Dutch Anaesthesia Research Showcase Abstracts 16e Wetenschapsdag anesthesiologie

Transcriptie

1 volume 32 September 2019 Dutch Anaesthesia Research Showcase Abstracts 16e Wetenschapsdag anesthesiologie Keynote speaker: Hugh C. Hemmings 3 Thema s: Clinical & Experimental Circulation Pain & Palliative Care Pulmonary Physiology/ Gas Exchange Central Nervous System Perioperative Medicine Pharmacology Laat zien wat je in huis hebt! Officiële uitgave van de Nederlandse Vereniging voor Anesthesiologie Hoofdredactie: Dr. P. A. van Beest & Dr. R.V. Immink

2 COLOFON Inleiding Het Nederlands Tijdschrift voor Anesthesiologie is het officiële orgaan van de Nederlandse Vereniging voor Anesthesiologie. Het stelt zich ten doel om door middel van publicatie van overzichtsartikelen, klinische en laboratoriumstudies en casuïstiek, de verspreiding van kennis betreffende de anesthesiologie en gerelateerde vakgebieden te bevorderen. Redactie Hoofdredactie: Dr. P. A. van Beest & Dr. R.V. Immink Redacteuren: Dr. J. Bijker, Dr. A. Bouwman, Dr. P. Bruins, Prof. Dr. A. Dahan, Dr. S. Dieleman, Dr. H. van Dongen, Dr.L.van Eijk, Dr. J.P. Hering, Prof. Dr. M.W. Hollmann, Dr. J.S. Jainandunsing, Prof. Dr. E.A.E. Joosten, Dr. M. Klimek, Dr. A. Koopman, Dr. F. Van Lier, Prof. Dr. S.A. Loer, Prof. Dr. B. Preckel, Prof. Dr. G.J. Scheffer, Dr. M.F. Stevens, Dr. B. in t Veld, Dr. M. van Velzen, Prof. Dr. K. Vissers. Voor informatie over adverteren en het reserveren van advertentieruimte in het Nederlands Tijdschrift voor Anesthesiologie: Eventex T sales@eventex.nl Redactie-adres Nederlandse Vereniging voor Anesthesiologie Domus Medica, Mercatorlaan 1200, 3528 BL Utrecht; Inzenden van kopij Richtlijnen voor het inzenden van kopij vindt u op of kunt u opvragen bij de NVA, ntva@anesthesiologie.nl Oplage exemplaren, 4x per jaar Het NTvA wordt uitsluitend toegezonden aan leden van de NVA. Adreswijzigingen: Nederlandse Vereniging voor Anesthesiologie, Postbus 20063, 3502 LB Utrecht, T , F , nva@anesthesiologie.nl Productie Ontwerp: Stefan de Rooij - Secrass GRAFISCH Druk: Secrass GRAFISCH Eindredactie & bladcoördinatie: Sandra Gijtenbeek-NVA Huub van Workum - Eventex Auteursrecht en aansprakelijkheid Nederlands Tijdschrift voor Anesthesiologie is een wettig gedeponeerd woordmerk van de Nederlandse Vereniging voor Anesthesiologie. Alle rechten voorbehouden. Niets uit deze uitgave mag worden verveelvoudigd, opgeslagen in een geautomatiseerd gegevensbestand of openbaar gemaakt, in enige vorm of op enige wijzen, hetzij elektronisch, mechanisch, door fotokopieën, opnamen of enige andere manier, zonder voorafgaande schriftelijke toestemming. LAAT ZIEN WAT JE IN HUIS HEBT! Wetenschapsdag anesthesiologie op vrijdag 4 oktober Dit is kort door de bocht het verzoek geweest aan de opleidingsklinieken (met de geaffilieerde opleidingsziekenhuizen) in Nederland. Alle 9 opleidingsziekenhuizen hebben hier gehoor aan gegeven en leverden drie presentaties in, twee van 10 minuten en een van 20, om hiermee hun beste recente wetenschappelijke werk te presenteren in een Dutch Anaesthesia Research Showcase. Wij hebben de presentaties zo veel mogelijk thematisch gegroepeerd (pijn/palliatieve zorg, outcomes, perioperative medicine, circulation, pharmacology, etc.). De voertaal van de presentaties en discussies is Engels. De abstracts van de oral presentations worden gepubliceerd in het oktobernummer van NTvA. De abstracts van de posters worden gepubliceerd in het decembernummer. We zijn trots dat hij speciaal voor ons naar Utrecht wil komen: prof. Hugh Hemmings, hoofd van de afdeling anesthesiologie van Cornell University in New York en Editorin-Chief van het anesthesiologische topblad British Journal of Anaesthesia. Hij gaat niet alleen spreken over zijn wetenschappelijke passie, het ontrafelen van de werkingsmechanismen van anesthetica, maar ook over de vele dilemma s die optreden bij het combineren van anesthesiologische klinieken, wetenschap en management. Het charmante theater Het Huis Utrecht is de locatie van deze wetenschapsdag. Dit theater kan 250 bezoekers ontvangen. Vanaf station Utrecht CS is het circa 10 minuten lopen naar het gebouw en in de omgeving zijn meerdere grote parkeergarages. Voor degenen die na de meeting nog willen napraten of dineren is er in de buurt (het oude stadscentrum van Utrecht) ruime keus uit goede horeca. Wij zien er naar uit! U ook? Meld u dan aan via de website van de NVA. 4 oktober 2019 Cor Kalkman Reinier Hoff Wilton van Klei Abstracts wetenschapsdag

3 Programma Wetenschapsdag 4 oktober 2019 programma Ontvangst Welkom en opening door prof. Wilton van Klei Clinical & Experimental Circulation (1) Aprotinin reduces renal edema, but does not preserve renal perfusion and function following cardiopulmonary bypass in rats N.A.M. Dekker, A.L.I. van Leeuwen, A.B.A. Vonk, C. Boer, C.E. van den Brom Amsterdam UMC locatie VUmc Remote ischaemic preconditioning and postoperative myocardial injury in patients undergoing pancreatic surgery: a randomised controlled trial L. van Zeggeren, R.A. Visser, I.M. Dijkstra M. Bosma, H.C. van Santvoort, P.G. Noordzij St. Antonius Ziekenhuis Perioperative Outcomes The impact of decreased skeletal muscle mass on short term outcome after abdominal aortic aneurysm repair R.M. Smoor, S. Brouwers, H.P.A. van Dongen, R. Kropman, P.G. Noordzij St. Antonius Ziekenhuis Wireless Vital Signs Monitoring Using Wearable Sensors in Patients at the Step Down Unit and Surgical Ward: a Clinical Validation Study M. Breteler, E. KleinJan, T. Blokhuis, R. van Hillegersberg, J. Ruurda, K. van Loon, L. Leenen, C. Kalkman Universitair Medisch Centrum Utrecht Early postoperative data: relevance and future perspectives for the Anesthesiologist V.G.B. Liem, S.E. Hoeks, K.H.J.M. Mol, R.J. Stolker, F. van Lier Erasmus MC Physicians opinions regar ding anticoagulant therapy in patients with a limited life expectancy B.A.A. Huisman,, E.C.T. Geijteman, N. Kolf, M.K. Dees, L. van Zuylen, K.M. Szadek, M.A.H. Steegers, A. van der Heide Amsterdam UMC locatie VUmc Pauze Clinical & Experimental Circulation (2) Association between postoperative myocardial injury phenotypes and disability-free-survival in patients undergoing non-cardiac surgery L.M. Vernooij, J.A. van Waes, M. McKenny, M. Machina, S. Feng, D.N. Wijeysundera, H.M. Nathoe, L.M. Peelen, W.A. van Klei, W. Scott Beattie Universitair Medisch Centrum Utrecht Non-invasive oscillometric versus invasive arterial blood pressure measurements in critically ill patients T. Kaufmann, E.G.M. Cox, R. Wiersema, B. Hiemstra, T.W.L. Scheeren, B. Saugel, I.C.C. van der Horst Universitair Medisch Centrum Groningen Use of a machine-learning algorithm in combination with treatment guidance reduces hypotension during surgery: a randomized clinical trial M. Wijnberge, B.F. Geerts, L. Hol, N. Lemmers, M.P. Mulder, P. Berge, J. Schenk, L.E. Terwindt, M.W. Hollmann, A.P. Vlaar, D.P. Veelo Amsterdam UMC locatie AMC Abstracts wetenschapsdag

