Nederlands tijdschrift voor anesthesiologie 4 · NTvA 2017; 30: 122 nederlands tijdschrift voor...

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Wetenschapsspecial volume 30, september 2017 4 anesthesiologie Nederlands tijdschrift voor Officiële uitgave van de Nederlandse Vereniging voor Anesthesiologie Prof. Dr. E.A.J. Joosten, hoofdredacteur • Een beetje trots E.A.J. Joosten • Continuïteit C. Boer • Genetica en perioperative medicine. Deel 3 : genetische screening, nociceptie en pijn in zebravissen R.R.I. van Reij, I. Eijkenboom, J. Vanoevelen, D.M.N. Hoofwijk, E.A.J. Joosten, N.J. van den Hoogen Abstracts 14de Wetenschapsdag Sessie 1: 6 abstracts Sessie 2: 3 abstracts Sessie 3: 6 abstracts Sessie 4: 3 abstracts

Transcript of Nederlands tijdschrift voor anesthesiologie 4 · NTvA 2017; 30: 122 nederlands tijdschrift voor...

Page 1: Nederlands tijdschrift voor anesthesiologie 4 · NTvA 2017; 30: 122 nederlands tijdschrift voor nederlands tijdschrift voor anesthesiologie| september ’17 Wetenschapsdag - september

Wetenschapsspecial

volume 30, september 2017 4

anesthesiologieNederlands tijdschrift voor

Officiële uitgave vande Nederlandse Verenigingvoor Anesthesiologie

Prof. Dr. E.A.J. Joosten, hoofdredacteur

• Een beetje trotsE.A.J. Joosten

• ContinuïteitC. Boer

• Genetica en perioperative medicine. Deel 3 : genetische screening, nociceptie en pijn in zebravissen R.R.I. van Reij, I. Eijkenboom, J. Vanoevelen, D.M.N. Hoofwijk, E.A.J. Joosten, N.J. van den Hoogen

Abstracts 14de WetenschapsdagSessie 1: 6 abstractsSessie 2: 3 abstractsSessie 3: 6 abstractsSessie 4: 3 abstracts

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anesthesiologieNederlands tijdschrift voor

inhoud

programma wetenschapsdag 2017 122

editorial 124Een beetje trotsE.A.J. Joosten

editorial 125Continuïteit C. Boer

onderzoek 139Genetica en perioperative medicine Deel 3 : genetische screening, nociceptie en pijn in zebravissen R.R.I. van Reij, I. Eijkenboom, J. Vanoevelen, D.M.N. Hoofwijk, E.A.J. Joosten, N.J. van den Hoogen

september ’17 | nederlands tijdschrift voor anesthesiologie 121

sessie 1 - 15 m i n 126

On demand versus deep neuromuscular relaxation in patients undergoing thoracolaparoscopic esophagectomy - a randomized controlled trialJ.A. Bosman, D.P. Veelo, S.S. Gisbertz, J.M. Binnekade, R.A. Hannivoort, M.I. van Berge Henegouwen B.F. Geerts, M.W. Hollmann

sessie 1 - 10 m i n 126

Genetic polymorphisms within the gene encoding Catechol-O-methyltransferase (COMT) are associated with prevalence of Chronic Post-Surgical Pain after HysterectomyR.R.I. van Reij, N.J. van den Hoogen, B.P. Rutten, G. Kenis, E. A. Joosten, W.F.F.A. Buhre, D.M.N. Hoofwijk

sessie 1 - 10 m i n 127

SGLT2i inhibit NHE, reduce [Na+]c and activate vasorelaxation in isolated mouse cardiomyocytes/hearts, but only EMPAgliflozin (EMPA) increases glucose consumptionL. Uthman, A. Baartscheer,

B. Bleijlevens, C.A. Schumacher,

J.W.T. Fiolet, A. Koeman, M.W. Hollmann,

N.C. Weber, R. Coronel, C.J. Zuurbier

sessie 1 - 1 0 m i n 128

On demand versus deep neuromuscular relaxation in patients undergoing thoracolaparoscopic

esophagectomy A randomized controlled trialS.T. Idzinga, A.M. Sauër

ses sie 2 - 10 min 129

Priming of the developing nociceptive system: Long-term consequences of pain in early lifeN.J. van den Hoogen, R.R.I. van Reij, J. Patijn, D. Tibboel, M. Fitzgerald, C. Kwok, E.A.J. Joosten,

ses sie 2 - 15 min 129

Therapeutic effect of two different alpha-adrenergic receptor antagonists during pheochromocytoma surgery PRESCRIPT an interim analysisM.F. Voogd, E. Buitenwerf, T.E. Osinga, H.J.L.M. Timmers, J.W.M. Lenders, R.A. Feelders, E.M.W. Eekhoff, H.R. Haak, E.P.M. van der Kleij-Corssmit, T.P. Links, N. Alagla, J.K.G. Wietasch, M.N. Kerstens

ses sie 2 - 15 min 130

Remote monitoring of vital functions to predict postoperative pulmonary complications after abdominal surgeryS.G. Plug, R.W. Touw, W.H. van der Ven, P.R. Tuinman, P. Schober, C. Boer

ses sie 2 - 10 min 131

Involvement of anesthesiology in perioperative care in oncologic Head-and-Neck surgeryD.H.K. Flipse, J.M.K. van Fessem, S.E. Hoeks, A. Sewnaik, R.J. Baatenburg-de Jong, R.J. Stolker

sessie 2 - 10 min 131

Current perioperative management of patients with diabetes mellitus in Dutch hospitalsA.H. Hulst, P.F. Raps, J.A.W. Polderman, J.H. DeVries, M.W. Hollmann, B. Preckel, J. Hermanides

sessie 3 - 15 min 132

Effects of thoracic epidural anesthesia on the serosal microcirculation of the human intestineA. Tavy, A.F.J. de Bruin, K. van der Sloot, A. Smits, E.C. Boerma, P.G. Noordzij, D. Boerma, M. van Iterson

sessie 3 - 10 min 133

Troponin release after major non-cardiac surgery: from marker to eventK.H.J.M. Mol, S.E. Hoeks, R.J. Stolker, F. van Lier

sessie 3 - 10 min 133

The prevalence of chronic neuropathic pain in survivors of critical illness: an observational pilot studyW.K.M. van Os, M.E. Koster-Brouwer, O.L. Cremer, M. Rijsdijk

sessie 3 - 10 min 134

The effect of a glucocorticoid containing cardioplegia solution on mortality after cardiac surgery: a historical cohort studyM. Nouwen, S. Rigter, L. Miggelbrink, N. Saouti, P.G. Noordzij

