and its complications, factors leading to perioperative hyperglycaemia, the effects of glucose variability on perioperative outcome, hyperglycaemia and hypoglycaemia in the ICU and the OR measured by continuous subcutaneous glucose sensors. The benefits of new anti-diabetic drugs (GLP-1 inhibitors) during the perioperative period are investigated in a multicenter RCT.
Another important aspect of our research is the protection of the diseased animal by conditioning, e.g. in experimental models of diabetes and hypertension we have investigated the effectiveness of helium induced cardioprotection.

3. Perioperative patient safety
A Patient-Safety Board of Anesthesiology has been instituted to implement tools for improving safety issues during the perioperative process, e.g. effects of Emergency Cards and Cognitive Aids in the OR as well as on the ward, the possibility of nation wide constant drug labeling in anesthesia departments, adequacy of analgesia during surgery, and quality and use of standard operating procedures.
We also investigate the safety and improvements of non-anesthesiologist induced sedation. In the health care system, non-physicians will more and more take over responsibility for routine practices that are currently namely performed by physicians. We will explore the risks and benefits for the society of this shift of responsibility.
Fluid management and goal directed therapy in patients subjected to major non-cardiac surgery as well as microcirculation during transthoracic esophageal cardia resections is studied using sophisticated non-invasive hemodynamic monitoring. In cardiac surgery, accuracy of advanced non-invasive hemodynamic monitoring is determined.