4 Pain & Palliative Care (1) Magneto-encephalography to image the effects of chronic pain and Spinal Cord Stimulation Bart Witjes, Mathieu Roy, Elizabeth Bock, Robert Oostenveld, Frank Huygen, Sylvain Baillet, Cecile de Vos Erasmus MC Alternatives to the classical opioid analgesics characterized by utility functions to determine toxicity versus safety H. Algera, E. Olofsen, M. van Velzen, M. Niesters, L. Aarts, A. Dahan Leids Universitair Medisch Centrum Genome-wide association analysis identifies potential risk loci for chronic postsurgical pain R.I. van Reij, D.M.N. Hoofwijk, B.P.F. Rutten G. Kenis, M. Theunissen, L. Weinhold, M. Leber, M. Knapp, S. Heilmann-Heimbach, M.M. Nöthen, P. Hoffman,M. Schmid, M. Allegri, G. Cappelleri, M. De Gregori, W.F.F.A. Buhre, E.A.J. Joosten, A. Ramirez, N.J. van den Hoogen Maastricht UMC KEYNOTE: Unraveling the synaptic mechanisms of general anesthetics prof. Hugh Hemmings Weill Cornell Medicine Medical College, NY Influence of reversal of a partial neuromuscular block on the ventilatory response to hypoxia: a randomized controlled trial in healthy volunteers M. Boon, S.J.L. Broens, Ch.H. Martini, M. Niesters, M. van Velzen, L.P.H.J. Aarts, A. Dahan Leids Universitair Medisch Centrum Central Nervous System The Influence of Blood Pressure on Cerebral Autoregulation Efficacy during Propofol and Sevoflurane Anaesthesia R.E.C. van den Dool, R.V. Immink, J. Hermanides, M.W. Hollmann, N.H. Sperna Weiland Amsterdam UMC locatie AMC Assessing CO2 toxicity in rat and man: a translational study identifying the effects of high levels of inspired CO2 on cardiorespiratory physiology R. van der Schrier, E. Olofsen, M. van Velzen, M. Niesters, L. Aarts, A. Dahan Leids Universitair Medisch Centrum The BRAIN-PROTECT study on prehospital treatment of severe TBI: Study design and first results S.M. Bossers (on behalf of the BRAIN PROTECT collaborators) Amsterdam UMC locatie VUmc Lunchpauze Posters (walkarounds; presenters in attendance) Pulmonary Physiology/Gas Exchange Positive end-expiratory pressure affects the position and function of the human diaphragm D. Jansen, A.H. Jonkman, H.J. de Vries, C. Keijzer, A.R.J. Girbes, T. Marcus, C.A.C. Ottenheijm, L.M.A. Heunks Radboudumc The Anaesthetic Biobank of Cerebrospinal Fluid - methods and baseline results C. Tigchelaar, S.D. Atmosoerodjo, R. Absalom Universitair Medisch Centrum Groningen Pauze Perioperative Medicine Emergency front- of- neck- airway (efona). Perspectives on preparedness, training and clinical practice L.A. Bruijstens, on behalf of all co-authors for individual studies Radboudumc Abstracts wetenschapsdag

5 Programma Wetenschapsdag 4 oktober 2019 programma MRI measurement of the effects of moderate versus deep neuromuscular blockade on the abdominal working space during laparoscopic donor nephrectomy P. Krijtenburg, M.H.D. Bruintjes, G.J. Scheffer, C. Keijzer, M.C. Warlé Radboudumc Mitochondria: Gaining insight in our (damaged) allies E.G. Mik ErasmusMC Pharmacology Closed-Loop Spinal Cord Stimulation: A basic explanation of the operating principals of a novel stimulation paradigm J.W. Kallewaard, H. Nijhuis, J.L. Parker Rijnstate/UMCU The impact of metamizol on kidney function and pain therapy outcome after cardiothoracic surgery: a prospective observational non-inferiority cohort study A.M. den Ouden, N.H.Th. Voesten, L. Timmerman, H. Kelder, C.A.J. Knibbe, H.J. Blussé van Oud-Alblas St. Antonius Ziekenhuis Optimaliseren en individualiseren van medicatietoediening middels het toepassen van pharmacokinetische en -dynamische (PKPD) kennis J.P. van den Berg, H.E.M. Vereecke, M.M.R.F. Struys Universitair Medisch Centrum Groningen Liraglutide for perioperative management of hyperglycemia in cardiac surgery patients: a multicenter randomized superiority trial A.H. Hulst, M.J. Visscher, M.B. Godfried, B. Thiel, B.M Gerritse, Th.V. Scohy, R.A. Bouwman, M.G.A. Willemsen, M.W. Hollmann, B. Preckel, J. de Vries, J. Hermanides, on behalf of the GLOBE study group Amsterdam UMC locatie AMC PRediction of Opioid-induced respiratory Depression In patients monitored by capnography. of the PRODIGY trial J.D. de Korte-de Boer Maastricht UMC Update Young Investigator Grant: Repair of capillary perfusion and prevention of kidney damage during haemorrhagic shock Charissa van den Brom, Amsterdam UMC locatie VUmc Prijsuitreiking - afsluiting Uitslag stemmen en prijsuitreiking Borrel en einde dag Pain & Palliative Care (2) Dorsal Root Ganglion Stimulation in Experimental Painful Diabetic Peripheral Neuropathy G. Franken, J. van Zundert, E.A. Joosten Maastricht UMC+ Abstracts wetenschapsdag

6 Keynote Speaker UNRAVELING THE SYNAPTIC MECHANISMS OF GENERAL ANESTHETICS Hugh C. Hemmings, Jr., M.D., Ph.D. Editor in Chief British Journal of Anaesthesia Hugh Hemmings has a broad background in neuroscience, neuropharmacology and anesthesiology. He studied Biochemistry and Pharmacology at Yale University, and completed his PhD research in Pharmacology at the Yale Graduate School. He worked with Paul Greengard for his graduate and postdoctoral research at Yale and the Rockefeller University; this work was cited in Greengard s 2000 Nobel Prize in Physiology and Medicine. After Medical School, also at Yale University, he completed his Anesthesiology residency in 1991 at Massachusetts General Hospital, Boston, MA. Professor Hemmings is currently Professor and Chair of the Department of Anesthesiology at New York-Presbyterian Hospital/Weill Cornell Medical Center. He is also a Professor of Pharmacology at Weill Cornell Medical College as well as Senior Associate Dean for Research. As Chair of the Department of Anesthesiology, Dr. Hemmings oversees an extensive clinical and basic anesthesiology research program. He has authored over 160 publications, including a textbook on basic anesthesiology. His clinical practice focuses on anesthesia for thoracic surgery. He leads a successful research group investigating the neuropharmacology of general anesthetics, neuroprotection, cell signaling and novel analgesia therapies ( In 2018 he became Editor-in-Chief of British Journal of Anaesthesia. Abstracts wetenschapsdag

7 Prof. Hemmings main scientific interest is unraveling the mechanism of action of general anesthetics, because he views a better understanding of the mechanism of action of general anesthesia as a prerequisite for the development of safer and more specific anesthetics. Prof. Hemmings is a world expert in the effects of general anesthetics and mechanisms of neuronal signal transduction, and his team has made fundamental discoveries how general anesthetics affect synaptic transmission, both on the cellular and molecular levels. His research has been consistently supported by the US National Institutes of Health. Neuropharmacology and Cell Signaling There are two principal areas of research in prof. Hemmings laboratory: mechanisms of general anesthetic drugs and cell signaling. Anesthetics have potent and specific effects on synaptic transmission, including both presynaptic actions on the release of neurotransmitters and postsynaptic actions on their receptors: at clinically relevant concentrations, most general anesthetics depress excitatory synaptic transmission, while some, including propofol and barbiturates, facilitate inhibitory synaptic transmission. The pharmacology and toxicology of general anesthetics are remarkably incomplete for such a widely used and clinically important class of drugs. Our current understanding of the molecular and cellular mechanisms of general anesthetic action in the central nervous system is poor and insufficient to explain how any anesthetic produces amnesia, unconsciousness, or immobilization (with increasing doses). Electrophysiological evidence indicates that general anesthetics act primarily on synaptic transmission without major effects on axonal conduction or neuronal excitability. Prof. Hemmings research aims to understand the presynaptic mechanisms of anesthetic effects on neurotransmitter release. Understanding these mechanisms is essential for development of anesthetics with improved side-effect profiles and for optimization of current anesthetic techniques in high-risk patients. His lab s current focus is on the region- and transmitter-specific actions and Na+ channel blocking mechanisms of volatile anesthetics. Such studies are essential to a better molecular understanding of the balance between desirable and potentially toxic anesthetic effects on excitatory and inhibitory synaptic transmission. There is good evidence for both presynaptic and postsynaptic mechanisms for these effects, including presynaptic reductions in excitatory neurotransmitter release, inhibition of postsynaptic responses to excitatory neurotransmitters, and facilitation of postsynaptic responses to inhibitory neurotransmitters. However, the precise molecular mechanisms involved in these effects are unknown. Abstracts wetenschapsdag