sessie 3 - 10 min 135

Functional analysis of the c.38T>G (p.13Leu>Arg) RYR1 variant results this mutation to be listed as causative of Malignant HyperthermiaT. Greven, J.C.F. Koenen, E.J. Kamsteeg, M.M.J. Snoeck

sessie 3 - 15 min 135

Electrical stimulation of the forearm to induce venodilationM. van Lieshout, D.A.M. de Gier, L.T. van Eijk, C. Keijzer-Broeders

sessie 4 - 15 min 136

The two-faced action of CO2 on the cerebral vasculatureN.H. Sperna Weiland, J. Hermanides, M.W. Hollmann, B. Preckel, J.J. van Lieshout, W.J. Stok, R.V. Immink

sessie 4 - 15 min 137

Norepinephrine use contributes to intestinal damage in septic shock patientsQ.L.M. Habes, L. van Ede, J. Gerretsen, M. Kox, P. Pickkers

sessie 4 - 15 min 137

Spinal Morphine for laparoscopic segmental colonic resection (SALMON-trial); a randomized controlled trialM.V. Koning, A.J.W. Teunissen, E. van der Harst, L. Ruijgrok, R.J. Stolker

Abstracts 14de Wetenschapsdag

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NTvA 2017; 30:

122 nederlands tijdschrift voor anesthesiologie | september ’17122 nederlands tijdschrift voor anesthesiologie | september ’17

Wetenschapsdag - september 2017 programma

09.00 - 10.15 sessie 1

09.05 - 09.20

On demand versus deep neuromuscular relaxation in patients undergoing thoracolaparoscopic esophagectomy - a randomized controlled trialJ.A. Bosman, D.P. Veelo, S.S. Gisbertz, J.M. Binnekade, R.A. Hannivoort, M.I. van Berge Henegouwen, B.F. Geerts, M.W. Hollmann

- Academic Medical Center, Amsterdam

09.20 - 09.30

Genetic polymorphisms within the gene encoding Catechol-O-methyltransferase (COMT) are associated with prevalence of Chronic Post-Surgical Pain after HysterectomyR.R.I. van Reij 1,2, N.J. van den Hoogen 1,2, B.P. Rutten 2, G. Kenis 2, E. A. Joosten 1,2, W.F.F.A. Buhre 1, D.M.N. Hoofwijk

1 Department of Anesthesiology and Pain Medicine, Maastricht University Medical Center+, Maastricht

2 School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre, Maastricht

09.30 - 09.40

SGLT2i inhibit NHE, reduce [Na+]c and activate vasorelaxation in isolated mouse cardiomyocytes/hearts, but only EMPAgliflozin (EMPA) increases glucose consumptionL. Uthman 1, A. Baartscheer 2, B. Bleijlevens 3, C.A. Schumacher 2, J.W.T. Fiolet 2, A. Koeman 1, M.W. Hollmann 1, N.C. Weber 1, R. Coronel 2, C.J. Zuurbier 1

1 Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Academic Medical Center, Amsterdam

2 Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam

3 Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam

09.40 - 09.50

Hyponatriemia as a riskfactor for postoperative deliriumS.T. Idzinga, A.M. Sauër

- University Medical Center Utrecht

09.50 - 10.00

Priming of the developing nociceptive system: Long-term consequences of pain in early lifeN.J. van den Hoogen 1,2, R.R.I. van Reij 1,2, J. Patijn 1, D. Tibboel 3, M. Fitzgerald 4, C. Kwok 5, E.A.J. Joosten 1,2

1 Department of Anaesthesiology, Pain Management and Research Centre, Maastricht University Medical Centre

08.30 - 9.00 Ontvangst09.00 - 9.05 Opening door Wolfgang Schlack (AMC) en Christa Boer (VUmc)

2 Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University

3 Intensive Care and Department of Paediatric Surgery, Erasmus MC-Sophia, Rotterdam

4 Department of Neuroscience, Physiology and Pharmacology, University College London, London

5 Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary

10.00 - 10.15

Therapeutic effect of two different alpha-adrenergic receptor antagonists during pheochromocytoma surgery. PRESCRIPT an interim analysisM.F. Voogd 1, E. Buitenwerf 2, T.E. Osinga 2, H.J.L.M. Timmers 3, J.W.M. Lenders 3,4, R.A. Feelders 5, E.M.W. Eekhoff 6, H.R. Haak 7, E.P.M. van der Kleij- Corssmit 8, T.P. Links 2, N. Alagla 2, J.K.G. Wietasch 1, M.N. Kerstens 2 on behalf of the PRESCRIPT investigators

1 Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen

2 Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen

3 Department of Internal Medicine, Radboud University Medical Center Nijmegen

4 Department of Medicine III, Technische Universität Dresden, Dresden, Germany

5 Department of Endocrinology, Erasmus Medical Center, Rotterdam

6 Department of Endocrinology, Erasmus Medical Center, Rotterdam

7 Department of Internal Medicine, Máxima Medical Center, Eindhoven

8 Departments of Endocrinology, Leiden University Medical Center, Leiden

10.15 - 1.45

Pauze

09.00 - 10.15 sessie 2

10.45 - 11.30

Key note Lecture: Amir A. Ghaferi

11.30 - 11.45

Remote monitoring of vital functions to predict postoperative pulmonary complications after abdominal surgeryS.G. Plug, R.W. Touw, W.H. van der Ven, P.R. Tuinman, P. Schober, C. Boer

- VU University Medical Center

11.45 - 11.55

Involvement of anesthesiology in perioperative care in oncologic Head-and-Neck surgeryD.H.K. Flipse ¹, J.M.K. van Fessem ¹, S.E. Hoeks ¹, A. Sewnaik ², R.J. Baatenburg-de Jong ², R.J. Stolker ¹

1 Department of Anesthesiology, Erasmus Medical Center Rotterdam Bravis hospital

2 Department of Ear, Nose and Throat-medicine and Head-and-Neck surgery, Erasmus Medical Center Rotterdam

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11.55 - 12.05

Current perioperative management of patients with diabetes mellitus in Dutch hospitalsA.H. Hulst, P.F. Raps, J.A.W. Polderman, J.H. DeVries, M.W. Hollmann, B. Preckel, J. Hermanides

- Academic Medical Center, Amsterdam

12.05 - 13.05

Lunchpauze

13.05 - 14.05 sessie 3

13.05 - 13.20

Effects of thoracic epidural anesthesia on the serosal microcirculation of the human intestineA. Tavy 1, A.F.J. de Bruin 1, K. van der Sloot 1, A. Smits 2, E.C. Boerma 3, P.G. Noordzij 1, D. Boerma 2, M. van Iterson 1