8 Abstracts Clinical & Experimental Circulation (1) Clinical & Experimental Circulation (1) Aprotinin reduces renal edema, but does not preserve renal perfusion and function following cardiopulmonary bypass in rats N.A.M. Dekker 1,2, A.L.I. van Leeuwen 1,2,3, A.B.A. Vonk 3, C. Boer 1, C.E. van den Brom 1,2 1 Departments of Anesthesiology 2 Department of Physiology 3 of Cardiothoracic Surgery Experimental Laboratory for Vital Signs (ELVIS), Amsterdam Cardio vascular Sciences, UMC - location VUmc Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion, which is paralleled by microvascular leakage and associated with acute kidney injury. Thrombin is released during CPB, which leads to increased endothelial permeability. Aprotinin (Trasyslol), an anti-fibrinolytic, is suggested to inhibit thrombin/par1-induced endothelial hyperpermeability. Therefore, we investigated whether targeting the thrombin/par1 system using aprotinin reduces renal edema formation, preserves renal perfusion and reduces renal injury following CPB. Rats were subjected to 75 minutes of CPB after treatment with aprotinin (n=15) or PBS (n=15). Cremaster and renal microcirculatory perfusion were measured using intravital microscopy and contrast echography before CPB, and 10 and 60 minutes after weaning from CPB (post-cpb). Wet/dry weight ratios were determined from harvested kidney tissue. Plasma creatinine was measured by ELISA. Onset of CPB decreased hematocrit levels (39±3 to 22±2%, P<0.01) and blood pressure (88±15 to 73±9mmHg, P=0.02). CPB resulted in a 2-fold reduction in the number of perfused capillaries in the cremaster muscle (P<0.01), which did not restore in the first hour post-cpb. One hour post- CPB, renal perfusion (258±173 to 135±88, P=0.03) was reduced, paralleled by increased plasma levels of creatinine (28±3 to 58±13 nmol/ml, P<0.01). Aprotinin preserved cremaster perfusion following CPB (P=0.002), whereas renal perfusion (P>0.9) was not affected compared to untreated animals. In parallel, no differences were observed in plasma levels of creatinine (P>0.9). Aprotinin treated animals required less additional fluids (3.9±3.3 vs 7.5±3.0 ml, P=0.006) during CPB and reduced kidney wet/dry weight ratios (4.6±0.2 vs 4.4±0.2, P=0.046) were found 1 hour post-cpb compared to untreated animals. Conclusion Treatment with aprotinin preserved cremaster microcirculatory perfusion following CPB, but did not prevent renal perfusion disturbances nor renal injury following CPB despite reducing renal edema formation. Abstracts wetenschapsdag

9 Remote ischaemic preconditioning and postoperative myocardial injury in patients undergoing pancreatic surgery: a randomised controlled trial L. van Zeggeren 1, R.A. Visser 1, I.M. Dijkstra 3, M. Bosma 3, H.C. van Santvoort 2, P.G. Noordzij 1 1 Department of Anesthesiology, Intensive Care and Pain medicine 2 Department of Surgery 3 Department of Clinical chemistry St. Antonius Hospital Nieuwegein Myocardial injury after major abdominal surgery is common and associated with adverse outcome. Remote ischaemic preconditioning (RIPC) uses brief periods of nonlethal ischaemia and reperfusion to protect organs from ischaemic insults and has been described to reduce serum cardiac troponin (ctn) release after cardiac surgery. We did a single center, doubleblind randomised controlled trial to establish whether RIPC reduces myocardial injury after pancreatic surgery. 90 adult patients undergoing elective pancreatic surgery were randomly assigned to a RIPC group (n=45) or a control group (n=45) after induction of anesthesia. RIPC consisted of three 5 minute cycles of left upper limb ischaemia, induced by a cuff inflated to 200 mmhg, with an intervening 5 minutes of reperfusion. High sensitive serum ctn-t concentration was measured before the intervention and at 4, 12, 24, and 48 hours after surgery. Primary endpoint was maximum postoperative ctn-t concentration, secondary endpoints were 30 day postoperative complications and length of stay in the intensive care and the hospital. Analysis was by intention to treat. Maximum postoperative ctn-t was 21 ug/ml (± 39) in the RIPC group versus 44 ug/ml (± 133) in the control group (P = 0.28). Postoperative ctn-t release in RIPC and control patients compared to baseline was 1 ug/ml (± 2) vs 2 ug/ml (± 1) at 4 hours (P = 0.50); 8 ug/ ml (± 37) vs 3 ug/ml (± 11) at 12 hours (P = 0.38); 5 ug/ml (± 18) vs 4 ug/ml (± 8) at 24 hours (P = 0.69) and 4 ug/ml (± 12) vs 15 ug/ ml (± 70) at 48 hours (P = 0.37). There was no difference in the incidence of a severe postoperative complication between groups (15 patients (33%) in the RIPC group versus 21 patients (53%) in the control group, P = 0.197), but a trend towards a shorter intensive care length of stay was observed in RIPC patients (1.8 days (± 0.2) versus 2.7 days (± 0.4), P = 0.065). Conclusion Remote ischaemic preconditioning does not reduce postoperative cardiac troponin-t release in patients undergoing elective pancreatic surgery. Abstracts wetenschapsdag

10 Abstracts Perioperative Outcomes Perioperative Outcomes The impact of decreased skeletal muscle mass on short term outcome after abdominal aortic aneurysm repair R.M. Smoor, S. Brouwers, H.P.A. van Dongen, R. Kropman, P.G. Noordzij St. Antonius Ziekenhuis Nieuwegein Perioperative mortality after elective endovascular repair (EVAR) of AAA is lower compared to open surgical repair (OSR), but associated with worse long-term outcomes. Risk stratification is important for the surgical treatment decision, especially in older patients at risk for frailty. Loss of muscle mass is an important aspect of frailty and associated with poor outcome. Measurement of muscle mass may improve risk stratification in AAA surgery patients. The objective of this study is to determine the association of skeletal muscle mass with adverse outcome after AAA surgery. In this historical cohort study the cross sectional muscle mass (CSMA) of patients with elective AAA repair was evaluated on preoperative computed tomography (CT) scans on the third vertebrae level and corrected for height resulting in a muscle index (CSMI). The lowest tertile of the CSMI was used as a cut-off for low muscle mass. Primary outcome was complications (Clavien-Dindo > grade II) including 30-day mortality. The association of CSMI with the primary outcome was assessed using multivariate logistic regression analysis and adjusted for sex and POSSUM physiology score. In total, 791 patients underwent elective AAA repair of which 489 were eligible. Of these, 177 (36.2%) were OSR-, and 312 (63.8%) EVAR patients. In the EVAR group, no association was found. However in the OSR group, CSMI was significantly lower in patients with a poor outcome (47.3 cm2/m2 vs cm2/m2, p-value 0.024). Low muscle mass and poor outcome were significantly associated in univariate analysis (OR % CI , p-value 0.04). Multivariate analysis revealed a decreased risk of poor outcome with higher CSMI (OR % CI , p-value 0.034). Conclusion Patients with decreased CSMI are at greater risk for adverse outcome after open AAA surgery. The preoperative measurement of the CSMA may be an appropriate tool to identify patients with higher operative risk: these patients might benefit from an EVAR. Wireless Vital Signs Monitoring Using Wearable Sensors in Patients at the Step Down Unit and Surgical Ward: a Clinical Validation Study M. Breteler 1,2, E. KleinJan 1,3, T. Blokhuis 4, R. van Hillegersberg 5, J. Ruurda 5, K. van Loon 1, L. Leenen 6, C. Kalkman 1 1 Department of Anesthesiology, University Medical Center Utrecht, Utrecht University 2 Luscii Healthtech BV, Amsterdam 3 Technical Medical Centre, University of Twente, Enschede 4 Department of Surgery, Maastricht University Medical Center 5 Department of Surgery, University Medical Center Utrecht 6 Department of Trauma Surgery, University Medical Center Utrecht Abstracts wetenschapsdag

11 Abstracts Perioperative Outcomes Vital signs are usually recorded once every 8h in patients at the hospital ward. Early signs of patient deterioration may therefore be missed. Wearable and wireless sensors have been developed that may capture patient deterioration at an earlier stage. The objective was to determine whether two wearable sensors, HealthPatch (VitalConnect San Jose, CA), SensiumVitals (Oxford, UK) and a bed-based mattress sensor (EarlySense, Ramat Gan, Israel) can reliably measure heart rate (HR) and respiratory rate (RR) continuously in high-risk surgical patients. Observational methods comparison study, approved by the institutional ethics committee. In consenting high-risk surgical patients HR and RR were simultaneously recorded on the step-down unit and surgical ward with HealthPatch, Sensium- Vitals and EarlySense and are compared with a wireless reference device (Radius-7) containing a pulse oximeter and an acoustic respiration sensor (Masimo, Irvine, CA). Outcome measures were 95% limits of agreement (LoA) and bias (Bland-Altman analysis). A 15 min median filter was applied to remove transients caused by patient movement. Clarke Error Grid Analysis was performed to assess the consequences for clinical decision making. Additionally, the number of adverse events during measurement period were collected and evaluated. During a 9 month period in 2017, 31 high-risk surgical patients (trauma, esophegectomy) entered the study. Over 2800 hours of vital signs data were available for analysis. Gaps with no data > 15 min were observed in 3% of time. Bias and LoA for HR from HealthPatch, SensiumVitals and EarlySense were 1.9 ( ), 1.8 ( ) and -1.1 ( ) beats/min respectively. For RR, bias and LoA of HealthPatch, SensiumVitals and EarlySense were 4.2 ( ), -0.1 ( ) and 0.2 ( ), breaths/min respectively, For HR, adequate treatment decisions would have been taken in 99.4%, 99.2% and 99,8% with Health- Patch, SensiumVitals and EarlySense resp[ectively. For RR, this would have been 78%, 98% and 99% respectively. The various adverse events are presented in Table 1, of which atrial fibrillation occurred most frequently (24%). Masimo-Radius 7, that uses pulse oximetry, and EarlySense, that uses ballistocardiography to derive HR, both underestimate HR in cases of atrial fibrillation with high ventricular rate (Figure 1). Conclusion All tested wearable sensors were highly accurate for HR. For RR, the bed-based EarlySense device was reasonably accurate, but does not provide data during mobilization of the patient. The accuracy for respiratory monitoring of the wearable patch SensiumVitals was reasonably accurate, whereas the other patch sensor (HealthPatch) was outside acceptable limits. Reduced RR accuracy (from talking and moving) and a possibility of false high RR alarms should be taken into account in awake patients. We consider these sensors as promising innovations that may timely detect patient deterioration. Future studies should focus on the trending ability to detect patient deterioration at the general ward, and perhaps even continued monitoring after discharge home yr old male patient after esophagectomy HR (bpm) ICU readmission 50 Mar 08, 00:00 Mar 08, 12:00 Mar 09, 00:00 Mar 09, 12: RR (brpm) ICU readmission Anastomotic leak Atrial Fibrillation Pneumothorax Mar 08, 00:00 Mar 08, 12:00 Mar 09, 00:00 Mar 09, 12: Abstracts wetenschapsdag

12 Early postoperative data: relevance and future perspectives for the Anesthesiologist V.G.B. Liem, S.E. Hoeks, K.H.J.M. Mol, R.J. Stolker, F. van Lier Erasmus Medical Center, Rotterdam Background For anesthesiologist vast amounts of physiological patient data, that can be used for analyses are created during surgery. The value of (early) postoperative data however, is often unknown. This presentation will discuss the importance of postoperative data and its potential within the field of anesthesiology. Exemplary data are derived from a prospective troponin surveillance cohort, from 2012 to 2017 at the Erasmus Medical Center in the Netherlands. Data were retrospectively analyzed. Patients were aged 60 years, underwent moderate to major noncardiac surgery and had frequent postoperative hemodynamic monitoring on a postoperative high-dependency ward for up to 24 hours. Intra- and postoperative hemodynamic parameters were recorded and extracted. The primary study endpoint was myocardial injury within the first postoperative 3 days. Multivariable logistic regression models were used to investigate the association between postoperative hemodynamics and myocardial injury. Postoperative hypotension after surgery was common, e.g. 2 cumulative hours below a threshold of 60 mmhg occurred in 8% of the patients whilst 4 hours below a threshold of 75 mmhg occurred in 48% of the patients. Postoperative tachycardia was similarly common; with 14% of the patients experiencing a heart rate 100 beats per minute (bpm) for at least one hour. After adjusting for potential confounders various cumulative durations of hypotension and tachycardia were associated with myocardial injury. Early postoperative continuous monitoring is warranted and potentially important in predicting patients deterioration in which anesthesiologists may be able to intervene to reduce adverse outcome. Conclusion The usage of (early) postoperative data is a relative unknown aspect for the specialty and might be relevant for improving outcome. Abstracts wetenschapsdag

13 Physicians opinions regarding anticoagulant therapy in patients with a limited life expectancy B.A.A. Huisman 1, 2,, E.C.T. Geijteman 3,4, N. Kolf 4, M.K. Dees 5, L. van Zuylen 3, K.M. Szadek 1, M.A.H. Steegers 1, A. van der Heide 4 1 Department of Anesthesiology, Amsterdam UMC, Vrije Universiteit Amsterdam 2 Hospice Kuria, Amsterdam 3 Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam 4 Department of Public Health, Erasmus University Medical Center, Rotterdam 5 Department of Primary and Community Care, Radboud University Medical Center, Nijmegen Patients with a limited life expectancy have an increased risk for thromboembolic and bleeding complications. Many of these patients who use anticoagulants have no rationale for this. The aim of this study was to identify the opinions of physicians about the use of anticoagulants in the last phase of life. A mixed method research design was used. A secondary analysis was performed of a questionnaire study and an interview study aimed to understand medication management in the last phase of life. The questionnaire study comprised a vignette of a patient with a limited life expectancy, due to cancer, who used acenocoumarol for the treatment of atrial fibrillation. 174 general practitioners and 147 clinical specialists completed the questionnaire, 8 general practitioners and 15 clinical specialists were interviewed. Physicians would continue or stop an anticoagulant because of the risk for respectively thromboembolic or bleeding complications. The improvement and/ or preservation of the patient s quality of life were a reason for both stopping and continuing an anticoagulant. Other factors the physicians considered in the decision-making were the type of anticoagulant, the indication of the anticoagulant, underlying diseases and the condition and life expectancy of the patient. Factors that made the decision-making difficult were lack of evidence, patient s uncertain life expectancy and the fear of conducting a bad policy. Which decision was eventually made was dependent on the choice of the patient. Conclusion There is a great variation in the physicians opinions regarding the use of anticoagulants in patients with a limited life expectancy. However, the primary goal of each decision is the improvement and/ or maintenance of the patient s quality of life. An important limitation in decision-making is the lack of evidence about the risks and benefits of stopping anticoagulants. Abstracts wetenschapsdag

14 Abstracts Clinical & Experimental Circulation (2) Clinical & Experimental Circulation (2) Association between postoperative myocardial injury phenotypes and disability-free-survival in patients undergoing non-cardiac surgery L.M. Vernooij 12, J.A. van Waes 1, M. McKenny 3, M. Machina 3, S. Feng 3, D.N. Wijeysundera 3, H.M. Nathoe 4, L.M. Peelen 12, W.A. van Klei 1, W. Scott Beattie 3 1 Department of Anesthesiology, University Medical Center Utrecht 2 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht 3 Department of Anesthesia, Toronto General Hospital, Toronto, Canada 4 Department of Cardiology, University Medical Center Utrecht Postoperative myocardial injury (PMI), defined as troponin elevation, has been associated with postoperative morbidity and mortality1 3. PMI may be caused by perioperative myocardial ischemia and infarction. However, PMI has also been related to cardiovascular events including heart failure and arrhythmias, and to non-cardiac complications, such as pulmonary embolism, sepsis and respiratoryand renal failure4,5. The patient centered impact of these associated non-cardiac adverse events has not been compared to PMI. Therefore, we examined the independent prognostic effects of PMI phenotypes and non-cardiac adversity on death and disability following noncardiac surgery. This two-center ongoing prospective cohort study included 325 patients ( 50 years) undergoing elective major non-cardiac surgery under general or spinal anesthesia with an expected hospital stay of 24 hours. All patients signed informed consent. Troponin was measured on the first three postoperative days. Patients were divided into groups based on PMI (using troponin clinical cut-off values as used in the respective hospitals) and the occurrence of postoperative adverse events. This resulted in five groups, i.e. no adverse events (1), isolated PMI (2), cardiac events (3) and non-cardiac events with (4) or without (5) PMI (Figure 1). Patients who experienced no adverse events (cardiac nor noncardiac) served as the reference population. The primary outcome was death or disability within 6 months of surgery. Severe disability was defined as a WHODAS 2.0 >50%, and moderate disability as 25%-50% increase from the preoperative score6. Patients who died were classified as being fully disabled (WHODAS 2.0 score of 100%). Multivariable logistic regression was used to investigate the association between PMI subtypes and disability free survival. This study was approved by the local institutional ethics boards in both centers and was registered at clinicaltrial.gov (NCT ). In total, we included 372 patients, of whom 325 provided complete information on follow-up. Troponin was elevated in 65 patients (20%) (Figure 1). Cardiac events occurred in 25 patients (7%). Baseline characteristics are presented in Table 1. At 6 months, 17 patients (6%) were severely disabled and 16 (5%) patients had died (Figure 1). Disability free survival was similar in patients with and without PMI (OR: 1.2 (95% CI , p=0.112). Non-cardiac events without PMI were associated with death and disability (OR: 3.4 (95% CI , p=0.04). No association was demonstrated for the other PMI phenotypes, i.e. isolated PMI (OR: 1.0 (95% CI , p=0.95), cardiac events (OR: 1.4 (95% CI , p=0.46) and non-cardiac events with PMI (OR: 1.8 (95% CI , p=0.47). Conclusion In our study, non-cardiac adversity events were found to increase death and disability. Conversely, the effect size for association between cardiac events, isolated PMI and disability were small and not statistically significant. This is an ongoing study in which additional patients are included which allows us to better estimate the investigated association. Abstracts wetenschapsdag