1 Departments of Anesthesiology, Intensive Care and Cardiothoracic Surgery, St Antonius Hospital, Nieuwegein

2 Department of Anesthesiology and Pain Medicine, Haaglanden Medical Center, Den Haag

3 Department of Surgery, St. Antonius Hospital, Nieuwegein

13.20 - 13.30

Troponin release after major non-cardiac surgery: from marker to eventK.H.J.M. Mol, S.E. Hoeks, R.J. Stolker, F. van Lier

- Erasmus Medisch Centrum Rotterdam

13.30 - 13.40

The prevalence of chronic neuropathic pain in survivors of critical illness: an observational pilot studyW.K.M. van Os, M.E. Koster-Brouwer, O.L. Cremer, M. Rijsdijk

- University Medical Center Utrecht

13.40 - 13.50

The effect of a glucocorticoid containing cardioplegia solution on mortality after cardiac surgery: a historical cohort studyM. Nouwen, S. Rigter, L. Miggelbrink, N. Saouti, P.G. NoordzijSt. Antonius Ziekenhuis

13.50 - 14.00

Functional analysis of the c.38T>G (p.13Leu>Arg) RYR1 variant results this mutation to be listed as causative of Malignant HyperthermiaT. Greven 1,2, J.C.F. Koenen 1, E.J. Kamsteeg 2, M.M.J. Snoeck 1

MH Expertise Center Nijmegen:

1 CWZ

2 RadboudUMC

14.00 - 14.15

Electrical stimulation of the forearm to induce venodilationM. van Lieshout, D.A.M. de Gier, L.T. van Eijk, C. Keijzer-BroedersDepartment of Anesthesiology, Pain and Palliative Medicine, Radboudumc, Nijmegen

14.15 - 15.45

Pauze

14.45 - 16.00 sessie 4

14.45 - 15.00

The two-faced action of CO2 on the cerebral vasculatureN.H. Sperna Weiland 1,2, J. Hermanides 1, M.W. Hollmann 1, B. Preckel 1, J.J. van Lieshout 2,3, W.J. Stok 2, R.V. Immink 1,2

1 Department of Anaesthesiology, Academic Medical Centre AMC Amsterdam

2 Laboratory for Clinical Cardiovascular Physiology, Academic Medical Centre AMC Amsterdam

3 Department of Internal Medicine, Academic Medical Centre AMC Amsterdam University of Amsterdam, Amsterdam

15.00 - 15.10

Norepinephrine use contributes to intestinal damage in septic shock patientsQ.L.M. Habes, L. van Ede, J. Gerretsen, M. Kox, P. PickkersRadboud Nijmegen

15.10 - 15.25

Spinal Morphine for laparoscopic segmental colonic resection (SALMON-trial); a randomized controlled trialM.V. Koning 1,2, A.J.W. Teunissen 2, E. van der Harst 3, L. Ruijgrok 4, R.J. Stolker 1

1 Department of Anesthesiology, Erasmus Medical Center, Rotterdam

2 Department of Anesthesiology, Maasstad Hospital, Rotterdam

3 Department of Surgery, Maasstad Hospital, Rotterdam

4 Department of Pharmacology, Maasstad Hospital, Rotterdam

15.25 - 15.45

Young Investigator Grant winnaar 2014: Marieke NiestersLeiden University Medical Center

15.45 - 15.55

Uitreiking prijzen: Christa Boer (VUmc)

15.55 - 16.00

Afsluiting: Wolfgang Schlack (AMC)

16.00 - 17.00

Borrel

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editorial colofonHet 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 overzichts artikelen, klinische en laboratoriumstudies en casuïstiek, de verspreiding van kennis betreffende de anesthesiologie en gerelateerde vakgebieden te bevorderen.

REDACTIEHoofdredacteur: Prof. Dr. E.A.J. Joosten.Redacteuren: Dr. P. van Beest, Dr. J. Bijker, Dr. A. Bouwman, Dr. P. Bruins, Prof. Dr. A. Dahan, Dr. H. van Dongen, Dr.L.van Eijk, Dr. J.P. Hering, Dr. S. Dieleman, Dr. J.S. Jainandunsing,Prof. Dr. M.W. Hollmann, Dr. R.V. Immink, 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: Congresbureau Breener. T 026 202 20 63 / Email [email protected]

REDACTIE-ADRESNederlandse Vereniging voor AnesthesiologieDomus Medica, Mercatorlaan 1200, 3528 BL Utrecht; www.anesthesiologie.nl

INZENDEN VAN KOPIJRichtlijnen voor het inzenden van kopij vindt u op www.anesthesiologie.nl of kunt u opvragen bij de redactie of de uitgever: [email protected]

OPLAGE2.500 exemplaren, 5x per jaar

Het NTvA wordt uitsluitend toegezonden aan leden van de NVA. Adreswijzigingen: Nederlandse Vereniging voor Anesthesiologie, Postbus 20063, 3502 LB Utrecht, T 030-2823385, F 030-2823856, Email [email protected]

PRODUCTIEEldering Studios: Ontwerp: Dimitry de BruinEindredactie & bladcoördinatie: Monique de Mijttenaere

AUTEURSRECHT EN AANSPRAKELIJKHEIDNederlands Tijdschrift voor Anesthesiologie® is een wettig gedeponeerd woordmerk van de Ne-derlandse 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 foto kopieën, opnamen of enige andere manier, zonder vooraf-gaande schriftelijke toestemming.

Geachte lezer,

Elk jaar zie ik uit naar de bijdragen en ab-stracts voor onze Weten-schapsdag. En net als vo-rige jaren ben ik wederom blij verrast met de hoge kwaliteit en diversiteit van die abstracts. Het blijft toch mooi dat een relatief klein land als Nederland zulk een goede en hoge kwaliteit anesthesiologisch onderzoek kan blijven leveren. Daar mogen we met zijn allen best een beetje trots op zijn. Natuurlijk wens ik alle kandidaat-sprekers op deze Wetenschapsdag (29 september te Amsterdam) veel succes.

Daarnaast verdienen de lokale organisa-toren (collegae Christa Boer - VUMC, Markus Hollmann - AMC, Stephan Loer - VUmc, Wolfgang Schlack - AMC en Benedikt Preckel - AMC) een groot compliment met zo’n mooi pro-gramma. Ik ben ervan overtuigd dat het samenkomen van onderzoekers op zo’n dag alleen maar stimulerend kan werken en verder top-onderzoek zal initiëren. Ik nodig u dan ook uit om de abstracts van deze bijdragen te lezen en daarmee een beeld te vormen van het

huidige onderzoek binnen de Anesthesiologie en Pijnbe-strijding in Nederland. De abstracts geven daarnaast een beeld in welke richting het onderzoek (en daarmee ook de kliniek van de toekomst) zich beweegt.

Naast de abstracts voor de 14e Wetenschapsdag in dit issue een onderzoeksartikel uit de reeks Genetica en perioperative medicine (bijdrage van Roel van Reij en collega’s van het MUMC+ Maastricht). Hoe wordt er genetisch onderzoek gedaan? Wat kunnen we er mee (en wat niet!)? In deze (3e) bijdrage uit de reeks wordt specifiek ingegaan op de vraag op welke manier de zebravis kan worden ingezet om inzicht te krijgen in gemu-teerde genen die het chronificeren van pijn kunnen voorspellen. Dit ‘state of the art’ artikel alsmede de abstracts van de Wetenschapsdag moeten volgens mij genoeg prikkelende informatie bevatten om eens rustig voor te gaan zitten.

Ik wens u, namens de gehele redactie, veel leesplezier,

Bert Joosten, hoofdredacteur

Een beetje trots

E.A.J. Joosten, Prof. Dr.Hoofdredacteur NTvAMaastricht [email protected]

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Geachte lezer,

Nadat in 2004 de 1e NVA Weten-schapsdag in Arnhem plaatsvond, heeft

Amsterdam in de paar jaar daarna als gastheer voor deze dag opgetreden. Het is voor ons dan ook bijzonder dat Amsterdam na een pauze van 10 jaar de 14e editie van de Wetenschapsdag mag verzorgen.

Wanneer we terugblikken op de afgelopen 10 jaar wetenschap binnen het anesthesiologisch werkveld hebben er veel ontwikkelingen plaats-gevonden. Niet alleen het aantal en de kwaliteit van wetenschappelijke publicaties namen toe, maar er wordt ook steeds meer samengewerkt in onderzoeksconsortia om belangwekkende klini-sche vraagstukken te beantwoorden. Daarnaast belooft de toename van het aantal gepromo-veerde collega’s dat er kan worden gebouwd aan klinische zorg die wordt gesteund door weten-schappelijk bewijs, en aantoonbare waarde heeft voor de patiënt en maatschappij.

Toen wij mochten nadenken over een Key Note spreker voor de Wetenschapsdag kwamen wij al gauw uit op Dr. Amir Ghaferi. Dr. Ghaferi staat aan de basis van het failure-to-rescue concept binnen de postoperatieve periode. In de publi-caties van Dr. Ghaferi komt naar voren dat de kans op ernstige postoperatieve complicaties en intensivering van zorg toeneemt wanneer de opvang van milde verstoringen in de gezondheid van geopereerde patiënten niet structureel en

planmatig wordt aangepakt. Het waarborgen van de continuïteit van perioperatieve zorg is dan ook één van de grote uitdagingen binnen het anesthesiologisch en chirurgisch werkveld.

Continuïteit speelt ook een belangrijke rol in de wetenschap. Om deze te waarborgen is het onze taak om jonge studenten, artsen en niet-artsen te motiveren om hun opleiding te combine-ren met wetenschappelijk onderzoek. Jonge gepromoveerden zijn de opleiders, hoogleraren en afdelingshoofden van later, en het koesteren, begeleiden en stimuleren van hun loopbaan is dan ook één van onze kerntaken.

De NVA Wetenschapsdag is ooit opgezet om juist deze jonge collega’s een platform te bieden om hun werk met u te delen. We zijn dan ook zeer verheugd dat tijdens deze editie het programma opnieuw gevuld is met jonge talenten die een doorsnede van de actualiteiten binnen het anes-thesiologisch werkveld zullen presenteren.

We wensen u veel plezier op 29 september!

Namens het organiserend comité NVA Wetenschapsdag 2017

Markus Hollmann (AMC)Stephan Loer (VUmc)Benedikt Preckel (AMC)Wolfgang Schlack (AMC)Christa Boer (VUmc)

editorialC. Boer, Prof. Dr. VUmc

Continuïteit

september ’17 | nederlands tijdschrift voor anesthesiologie 125

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abstracts 2017126 nederlands tijdschrift voor anesthesiologie | september ’17

SESSI E 1 - 15 min

On demand versus deep neuromuscular relaxation in patients undergoing thoracolaparoscopic esophagectomy - a randomized controlled trialJ.A. Bosman, D.P. Veelo, S.S. Gisbertz, J.M. Binnekade, R.A. Hannivoort, M.I. van Berge Henegouwen B.F. Geerts, M.W. Hollmann

Academic Medical Center, Amsterdam

IntroductionDeep neuromuscular block (NMB) can im-prove surgical conditions and pain during laparoscopic surgery. We hypothesized that deep as compared to an on demand (mod-erate) NMB regime also improves surgical conditions in patients undergoing thoraco-laparoscopic esophagectomy.

MethodsSingle-center, randomised controlled, dou-ble blind trial. Patients were randomized to continuous infusion of rocuronium 0.6 mg/kg/hr (deep) or NaCl 0.9% (on demand). Both the surgeon and anaesthesiologist

were blinded for randomization and train-of-four (TOF) measurements. Open label Rocuronium was given if requested. SRS, a 5-point rating scale (1 = extremely poor, 5 = optimal), was taken every 30 minutes and after a bolus Rocuronium. At the end of surgery, sugammadex was given if appropri-ate. Primary outcome parameter was SRS. Secondary outcome parameters were mor-bidity, adverse events, pain, and duration of operation. Data are in mean (SD) or median (IQR).

ResultsObserved mean SRS was equal between groups (4.1 (0.5) vs. 4.0 (0.5), p=.50). More rocuronium was requested in the on de-mand group (2.4(1.6) vs 4.1(1.9) times, p<.01). Multiple linear regression analysis showed lower mean SRS in the “on demand” group when corrected for TOF and posi-

tion (beta(95CI): -0.5 (-0.8 to -0.1), p=.01). A greater proportion of patients in the on demand group had postoperative cardiac events 2(6) vs. 10(30)%, p=.01). There were no differences in adverse events and pain scores. The deep NMB group received more sugammadex (650(305-1464) vs. 200 (140-240) mg, p <.01). There was no effect on duration of operation.

ConclusionIn the context of this trial deep NMB did not improve SRS in patients undergoing thoracolaparoscopic esophagectomy. How-ever, the difference in the rocuronium bolus requests did imply an effect on perceived operating conditions. There was a decrease in postoperative cardiac events, other ben-efits were not found.

SESSI E 1 - 10 min

Genetic polymorphisms within the gene encoding Catechol-O-methyltransferase (COMT) are associated with prevalence of Chronic Post-Surgical Pain after HysterectomyR.R.I. van Reij 1,2, N.J. van den Hoogen 1,2, B.P. Rutten 2, G. Kenis 2, E. A. Joosten 1,2, W.F.F.A. Buhre 1, D.M.N. Hoofwijk 1

1 Department of Anesthesiology and Pain Medicine, Maastricht University Medical Center+, Maastricht

2 School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre, Maastricht

IntroductionChronic postsurgical pain (CPSP) is a com-mon problem affecting 10 to 60% of all surgi-cal patients. Although demographic, clinical and psychological risk factors are well docu-mented; little is known about genetic risk factors for CPSP. A systematic review by our group has identified several single nucleotide polymorphisms (SNPs) associated with CPSP (Hoofwijk et al., 2016, BJA). SNPs studied

by different groups were selected as SNPs of interest. The aim of this study is to investi-gate the association between these SNPs of interest and the prevalence of CPSP.