15 Abstracts Clinical & Experimental Circulation (2) References 1. Circulation. 2013;127(23): Can J Anaesth. 2012;59(11): JAMA. 2017;317(16): Anesth Analg. 2016;123(1): Anesth Analg. 2018;127(5): , 6. Anesthesiology. 2015;122(3): van Waes JAR, Nathoe HM, de Graaff JC, et al. Myocardial injury after noncardiac surgery and its association with short-term mortality. Circulation. 2013;127(23): doi: /circulationa- HA Beattie WS, Karkouti K, Tait G, et al. Use of clinically based troponin underestimates the cardiac injury in non-cardiac surgery: a single-centre cohort study in 51,701 consecutive patients. Can J Anaesth. 2012;59(11): doi: / s van Waes JAR, Grobben RB, Nathoe HM, et al. One-Year Mortality, Causes of Death, and Cardiac Interventions in Patients with Postoperative Myocardial Injury. Anesth Analg. 2016;123(1): doi: / ANE Beattie WS, Wijeysundera DN, Chan MT V., et al. Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival. Anesth Analg. 2018;127(5): doi: / ANE Shulman MA, Myles PS, Chan MT V, Mc- Ilroy DR, Wallace S, Ponsford J. Measurement of disability-free survival after surgery. Anesthesiology. 2015;122(3): doi: /aln Devereaux PJ, Biccard BM, Sigamani A, et al. Association of Postoperative High- Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery. JAMA. 2017;317(16):1642. doi: / jama Abstracts wetenschapsdag

16 Non-invasive oscillometric versus invasive arterial blood pressure measurements in critically ill patients T. Kaufmann 1, E.G.M. Cox 2, R. Wiersema 2, B. Hiemstra 1, T.W.L. Scheeren 1, B. Saugel 3,4, I.C.C. van der Horst 2,5 1 Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen 2 Department of Intensive Care, University Medical Center Groningen, University of Groningen, Groningen 3 Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 4 Outcomes Research Consortium, Cleveland, Ohio, USA 5 Department of Intensive Care, Maastricht University Medical Center, University of Maastricht An invasive measurement by an arterial line is the reference method for blood pressure monitoring in critically ill patients. Blood pressure monitoring can also be performed non-invasively by intermittent oscillometric measurement but may exhibit limited measurement performance, especially in hemodynamically unstable patients. We aimed to compare blood pressure measurements obtained using upper-arm cuff oscillometry with arterial catheterderived blood pressure measurements in critically ill patients. This study was a post hoc analysis of the SICS-I study (1). Non-invasive blood pressure was measured once within 24 hours of ICU admission via automated brachial cuff oscillometry and simultaneously the arterial catheter-derived measurement was recorded. Measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were compared by Bland-Altman and error grid analyses (2). Of 1075 SICS-I patients, 736 patients (68%) had a pair of invasive and non-invasive blood pressure measurements. The observed mean difference (±SD, 95% limits of agreement) between oscillometrically and invasively measured blood pressure was 0.8 mmhg (±15.7 mmhg, mmhg) for SAP, -2.9 mmhg (±11.0 mmhg, mmhg) for DAP, and -1.0 mmhg (±10.2 mmhg, mmhg) for MAP (Figure 1). Error grid analysis showed that the proportions of measurements in risk zones A-E were 82.3%, 13.2%, 4.2%, 0.3%, and 0% for SAP and 78.3%, 20.7%, 0.1%, 0%, and 0.01% for MAP, respectively (Figure 2). Conclusion Non-invasive blood pressure measurements using upper-arm cuff oscillometry showed poor statistical agreement compared to direct invasive measurements in critically ill patients. Non-invasive blood pressure measurements are clinically unacceptable as an alternative for invasive arterial blood pressure measurements in critically ill patients. References Hiemstra et al. Intensive Care Med. 2019;45(2): Saugel et al. Anesth Analg. 2018;126(4): Figure 1 Figure 2 Abstracts wetenschapsdag

17 Figure 3 Use of a machine-learning algorithm in combination with treatment guidance reduces hypotension during surgery: a randomized clinical trial M. Wijnberge 1,2, B.F. Geerts 1, L. Hol 1, N. Lemmers 1, M.P. Mulder 1,3, P. Berge 1, J. Schenk 1, L.E. Terwindt 1,M.W. Hollmann 1, A.P. Vlaar 2, D.P. Veelo 1 1 Amsterdam UMC, location AMC, Department of Anesthesiology, Amsterdam 2 Amsterdam UMC, location AMC, Department of Intensive Care, Amsterdam 3 University of Twente, Department of Technical Medicine, Enschede Intraoperative hypotension occurs often, is associated with adverse postoperative outcomes and current treatment is reactive. The development of a machine learning (ML) predictive algorithm opens up possibilities to prevent hypotension. We hypothesized that the use of this predictive algorithm in combination with treatment guidance would reduce the time weighted average (TWA) of intraoperative hypotension. This was a two-phased trial. Phase A: A prospective cohort study in 40 patients. Phase B: A randomized clinical trial in 60 patients. Adult patients scheduled for elective noncardiac surgery under general anesthesia and an indication for an arterial line were included. Our primary outcome was TWA in hypotension during surgery. Hypotension was defined as a MAP below 65 mmhg. Our secondary outcomes included TWA in hypertension (MAP > 100 mmhg) and the cumulative dose of medication given during surgery. The TWA in hypotension was 0.44 [IQR ] in the control group versus 0.10 [ ] mmhg in the intervention group, median difference mmhg, (95% CI to -0.14), p= There was no difference in TWA in hypertension and neither the cumulative dose of vasoactive medication given nor the fluid balance was significantly higher in the intervention group. Conclusion Use of this ML-algorithm in combination with treatment guidance resulted in a reduction in hypotension without an increase in hypertension or in the cumulative dose of medication used. These results are promising and open up the field for studies assessing clinical endpoints such as organ injury, mortality and cost-effectiveness. Abstracts wetenschapsdag

18 Abstracts Pain & Palliative Care (1) Pain & Palliative Care (1) Magneto-encephalography to image the effects of chronic pain and Spinal Cord Stimulation Bart Witjes 1,2, Mathieu Roy 3, Elizabeth Bock 2, Robert Oostenveld 4, Frank Huygen 1, Sylvain Baillet 2, Cecile de Vos 1,2 1 Center for Pain Medicine, Erasmus Medical Center, Rotterdam, the Netherlands 2 Montreal Neurological Institute, McGill University, Montreal, Canada 3 Department of Psychology, McGill University, Montreal, Canada 4 Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands Biomarkers are key for personalized interventions in Medicine and could be used to optimise, predict and monitor treatment success. For chronic pain such markers are still very limited available (e.g. Biomarkers in Rheumatoid Arthritis). Markers derived from functional brain imaging, could be an adequate approach for this aim and could help to better understand the pathophysiology of chronic pain. It potentially also could help to monitor the effect and the working mechanisms of interventions like Spinal Cord Stimulation (SCS). We aim to develop a marker sensitive and specific enough to assess objectively, each individual pain patient s condition. We used magnetoencephalography (MEG), a tool for functional brain imaging, and derived signal measures previously reported: slowing in alpha frequency brain oscillations during rest. Resting-state MEG was recorded in pain-free control subjects, chronic pain patients, and in patients evaluating tonic, burst and placebo SCS. The power spectrum density was calculated at each of the 275 MEG-sensors. By calculating the ratio of low-alpha to high-alpha power, we assessed the amount of slowing of the dominant brain rhythm. This study is still in progress. So far, 25 controls, 27 chronic pain patients and 9 patients with SCS have been included. Majority of the chronic pain patients showed slowing of the alpha activity over parietal, occipital and lateral brain regions as compared with controls. Patients with SCS showed on average more slowing of brain activity with placebo stimulation than with tonic or burst stimulation. Conclusions Our preliminary findings suggest that alpha frequency brain oscillations are slowed down in chronic pain patients and that both tonic and burst SCS can reduce this slowing. Alternatives to the classical opioid analgesics characterized by utility functions to determine toxicity versus safety H. Algera, E. Olofsen, M. van Velzen, M. Niesters, L. Aarts, A. Dahan Department of Anesthesiology, Leiden University Medical Center The current world-wide opioid epidemic warrants the development of alternatives to current opioid analgesics, most importantly to oxycodone. Current opioids are overprescribed and consequently lead to misuse, abuse, addiction Abstracts wetenschapsdag