MethodsWe conducted a genome-wide association study in a prospective cohort study of 500 hysterectomy patients. The primary outcome was the association between CPSP (defined as Numeric Rating Scale ≥ 4) 3 and 12 months after hysterectomy and SNPs in the OPRM1, GCH1, CACNG2, KCNS1 and COMT genes. Association testing for the SNPs of interest was done via logistic regression.

ResultsAfter quality control 345 patients out of 500 were included. 34 patients out of 345 (9,8%) met the criteria for CPSP at three months

after hysterectomy. Multiple SNPs within COMT gene were significantly associated with CPSP at 3 months after hysterectomy. No significant associations between the other SNPs and CPSP at 3 months were found and no SNP was significantly associated with CPSP at 12 months after hysterectomy.

ConclusionGenetic variation within the COMT gene was associated with CPSP in a cohort of hys-terectomy patients at 3 months after the sur-gery. This finding is important in discovering the relationship between genetic variation and the biological and psychological mecha-nisms of CPSP. One of the possible future directions is incorporating these findings in a clinical relevant prediction model for CPSP together with already established clinical, demographic and psychological risk factors.

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SGLT2i inhibit NHE, reduce [Na+]c and activate vasorelaxation in isolated mouse cardiomyocytes/hearts, but only EMPAgliflozin (EMPA) increases glucose consumptionL. Uthman 1, A. Baartscheer 2, B. Bleijlevens 3, C.A. Schumacher 2, J.W.T. Fiolet 2, A. Koeman 1, M.W. Hollmann 1, N.C. Weber 1, R. Coronel 2, C.J. Zuurbier 1

1 Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Academic Medical Center, Amsterdam

Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam

3 Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam

IntroductionSGLT2 inhibitors (SGLT2i) are a novel class of type 2 diabetes drugs that show unexpected cardiac benefits, which cannot be explained by reduction in general cardiovascular risk factors. We recently showed that SGLT2i EMPA reduces cardiac [Na+]c and [Ca2+]c and inhibits sodium hydrogen exchanger 1 (NHE-1). Here, we investigate 1) how SGLT2i can interact with NHE, 2) whether two other SGLT2i inhibitors (dapagliflozin (DAPA)

and canagliflozin (CANA)) block cardiac NHE and reduce [Na+]c as well, and 2) how SGLT2i affect performance of the isolated healthy heart.

MethodsIn silico docking studies on NHE-1 in the presence of SGLT1i were performed. Experiments were conducted in the presence of 1 µM EMPA, 1 µM DAPA, 3 µM CANA or vehicle. NHE activity and [Na+]c were assessed in C57Bl/6N mice cardiomyocytes exposed to SGLT2i. Furthermore, healthy Langendorff-perfused mouse hearts were subjected to SGLT2i for 30 minutes and cardiac hemodynamics, metabolism (glucose/oxygen consumption) and energetics (PCr/ATP) were determined.

ResultsDocking studies predicted that all three compounds bind with relatively high binding affinity to the extracellular Na+-binding site of NHE-1. Moreover, all three SGLT2i inhibited NHE compared to vehicle

(7.09±0.04), with EMPA showing the strongest inhibition of NHE (1 µM EMPA 6.69±0.03, p<0.001; 1 µM DAPA 6.77±0.04, p<0.001; 3 µM CANA; 6.80±0.07, p<0.05). Furthermore, all three SGLT2i significantly lowered [Na+]c (EMPA: 10.0±0.2, DAPA: 10.7±0.2 and CANA: 11.0±0.3 vs. vehicle: 12.7±0.3 mM). Finally, in Langendorff-perfused mouse hearts, EMPA and CANA reduced perfusion pressure by 20% (p<0.05), and only EMPA increased cardiac glucose consumption.

ConclusionEMPA, DAPA and CANA inhibit cardiac NHE and lower [Na+]c, however to different degrees. EMPA and CANA activate vasodilation in intact hearts, but only EMPA increases glucose consumption.

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SESSIE 1 - 10 min

On demand versus deep neuromuscular relaxation in patients undergoing thoracolaparoscopic esophagectomy A randomized controlled trialS.T. Idzinga, A.M. Sauër

University Medical Center Utrecht

IntroductionPopstoperative delirium (POD) is a serious compliction of surgery, that might have long-term cognitive and functional consequences. Many perioperatieve riskfactors have been investigated. Among them preoperative ele-ktrolyte disturbances. However, definitions vary among different studies. For this study we chose to focus on sodium levels and the relation of hyponatriemia and POD for two different cutt-off points of sodium.

MethodsThis is a post-hoc analysis of prospectively collected data from a single-center sub-study within a larger, multicenter placebo

controlled randomized clinical trial, the Dexamethasone for Cardiac Surgery (DECS) trial. The first preoperativeserum sodium value from the admission or if not available the value from the (outpatient) preoperative screening was extracted from the digital hos-pital laboratory registration. Hyponatriemia was defined as 1) any value lower than the normal values of 135-145mmol/L, or 2) lower than 130mmol/L the clinical cutt-off chosen as acceptable for anesthesia. Delirium was defined acoording to a previously published, validated protocol including the CAM-ICU, chart revision and use of Haloperidol.

ResultsBasline demographic, clinical and surgi-cal characteristics of the 737 subjects were balanced among hypo- and nonhyponatri-

emia groups. 72 Patients had a natrium of <135mmol/L, 6 patients of <130mmol/L. 107 Patients were diagnosed with delirium. Univariate logistic regression analysis of the relation between hyponatriemia (both defi-nitions) and delirium showed no clinically significant difference (Na<135mmol/L OR 1.20 95% confidence interval (CI) 0.62-2.32 p=0.58; Na<130mmol/L OR 1.18 95% CI 0.14-10.2 p=0.88), multivariate regression analysis did not change our results.

ConclusionIn our cardiac surgery population we could not show an independent relation between preoperative hyponatriemia and postopera-tive delirium. However both incidences of hyponatriemia and delirium were small com-pared to previous studies.