19 Abstracts Pain & Palliative Care (1) and lethal toxicity. This is especially true in the United States where the number of opioids death is soaring. Opioid-lethality is due to cardiorespiratory collapse secondary to hypoxia and opioid-induced respiratory depression. Consequently, new opioid analgesics are being developed and older opioids are being reintroduced that might possess less respiratory toxicity. We developed highly sensitive experimental functions that allow the characterization of opioid toxicity in light of its analgesic efficacy and calculated the utility of several bi- and multifunctional opioids and one biased ligand in human volunteers. We tested the following novel opioids: R-dihydroetorphine (RDHE), an opioid agonist at MOP, KOP and DOP receptors; tapentadol, a MOP receptor agonist and noradrenaline re-uptake inhibitor; oliceridine, a G-protein selective MOP agonist; and the following classical opioids (controls): morphine, fentanyl and oxycodone. We measured the effect of these opioids on two end-points, antinociception and respiratory depression, in healthy young volunteers. Respiration was measured at isohypercapnia, using the dynamic end-tidal forcing technique, antinociception was measured using the following assay: electrical pain (RDHE), pressure pain (tapentadol) or the cold pressor test (oliceridine). After pharmacokinetic-pharmacodynamic analyses the utility function (UF) was calculated as follows: UF1 = P(A) P(R) and UF2 = P(A AND NOT R), where P(A) is the probability for analgesia and P(R) the probability for respiratory depression. Over the clinical concentration range, negative utilities (UF1) were observed for the control opioids, indicative that morphine, fentanyl and oxycodone have a higher probability of respiratory depression than analgesia. Over the clinical concentration range, the UF1 of the three novel opioids ranged from neutral (P(A) = P(R)) for tapentadol to positive (P(A) > P(R)) for oliceridine. Similarly, the second utility, UF2, was more in favor of the novel opioids than the controls. The most promising new opioid was oliceridine that had a twofold lesser potency than morphine in producing respiratory depression at doses where the two opioids were equianalgesic. Conclusions We contend with care that, although performed in volunteers using surrogate end-points of analgesia and respiratory depression, these studies may well be translated into clinical practice and consequently we conclude that compared to the prototypical opioids, these bifunctional opioids and especially the G-protein selective MOP agonist oliceridine has a favorable safety profile when considering both analgesia and respiratory depression. Genome-wide association analysis identifies potential risk loci for chronic postsurgical pain R.I. van Reij 1,2, D.M.N. Hoofwijk 1, B.P.F. Rutten 2,3, G. Kenis 2,3, M. Theunissen 1, L. Weinhold 6, M. Leber 5, M. Knapp 6, S. Heilmann-Heimbach 7, M.M. Nöthen 7, P. Hoffman 7, M. Schmid 6, M. Allegri 8, G. Cappelleri 8, M. De Gregori 8, W.F.F.A. Buhre 1, E.A.J. Joosten 1,2, A. Ramirez 4,5, N.J. van den Hoogen 1,2 1 Dept. of Anesthesiology and Pain Management, Maastricht University Medical Center +, Maastricht, The Netherlands 2 School for Mental Health and Neuroscience (MHeNs), Maastricht univ., Maastricht, The Netherlands 3 Dept. of Psychiatry and Neuropsychology, Maastricht univ., Maastricht, The Netherlands 4 Dept. of Psychiatry and Psychotherapy, Univ. of Bonn, Bonn, Germany. 5 Dept. of Psychiatry and Psychotherapy, Univ. of Cologne, Cologne, Germany 6 Dept. of Medical Biometry, Informatics and Epidemiology, Univ. Hospital Bonn, Bonn, Germany 7 Institute of Human Genetics, Univ. of Bonn, Bonn, Germany 8 Italian Pain Group, Parma, Italy Abstracts wetenschapsdag

20 Chronic Post-Surgical Pain (CPSP) affects between 5-85% of patients undergoing surgery, with a large negative impact on the quality of life. Research into the genetic risk factors of CPSP provided contradictory results and a lack of consensus. The primary objective of this study was the identification of genetic risk factors for the development of CPSP 3 months after surgery using a genome-wide approach. The protocol for this study was reviewed and approved by the local Medical Ethical Committees. Protocols of the studies have been registered under the following numbers: NTR2702, NCT ,NCT A prospective discovery cohort of women (n=330) undergoing hysterectomy and a replication cohort of women (n = 87) undergoing surgery for various indications were analysed in a Genome-Wide Association Study (GWAS). Peripheral blood samples were collected and genotyped using the Illumina PsychArray. Genotype imputation was performed using Minimac3 with a European reference panel. The statistical analysis compared patients who developed severe CPSP (NRS>3) with those who developed no CPSP(NRS=0). SNPs were analysed using an additive logistic regression. Genome-wide significance was set at P<5x10-8. SNPs with a P-value<1x10-5 were selected as SNPs of interest for targeted analysis in the replication cohort and for the meta-analysis. A polygenic risk score (PRS) analysis was conducted on systematically selected GWAS studies in chronic pain, headaches and migraine. The PRS was calculated using the PRSice software Out of the 330 patients in the discovery sample, 10% developed severe CPSP (NRS>3) and 81% had no CPSP (NRS = 0) at three months after the surgery. Out of the 87 patients in the replication sample, 11,5% developed severe CPSP and 46% had no CPSP at three months after the surgery. Although no SNP reached genomewide significance in the discovery cohort, several SNPs showed association with CPSP at P<1x10-5. Meta-analysis showed a significant association with CPSP for the loci CRTC3 and IQGAP1. PRS analysis showed a significant difference between the severe chronic pain and no chronic pain group based on the results of a study on sciatica (Lemmelä et al., PLoS One. 2016) indicating a possible common genetic background between the different chronic pain phenotypes. No significant results were found in PRS based on headache or migraine research. Conclusions Various SNPs of interest were identified and analysed further in the replication study. The meta-analysis identified two loci potentially associated with CPSP (CRTC3 and IQGAP1). PRS analysis showed a possible common background between CPSP and peripheral pain syndromes. The present study provides an important first step in elucidating the genetic risk factors of CPSP. Future work will validate these results in larger independent cohorts which will be done in collaboration with Radboud UMC. Funds made available by Dept. of Anaesthesiology (Maastricht University Medical Center + ), School of Mental Health and Neuroscience (Maastricht University) and Italian Health Ministry (GR ) Abstracts wetenschapsdag

21 Abstracts Pulmonary Physiology/Gas Exchange Pulmonary Physiology/Gas Exchange Positive end-expiratory pressure affects the position and function of the human diaphragm D. Jansen 1, A.H. Jonkman 2, H.J. de Vries 2, C. Keijzer 1, A.R.J. Girbes 2, T. Marcus 3, C.A.C. Ottenheijm 4, L.M.A. Heunks 2 1 Department of Anesthesiology, Radboud University Medical Center, Nijmegen 2 Department of Intensive Care Medicine, 3 Department of Radiology, 4 Department of Physiology, Amsterdam UMC, location VUmc Amsterdam Mechanical ventilation with positive end-expiratory pressure (PEEP) helps to prevent airway collapse and thereby improves oxygenation. However, the effects of PEEP on the diaphragm itself are largely unknown. Experimentally, we demonstrated that PEEP shortens the diaphragm muscle fibers. 1 It is hypothesized that this might lead to a decreased diaphragm contractility, since it no longer operates on its optimum length on the force-length relation. Our aim is to investigate the acute effects of PEEP on the position and function of the human diaphragm. Eighteen healthy subjects were instrumented with two nasogastric catheters to measure the electrical activity of the diaphragm (EAdi) and transdiaphragmatic pressures (Pdi) while under non-invasive ventilation (NIV) with PEEP. During the protocol each subject was exposed to four PEEP levels: cmH 2 O. At each level, an end expiratory hold was per- formed to measure the neuromuscular efficiency index (NME). Afterwards, a MRI was performed to determine changes in position, shape and length of the diaphragm at the different PEEP levels. Figure 1 shows a representative example of a static high resolution MRI image of the diaphragm. A gradual caudal displacement of the diaphragm was found with a mean ± SD displacement of 19.8 ± 9.7 mm after increasing the PEEP level from 2 to 15 cmh 2 O. This leads to a decrease in total diaphragm length, up to 55%, and a decrease in the neuromechanical efficiency of the diaphragm, up to 40% (figure 2, left and right, respectively) (p<0.05). Conclusion In healthy subjects, acute application of PEEP results in a caudal diaphragm displacement, shortening of the diaphragm length and a reduction in diaphragm contractile efficiency. If similar effects also occur in the critically ill patient, an acute reduction in PEEP (i.e. during a spontaneous breathing trial) may result in an overstretched diaphragm and consequently impair diaphragm performance. References 1. Lindqvist J. et al. AJRCCM Vol 198, Iss 4, pp , Figure 1. Two high-resolution MR images (sagittal right plane) of a representative subject, during an end-expiratory hold. In green the caudal displacement of the diaphragm due to an increased PEEP level, measured at the top of the diaphragm dome. In yellow the measurement of the length of the anterior and posterior zone of apposition, and diaphragm dome. Abstracts wetenschapsdag

22 Figure 2. Left: PEEP-induced shortening of the total diaphragm length, relative to a PEEP level of 2cmH 2 O. Data are presented in a Tukey boxplot, *P Right: PEEP-induced decrease in neuromechanical efficiency (NME) of the diaphragm. Data represent mixed model estimates of the mean with 95% confidence interval, *P Influence of reversal of a partial neuromuscular block on the ventilatory response to hypoxia: a randomized controlled trial in healthy volunteers M. Boon, S.J.L. Broens, Ch.H. Martini, M. Niesters, M. van Velzen, L.P.H.J. Aarts, A. Dahan Department of Anesthesiology, Leiden University Medical Center The ventilatory response to hypoxia is a life-saving chemoreflex originating at the carotid bodies that is impaired by non-depolarizing neuromuscular blocking agents. We studied the effect of three strategies for reversal of a partial neuromuscular block on ventilatory control in 34 healthy male volunteers on the chemoreflex. We hypothesize that the hypoxic ventilatory response is fully restored following the return to a train-of-four-ratio of 1. In this single center, experimental, randomized, controlled trial, ventilatory responses to 5-min hypoxia (oxygen saturation 80 ± 2%) and ventilation at hyperoxic isohypercapnia (end-tidal carbon dioxide concentration 55 mmhg) were obtained at baseline, during rocuronium-induced partial neuromuscular block (train-of-four-ratio 0.7 measured at the adductor pollicis muscle by electromyography) and following reversal until the train-of-four-ratio reached unity with placebo (n = 12), 1 mg neostigmine/0.5 mg atropine (n = 11) or 2 mg/kg sugammadex (n = 11). We confirmed that low-dose rocuronium reduced the ventilatory response to hypoxia from 0.55 ± 0.22 (baseline) to 0.31 ± 0.21 L. min -1.% -1 (train-of-four-ratio 0.7, p < 0.001). Following full reversal as measured at the thumb, there was persistent residual blunting of the hypoxic ventilatory response (0.45 ± 0.16 L.min -1.% -1, train-of-fourratio 1.0, p < 0.001). Treatment effect was not significant (ancova p = 0.299) with chemoreflex impairment in 5 (45%) subjects following sugammadex reversal, seven subjects (64%) following neostigmine reversal and in 10 subjects (83%) after spontaneous reversal to a train-of-four-ratio of 1. Conclusion Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at TOF ratios greater than 0.9 following reversal with neostigmine and sugammadex or spontaneous recovery of the neuromuscular block. Support: This study is supported by MSD Nederland. Abstracts wetenschapsdag

23 Abstracts Central Nervous System Central Nervous System The Influence of Blood Pressure on Cerebral Autoregulation Efficacy during Propofol and Sevoflurane Anaesthesia R.E.C. van den Dool, R.V. Immink, J. Hermanides, M.W. Hollmann and N.H. Sperna Weiland Department of Anaesthesiology, Amsterdam UMC, location AMC Cerebral autoregulation (CA) is defined as a collection of different quickly and slowly acting mechanisms that regulate cerebral vascular resistance during fluctuations in systemic blood pressure (BP). Static CA (sca) describes the relationship between steady-state mean arterial BP and cerebral blood flow (CBF) and its efficacy is considered to be perfect when CBF is unaffected by different BP levels. Dynamic CA (dca) describes how quickly regulatory mechanisms regulate a sudden change in BP. During propofol anaesthesia, cerebral metabolic rate (CMR) and CBF are reduced while sca remains preserved. During sevoflurane anaesthesia on the other hand CBF does not change while CMR declines and sca is impaired dose dependently. To date, dca efficacy has never been quantified at different levels of BP when subjects are anaesthetised. We set out to determine changes in CBF and CA during a stepwise increase in mean BP in anaesthetised patients. We hypothesized that dca parallels sca. After sample size calculation fifty patients (48±17years, 177±9cm, 87±20kg), 32 males, ASA 1 or 2, without a cardiovascular history, scheduled for non-vascular elective surgery, were included (25 received propofol [6±1mg kg -1 h -1 ] and 25 received sevoflurane [2.0±0.5%]). Continuous finger BP (Nexfin), MCAV (transcranial Doppler ultrasonography) and the end-tidal partial CO 2 pressure were stored with a sample rate of 100 Hz during 10 mmhg stepwise increases in BP elicited by phenylephrine administration. Static CA was quantified by averaging a 2-minute MCAV mean measurement during all different BP levels. Dynamic CA was quantified using frequency domain analysis on 0.1 Hz oscillations in BP and MCAV induced by adjusting the ventilation frequency to 6 cycles per minute. At a mean BP of 60 mmhg MCAV mean during propofol and during sevoflurane were similar (37±15 cm s -1 and 44±12 cm s -1 ; p=ns). We confirmed that static CA is better preserved during propofol compared to during sevoflurane (r=0.17 (95% CI, ) vs (95% CI, ); p<0.05). Stepwise increases in BP improved dynamic CA during propofol but not when sevoflurane was used. (table 1) Conclusion Static and dynamic CA do not parallel. Propofol and sevoflurane anaesthesia influence CBF regulation differently. During propofol, when the brain has to deal with a decreased CMR and CBF, static CA seems intact but the fast-acting regulatory mechanisms are quicker to compensate immediate fluctuations in BP. Sevoflurane induces a state of luxury perfusion (maintained CBF combined with a decreased CMR). Then, static CA seems impaired while dynamic CA is not influenced during changes in BP. Abstracts wetenschapsdag

24 Abstracts Central Nervous System Static and dynamic cerebral autoregulation during sevoflurane and propofol Static Cerebral autoregulation (CA), expressed as 2 minute averaged Middle cerebral artery blood velocity (MCAV), and dynamic CA, expressed as the MCAV mean to mean BP phase lead (dynamic CA) at different levels of blood pressure (BP) during sevoflurane (n=25) and propofol (n=25) anesthesia. Mean±SD.

25 Assessing CO2 toxicity in rat and man: a translational study identifying the effects of high levels of inspired CO2 on cardiorespiratory physiology R. van der Schrier, E. Olofsen, M. van Velzen, M. Niesters, L. Aarts, A. Dahan Department of Anesthesiology, Leiden University Medical Center Carbon dioxide (CO 2 ) is a product of the aerobic metabolism of energy containing nutrients (carbohydrates) in humans and animals and from industrial combustion processes. Due to the rise in global carbon dioxide exhaust there is the need for carbon dioxide capture and storage. CO 2 is captured in industrial plants and transported via pipelines to underground storage facilities. Transport and storage are performed under relatively high pressure to deal with the large quantities of CO 2 that are being produced worldwide. In case of accidents (e.g. pipeline failures and/or problems at storage facilities) the rapid release of large quantities of carbon dioxide may occur into the atmosphere resulting in elevated inhaled carbon dioxide concentrations by humans (workers and/or bystanders/ inhabitants). High levels of inhaled CO 2 can be extremely hazardous for human health. CO 2 exerts its toxicity through two different mechanisms. Most important is the displacement of oxygen (carbon dioxide is heavier than air) causing a hypoxic environment and toxicity from asphyxia. Second, carbon dioxide itself is harmful due to sympathico-excitation and acidosis. To better understand carbon dioxide toxicity, we tested the physiological effects of inhaled carbon dioxide in human volunteers (max. inhaled conc. 12%) and rats (max. inhaled conc. 50%). Young human volunteers we tested at 8, 10 and 12 kpa (» vol.%) CO 2 with each concentration inhaled for 10, 30 and 60 min. All subjects had an arterial line for gas analysis and cardiac output measurement. Strict stopping rules were applied based on behavior, cognition, arterial ph, heart rate and blood pressure. In rats, we tested five CO 2 concentration (10, 20, 30, 40 and 50%; n = 6 in each group) on behavior, ph, mortality and post mortem tissue damage. In humans carbon dioxide inhalation < 10 min is feasible up to a concentration of 12% without causing loss of consciousness or convulsions. Impairment of cognition, increased levels of anxiety, respiratory acidosis, increased brain oxygenation, and sympathetic excitation occur in a dose-dependent fashion. In rats we observed narcosis and irreversible tissue damage (lung hemorrhage, edema, emphysema) at inhaled CO 2 levels > 30% with the concentration causing death (LC 50 ) in between 40 and 50% at ph of 6.5 ± 0.02, po ± 2.0 kpa and [Glucose] 19 ± 4 mm. Conclusion In humans, short exposures (10 min or less) to high levels of CO 2 (max. 12%) are without consequences in this population of young and healthy volunteers. Extrapolation of the animal data for ph was feasible and suggests that after 10 min of 50% carbon dioxide inhalation ph reached 6.58 in humans. Mortality is difficult to predict in humans and depends on the complex interaction of low ph, hypoxia and pulmonary damage. In a reallive population we expect that at lower carbon dioxide levels critical damage to tissues (e.g. heart failure, vascular damage in the brain, pulmonary edema) might occur, especially in individuals that are sensitive to cardiovascular damage and those with poor resilience. Support: This study was supported by Royal Dutch Shell, The Hague. Abstracts wetenschapsdag