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Therapeutic effect of two different alpha-adrenergic receptor antagonists during pheochromocytoma surgery PRESCRIPT an interim analysisM.F. Voogd 1, E. Buitenwerf 2, T.E. Osinga 2, H.J.L.M. Timmers 3, J.W.M. Lenders 3,4, R.A. Feelders 5, E.M.W. Eekhoff 6, H.R. Haak 7, E.P.M. van der Kleij-Corssmit 8, T.P. Links 2, N. Alagla 2, J.K.G. Wietasch 1, M.N. Kerstens 2 on behalf of the PRESCRIPT investigators

1 Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen

2 Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen

3 Department of Internal Medicine, Radboud University Medical Center Nijmegen

4 Department of Medicine III, Technische Universität Dresden, Dresden, Germany

5 Department of Endocrinology, Erasmus Medical Center, Rotterdam

6 Internal Medicine, Endocrinology Section, VU

University Medical Center, Amsterdam7 Department of Internal Medicine, Máxima Medical

Center, Eindhoven8 Departments of Endocrinology, Leiden University

Medical Center, Leiden

IntroductionAdministration of alpha-adrenergic receptor antagonist is recommended before resection of a pheochromocytoma (PCC) in order to prevent perioperative cardiovascular com-plications. We conducted the first random-ized controlled trial comparing the efficacy of phenoxybenzamine (PXB) or doxazosin (DOX) in controlling perioperative hemo-dynamics in patients undergoing PCC resec-tion (ClinicalTrials.gov: NCT01379898).

MethodsPatients >18 years with a PCC were random-ized to pretreatment with either PXB or DOX. Preoperative BP targets were: <130/80 mmHg (supine) and SBP 90-110 mmHg (up-right). Metoprolol was added if heart rate was >80/min (supine) or >100/min (upright). Anesthetic procedures were standardized. Primary endpoint was the frequency of intraoperative hemodynamic episodes out-side the target range (i.e. MAP<60 mmHg or SBP>160 mmHg). Data are presented as mean ± SD or median [IQR]. A two-sided P-value <0.05 was considered significant.

SESSI E 2 - 10 min

Priming of the developing nociceptive system: Long-term consequences of pain in early lifeN.J. van den Hoogen 1,2, R.R.I. van Reij 1,2, J. Patijn 1, D. Tibboel 3, M. Fitzgerald 4, C. Kwok 5, E.A.J. Joosten 1,2

1 Department of Anaesthesiology, Pain Management and Research Centre, Maastricht University Medical Centre

2 Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University

3 Intensive Care and Department of Paediatric Surgery, Erasmus MC-Sophia, Rotterdam

4 Department of Neuroscience, Physiology and Pharmacology, University College London, London

5 Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary

IntroductionClinical and experimental data suggests that noxious stimulation at critical stages of development has both short- and long-term consequences on nociceptive processing in later life and might be an underlying cause of chronic persistent pain. Here, we use a rat model of repeated procedural pain as would be experienced clinically, to assess long-term changes in pain sensitivity and nociceptive processing.

MethodsNeonatal rats received four needle pricks per day in the left hind-paw from postnatal day 0 to 7 as a model of procedural pain in infancy. At young adult age, all animals received an ipsilateral hind-paw incision as a model for post-operative pain in adulthood. The effect of neonatal injury on adult pain behaviour, spinal anatomy and spinal nociceptive func-tionality was assessed.

ResultsNeonatal repetitive procedural pain (NPP) resulted in short-term increases in mechani-cal hypersensitivity of the ipsilateral hind-paw, but by adulthood, baseline sensitivity does not differ from controls. Following re-injury of the same dermatome, NPP leads to an increased duration of post-operative pain in adulthood. Moreover, the spinal cord dor-sal horn neurons, specifically Wide Dynamic Range (WDR) neurons show alterations in activity in adulthood after NPP evoked by different stimulation modalities (manuscript in preparation). Multiple molecular markers in the spinal cord might play an important

role during early priming of the nociceptive response. An increase in pain fibre specific marker Calcitonin-Gene Related Peptide was shown before. Immunocytochemical analy-sis revealed no differences in expression of Opioid Receptor µ1 OPRM1 in adult animals which underwent neonatal repetitive proce-dural pain. After paw incision, the expression of OPRM1 decreased in neonatal repetitive procedural pain animals, but not in control.

ConclusionNPP primes the spinal nociceptive circuits during development, and results in long-lasting anatomical and functional changes of this network which relates to altered pain behaviour.

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ResultsThis interim analysis includes 87 of 134 patients, aged 55 ± 16 years. Pretreatment with either DOX or PXB was administered to 44 (51%) and 43 (49%) patients, in a dose of 36 [28-48] mg and 120 [62.5-140] mg, re-spectively. Metoprolol was initiated in 63% and 86% of the patients on DOX or PXB (P=0.014). The number of intraoperative BP episodes outside target range was 4 [3-8] per patient in the DOX group and 4 [2-8] in the

PXB group (NS), with a total duration of 14 [6-17] and 12 [5-27] minutes (NS). The num-ber of different vasodilators administered during surgery was significantly higher in the DOX-group during the entire intraop-erative period (P=0.032) as well as after adre-nal vein ligation (P=0.049).

ConclusionThe preliminary results of this RCT do not demonstrate a difference in intraoperative

hemodynamic stability during PCC resec-tion between the two alpha-adrenergic receptor antagonists, though the number of different vasodilators administered was significantly higher in the DOX-group and reflex tachycardia occurred more frequently in the PXB-group.

SESSI E 2 - 15 min

Remote monitoring of vital functions to predict postoperative pulmonary complications after abdominal surgeryS.G. Plug, R.W. Touw, W.H. van der Ven, P.R. Tuinman, P. Schober, C. Boer

VU Medical Center, Amsterdam

IntroductionDetection of early changes in the respiratory rate (RR), oxygen saturation (SpO2) and pulse rate (PR) by remote monitoring may be valuable in the prevention of postopera-tive pulmonary complications (PPCs) at the surgical ward. In this study we investigated whether early postoperative deterioration of vital functions assessed by remote moni-toring could predict the development of PPCs.

MethodsThis study included patients undergoing major abdominal surgery with an increased

preoperative risk for PPCs (ARISCAT ≥26). The RR, SpO2, PR and a Modified Early Warning Score based on RR, SpO2 and PR (remMEWS) were continuously monitored for four postoperative days (POD). The predictive value of an SpO2<95%, RR <9 and >14 breaths/min, PR <51 and >100 beats/min and a remMEWS >3 measured on POD1 for the development of PPCs was calculated by a receiving operating characteristic (ROC) curve.

ResultsThirty out of 97 patients developed one or more PPCs on POD 2-4. Early changes in the SpO2 were found to be the best predictor of postoperative PPCs (AUC = 0.704, 95% CI, 0.559-0.808), followed by the RR (AUC = 0.664, 95%CI, 0.551-0.778) and remMEWS (AUC = 0.675 , 95% CI, 0.559-0.792). Chang-

es in PR had no predictive value for PPCs. An average remMEWS hour value of ≥3 oc-curred in 9.8% of the measurement time in PPC patients, compared to 3.3% of the time in non-PPC patients (P<0.001).

ConclusionThis study shows that the remMEWS on POD1 was more frequently disturbed in patients who developed PPCs compared to patients without PPCs. The SpO2 revealed to be a better predictor for PPCs than the RR or PR. Our study suggests that postoper-ative remote monitoring of vital paramaters may be useful in the early detection of PPCs.

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Involvement of anesthesiology in perioperative care in oncologic Head-and-Neck surgeryD.H.K. Flipse ¹, J.M.K. van Fessem ¹, S.E. Hoeks ¹, A. Sewnaik ², R.J. Baatenburg-de Jong ², R.J. Stolker ¹

¹ Department of Anesthesiology, Erasmus Medical Center Rotterdam

² Department of Ear, Nose and Throat-medicine and Head-and-Neck surgery, Erasmus Medical Center Rotterdam

IntroductionRecently, there has been an increasing in-terest for the patient-centered care model called Perioperative Surgical Home (PSH), in which multi-specialty care teams aim to improve surgical care and simultaneously control its costs. We believe that anesthesi-ologists can play a vital role in PSH through their extensive knowledge of perioperative care.

Therefore, this study assessed the role of an anesthesiologist as perioperative physician

on post-surgical outcomes in patients un-dergoing a Combined Mandibular Opera-tion.

MethodsAt the Head-and-Neck department of Erasmus Medical Center Cancer Institute, PSH was embodied by an anesthesiolo-gist, coordinating surgical care, attending grand rounds and training junior residents. A retrospective observational study was conducted with data derived from a pre intervention group (PRE-PSH group, N = 245) and compared with data from a post intervention group (POST-PSH group, N = 158). Follow-up was conducted until the day of hospital discharge.

ResultsIn the POST-PSH group, median length of stay tended to shorten by one day towards 14 days (IQR 12 17) vs. 15 days (13 - 19) in the

PRE-PSH group (p= 0.09). Furthermore, less patients tended to suffer from pneumonia in the POST-PSH group compared to the PRE-PSH group (22% vs. 30%, p= 0.09). No differ-ences between groups were found regarding complications as pulmonary embolism (0% vs. 1%), cardiac ischemia (1% vs. 1%), atrial fibrillation (6% vs. 7%), cerebrovascular accident (1% vs. 2%), ICU-admission (13% vs. 17%), severe complication/death (15% vs. 18%). ASA-risk classification was equally distributed within groups (p= 0.47).

ConclusionPerioperative involvement of an anesthesi-ologist might be supportive in improving quality of surgical care and thereby poten-tially reducing its costs. However, more re-search with a larger number of patients has to be conducted.

SESSI E 2 - 10 min

Current perioperative management of patients with diabetes mellitus in Dutch hospitalsA.H. Hulst, P.F. Raps, J.A.W. Polderman, J.H. DeVries, M.W. Hollmann, B. Preckel, J. Hermanides

Academic Medical Center, Amsterdam

IntroductionEvidence regarding the optimal treatment of patients with diabetes mellitus in the perioperative period is scarce and variable. We surveyed diabetes protocols in Dutch hospitals hypothesizing that these would show considerable variability, reflecting the diverse literature on this topic.

MethodsWe contacted all hospitals in the Neth-erlands by phone and (e-)mail to request their perioperative treatment protocol for patients with diabetes mellitus. In addition, we sent out a survey to gather information on preoperative preparation, diabetes medi-cation management, glucose measurements and glucose targets, potassium co-adminis-tration and blood sugar control-strategies.

ResultsOut of the 80 hospitals in the Netherlands, 70 responded to our request (response rate: 88%). We received 39 protocols, 18 hospitals answered the questions in our survey, and 13 hospitals provided both. The median up-per glucose target was 10 mmol l-1 (range 6-20), whereas the median lower target was 4 mmol l-1 (range 2-8). Long acting insulin is reduced by 25-50 % on the day before surgery in 26 hospitals (38%) and continued in full dosage in the others. On the day of surgery, insulin is stopped in 42 hospitals (60%), in 6 (9%) insulin is continued as normal, and in the remaining 13 (22%) the insulin dose is reduced by 25-66%. The glu-cose measurement interval varies between 1-6 times per hour, or is left to discretion of the anaesthesiologist. Forty-nine (70%) hospitals prescribe a peroperative glucose infusion (2-10 g h-1), 46 (66%) also adminis-ter continuous insulin (0.5-3 IE h-1), and 23 (33%) co-administer potassium (0.8-6 mmol h-1).

ConclusionOut of the 80 hospitals in the Netherlands, 70 responded to our request (response rate: 88%). We received 39 protocols, 18 hospitals answered the questions in our survey, and 13 hospitals provided both. The median up-per glucose target was 10 mmol l-1 (range 6-20), whereas the median lower target was 4 mmol l-1 (range 2-8). Long acting insulin is reduced by 25-50 % on the day before surgery in 26 hospitals (38%) and continued in full dosage in the others. On the day of surgery, insulin is stopped in 42 hospitals (60%), in 6 (9%) insulin is continued as normal, and in the remaining 13 (22%) the insulin dose is reduced by 25-66%. The glu-cose measurement interval varies between 1-6 times per hour, or is left to discretion of the anaesthesiologist. Forty-nine (70%) hospitals prescribe a peroperative glucose infusion (2-10 g h-1), 46 (66%) also adminis-ter continuous insulin (0.5-3 IE h-1), and 23 (33%) co-administer potassium (0.8-6 mmol h-1).

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SESSI E 3 - 15 min

Effects of thoracic epidural anesthesia on the serosal microcirculation of the human intestineA. Tavy 1, A.F.J. de Bruin 1, K. van der Sloot 1, A. Smits 2, E.C. Boerma 3, P.G. Noordzij 1, D. Boerma 2, M. van Iterson 1

1 Department of Anesthesiology, Intensive Care and Pain Medicine, St Antonius Hospital, Nieuwegein

2 Department of Anesthesiology and Pain Medicine, Haaglanden Medical Center, Den Haag

3 Department of Surgery, St. Antonius Hospital, Nieuwegein

4 Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden

IntroductionThe effect of thoracic epidural analgesia (TEA) on splanchnic blood flow during ab-dominal surgery remains unclear. The pur-pose of this study was to examine in patients if hemodynamic effects of TEA administra-tion resulted in microcirculatory alterations of the human intestinal serosa using Inci-dent Dark Field (IDF) videomicroscopy.