26 Abstracts Central Nervous System The BRAIN-PROTECT study on prehospital treatment of severe TBI: Study design and first results S.M. Bossers (on behalf of the BRAIN-PROTECT collaborators) Amsterdam UMC, location VUmc Amsterdam Severe traumatic brain injury (TBI) is associated with high mortality and morbidity. Early effective treatment is indispensable and starts in the prehospital phase. However, evidence for most prehospital treatment strategies is lacking. The BRAIN-PROTECT study aims to identify prehospital treatment strategies associated with beneficial outcomes. BRAIN-PROTECT is a prospective, observational study. Patients with head trauma and a Glasgow Coma Scale (GCS) score 8 were included. Patients were identified by all helicopter emergency medical services (P-HEMS) in the Netherlands and prospectively followed in 9 participating trauma centres (Figure 1). Prehospital data (e.g. operational data, demographics, trauma mechanism, vital parameters, prehospital interventions and medication) as well as inhospital and outcome data (e.g. mortality, length of stay, functional outcome) were recorded. Substrata on confirmed TBI and isolated TBI were constructed patients were prospectively enrolled in the study (February December 2017). 81.8% were primarily transferred to a participating trauma center. Age ranged between 1-97 years (mean 45.5±23.2) and 70.8% was male (Figure 2). Traffic related trauma (57.5%), particularly bicycle related (21.5%), was the most dominant type of injury, followed by high energy fall (29.1%). The median first GCS was 4 (IQR 3-6). There were 1613 confirmed TBI patients and 811 patients with isolated TBI. The mean proportion of 30-day mortality for all patients was 0.39 (95%CI ), for confirmed TBI 0.42 (95%CI ) and for isolated TBI 0.41 (95%CI ). Conclusion The most optimal prehospital treatment of severe TBI is unknown. The epidemiologic data of the BRAIN-PROTECT study highlight common causes of TBI in the Netherlands and demonstrate high mortality. The BRAIN-PROTECT data will further be used to identify optimal treatment strategies for patients with suspected severe TBI in the prehospital setting. Fig. 1: Legend fig. 1: Participating HEMS & trauma centers Abstracts wetenschapsdag

27 Fig. 2: Female Male Age (years) All patients Age (years) Confirmed 15 TBI Percentage (%) 15 Age (years) Isolated 15 TBI % 10% 5% 0% 5% 10% 15% The Anaesthetic Biobank of Cerebrospinal Fluid - methods and baseline results C. Tigchelaar, S.D. Atmosoerodjo, R. Absalom Department of Anaesthesiology, University Medical Center Groningen, University of Groningen Our Anaesthetic Biobank of Cerebrospinal Fluid (ABC) collects CSF from patients undergoing spinal anaesthesia. This facilitates the study of CSF biochemistry in a relatively healthy surgical popula- tion and the estimation of reference values for new biomarkers. We present the initial technical and laboratory findings. Patients 18 years scheduled for elective surgery under spinal anaesthesia are included. A Montreal Cognitive Assessment (MoCA) and neurological examination are performed preoperatively. 20 ml blood is collected during IV cannulation and 10 ml of CSF is aspirated prior to intrathecal local anaesthetic injection. Sensory block height is measured 10 minutes after spinal injection. Relevant clinical, surgical and anaesthetic data are registered. For comparison of block height, data from a retrospective control group (106 Abstracts wetenschapsdag

28 patients) was collected. 10 ml blood and 2 ml CSF are sent for routine laboratory analyses. The remaining material is centrifuged and stored at -80 C. Qalb (CSF/plasma albumin concentration) is calculated to assess blood-brain barrier (BBB) function. 275 patients (age years, BMI kg/m 2 ) were enrolled between October 2016 and November 2018 (Table 1). The range of MoCA scores was (median 27). CSF was obtained in 254 patients. Mean CSF volume aspirated was 9.1 ml. The median block height was T8 (IQR T6 T10) and was similar to that in the control group (T7, IQR T5 T9) (p=0.423). Block height is associated with type, baricity and dose of local anaesthetic agent (Figure 1 and 2), and CSF biochemistry (data not shown here). Qalb correlates strongly with age, BMI, gender and ASA (each p<0.001) (Figure 3). Conclusion CSF aspiration does not alter block height. Analyses of monoamine neurotransmitters, kynurenines, steroids and a novel biomarker are underway. We are open to suggestions for collaborations with other interested groups. Sensory block height (dermatome) C6 C7 C8 T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 L1 L2 L3 L4 Control Group Frequency 10 ABC Frequency Figure 1. Sensory block height for the ABC (n=255) and control (n=106) group 60 C6 C7 C8 T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 L1 L2 L3 L4 Figure 2. Influence of choice of local anaesthetic agent on sensory block height. In the ABC group, type of local anaesthetic used had a significant effect on the extent of block (p<0.001). For all three local anaesthetic agents, block height was not significantly different between the ABC and control group. 20 ASA score I II III 15 Qalb * 10^ Age (years) Table 1. Patient and spinal anaesthesia characteristics. Continuous data are presented as mean ± standard deviation or median [inter quartile range] as indicated. Discrete data expressed in frequencies (percentage). Figure 3. Correlation between age and Qalb (p<0.001), subdivided for ASA score Abstracts wetenschapsdag

29 Abstracts Perioperative Medicine Perioperative Medicine Emergency front- of- neck- airway (efona). Perspectives on preparedness, training and clinical practice L.A. Bruijstens, on behalf of all co-authors for individual studies 1 Unpublished data, authors: L.A. Bruijstens 1, C.R.M.G. Fluit 1, G.J. Scheffer GJ 1, F.J.A. van den Hoogen 1 and M.A.H. Steegers 2. 1 Radboudumc Nijmegen 2 Amsterdam UMC 2 Unpublished data, abstract submitted, authors: L.A. Bruijstens 1, M. Vorstenbosch 1, C.P. Bleeker 1, J. Honings 1, F.J.A van den Hoogen 1 and M.S. Kristensen 2. 1 Radboudumc, Nijmegen 2 Rigshospitalet, Copenhagen, Denmark 3 Unpublished data, abstract submitted, authors: L.A. Bruijstens 1, T. Loonen 1, G.J. Scheffer 1 and T. Maal 1. 1 Radboudumc Nijmegen 4 Unpublished data, abstract submitted, authors: L.A. Bruijstens 1, D. Jansen 1, J. Bruhn 1, G.J. Scheffer 1, W.H. Teoh 2 and M.S. Kristensen 3. 1 Radboudumc Nijmegen 2 Private Anaesthesia Practice, Singapore 3 Rigshospitalet, Copenhagen, Denmark The low incidence, high stakes character of efona procedures, makes traditional quantitative clinical research challenging. Preparedness, technique of choice, training design and content and model to train on remain topics for debate. In the absence of high level of evidence, a project was initiated in Nijmegen in 2013 with the aim of obtaining and sharing experiences and evidence in above mentioned topics. An educational program in efona procedural skills was developed by an interdisciplinary team. Participants were structurally trained in a percutaneous cuffed technique and a locally developed scalpel bougie cricothyrotomy technique. After lectures, pre-tests in both techniques on isolated porcine models were performed. After hands-on training, only a post-test in technique of preference was performed. An important theme in the program is the allowance of making complications during training. Participants are trained how to recognize, acknowledge and handle errors and complications. The models used, allow for the making and assessment of errors and complications. Another important theme is reflection on personal beliefs, learning points and conscious decision making. Aim of the study was to evaluate direct results of the educational program and include safety and efficacy considerations of the techniques. Data on performance, self appraisal scores and technique of preference were collected before, during and after the course. Latest results will be presented. 1 During our educational programs, we have observed specific errors leading to specific complications. This, and the wish to develop models to train and maintain skilled on in any work environment, have led to two other studies. Based on the occurrence of intratracheal extraluminal false passage in porcine models, an exploratory anatomical study was done to test whether a lateral entrance point at the level of the cricothyroid membrane (error) could lead to intratracheal extraluminal false passage (complication) in human cadaveric model as well. Mechanisms were studied using isolated cadaveric human and porcine models and literature., hypothesis on mechanism causing the complication and potential consequences for training and clinical practice will be presented. 2 A technical descriptive study was performed, aimed at developing features for 3D printed FONA models for different parts of training procedural skills. We evaluated available 3D models for their edu- Abstracts wetenschapsdag

30 Abstracts Perioperative Medicine cational abilities and used our educational research results. The development process and realization of the concept model, that enables making errors and complications, will be discussed. 3 from our studies have demonstrated the potential importance of entering the airway via the midline. As assessment of the infraglottic airway by inspection and palpation alone can be challenging, clinical cases were collected to illustrate the added value of preemptive 3D virtual endoscopy and ultrasound in severe neck pathology. Airways can be straightforward, deviated and or rotated (figure1) and this will change position of the midline of the airway and the location of a functional incision for (e) FONA, if needed. Parts of the case series will be presented to demonstrate the use of imaging in preparing for clinical decision making. 4 Preliminary results from the educational program from were, in part, presented as abstract, during European Airway Congress in Berlin Bruijstens L, Lammers M, Scheffer GJ, Fluit CRMG, van den Hoogen FJA, Steegers MAH. Creating confident and competent professionals in cricothyrotomy. A course to enhance conscious decision making. All studies have been performed in accordance with local ethical guidelines. Abstracts wetenschapsdag