MethodsAn observational cohort study was per-formed. In eighteen patients the microcir-culation of the human intestinal serosa was visualized with IDF (see figure 1). Microcir-

culatory and hemodynamic measurements, were performed prior to (T1) and after a bolus (T2) of levobupivacaine had been given. If correction of blood pressure was in-dicated a third measurement was performed (T3). The following microcirculatory pa-rameters were calculated: microvascular flow index(MFI), proportion of perfused

vessels(PPV), perfused vessel density(PVD) and total vessel density(TVD). Data are pre-sented as median[IQR] or mean ± SD.

ResultsAt T1 mean (MAP, mmHg) and systolic (SBP, mmHg) arterial pressure were significant decreased versus T2 (MAP 76(±13) vs 63(± 11), SBP 118± (18) vs 80 (±87)). Microcircula-tory parameters of the bowel serosa how-ever, were unaltered. In seven patients blood pressure was corrected to baseline values (T3),while microcirculatory parameters (MFI, PPV, PVD and TVD) remained con-stant (see figure 2).

ConclusionWe examined the effects of TEA on the in-testinal serosal microcirculation during ab-dominal surgery using IDF imaging for the first time in patients. Regardless of a marked decrease in hemodynamics, microcircula-tory parameters of the bowel serosa were not significantly affected.

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Troponin release after major non-cardiac surgery: from marker to eventK.H.J.M. Mol, S.E. Hoeks, R.J. Stolker, F. van Lier

Erasmus Medical Center, Rotterdam

IntroductionElevated troponin levels after surgery strongly predict (cardiovascular) mortality within the first year after surgery, however it is not known whether this relationship also applies for major adverse cardiovascular events (MACE). We evaluated the role of troponin release in relation to non-lethal MACE in the first year after surgery.

MethodsThis prospective study included 3537 patients undergoing major non-cardiac surgery in the Erasmus Medical Center be-tween July 2012 and December 2015. Routine high-sensitive troponin T measurement was implemented as standard clinical care from

2012 onwards and measured the first 3 days after surgery. Myocardial injury was de-fined as a rise of troponin above the clinical reference of 14 ng/L. Troponin values were categorized: 0-13,99 (not elevated), 14 -14,99 (minor elevation), 50-149,99 (moderate elevation) and > 150,00 ng/L (major eleva-tion). MACE is the composite endpoint of non-lethal myocardial infarction, angina, coronary revascularization and cerebrovas-cular accidents within 1 year after surgery.

ResultsMyocardial injury after surgery was detected in 1929 patients (54.5%); 3%, 7.5% and 34.7% for minor, moderate and major elevation, respectively. Death within the first year after surgery occurred in 523 (14.8%) of patients (HR 6.1 (95% CI, 4.4 – 8.3) for patients with major troponin release. Of all patients who survived the first year follow-up could be

obtained in 2676 patients. MACE occurred in 4,7% of patients and a stepwise increase was observed in relation to perioperative troponin elevations, with HR 2.1 (95% CI, 1.4 -3.3) for minor, HR 3.1 (95% CI, 1.7 – 5.7) for moderate and HR 18.0 (95% CI, 10.0 – 32.4) for major elevation.

ConclusionPerioperative myocardial injury is related to both increased mortality and increased risk for non-lethal major adverse cardiac events in the first year after surgery. Our data strongly suggest serious hazards for cardiovascular morbidity in patients with myocardial injury after surgery during long-term follow-up.

SESSI E 3 - 10 min

The prevalence of chronic neuropathic pain in survivors of critical illness: an observational pilot studyW.K.M. van Os, M.E. Koster-Brouwer, O.L. Cremer, M. Rijsdijk

University Medical Center Utrecht

IntroductionCritically ill patients who have survived a prolonged intensive care unit (ICU) admission frequently suffer from chronic pain, and concomitantly from poor health-related quality of life. However, the origin of this pain remains unclear. Discriminating between nociceptive or neuropathic char-acteristics of pain, will help understanding underlying pathophysiological mechanisms. This study measured the prevalence of neu-ropathic pain (NeP) characteristics among ICU survivors reporting chronic pain.

MethodsAdults reporting a new-onset chronic pain following an ICU stay of more than 48 hours in 2013-2015 were identified using a standard follow-up questionaire distributed 1 year after hospital discharge. Subsequent-ly, we used the Douleur Neuropathique 4 questions questionnaire to prospectively assess NeP. Additionally, other pain, ICU, and patient characteristics were collected. All participants provided written informed consent.

ResultsIn the present study, 48 patients with chronic pain were included after a median follow up of 35 months. Among these, NeP characteristics were observed in 25 (52% [95%CI: 38-66]) patients. No statisti-cally significant differences were observed

between patients with and without NeP characteristics. However, trend effects were observed suggesting a higher risk of NeP in males and patients with sepsis as their main reason for ICU admission. Also, chronic pain with NeP characteristics was more frequently located in the distal and lower extremities, and was more prevalent in patients reporting chronic pain in multiple sites.

ConclusionThis pilot study suggests that a significant proportion of ICU survivors experience chronic pain that exhibits NeP character-istics. Investigations into possible lesions or diseases of the somatosensory nervous system implied in the pathogenesis of neuropathic pain during critical illnes are warranted.

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The effect of a glucocorticoid containing cardioplegia solution on mortality after cardiac surgery: a historical cohort studyM. Nouwen, S. Rigter, L. Miggelbrink, N. Saouti, P.G. Noordzij

St. Antonius Hospital, Nieuwegein

IntroductionCardiopulmonary bypass triggers systemic inflammation and has been associated with an increased risk of death and major mor-bidity. Glucocorticoid therapy reduces the inflammatory response, but studies on prophylactic intravenous high dose glucocorticoid therapy have not shown an improvement in mortality after cardiac sur-gery. The effect of a glucocorticoid contain-ing cardioplegia solution on postoperative outcome is unknown.

MethodsPatients who had cardiac surgery with cardiopulmonary bypass between Janu-ary 2014 - September 2016 in St. Antonius Hospital were eligible for inclusion. On January 1st 2016 Bleese cardioplegia solution was replaced with St. Thomas cardioplegia solution for all cardiac surgery procedures. Bleese cardioplegia contains 40 mg dexa-methasone per litre, St. Thomas cardiople-gia contains no glucocorticoids. Prophy-lactic intravenous glucocorticoid therapy was not part of local routine anesthesia care. Perioperative data were extracted retrospec-tively from a computerized medical system (Metavision Suite). Primary outcome was hospital mortality. Change point analyses were performed to analyse trends in mortal-ity and risk factors for mortality. Logistic regression analyses were used to determine the effect of type of crystalloid cardioplegia solution on postoperative outcome.

ResultsThe study population consisted of 2848 pa-tients. Baseline characteristics were similar

between groups (not shown). Mortality was 3.9% (85/2188) and 4.5% (30/660) for patients with Bleese and St. Thomas cardioplegia re-spectively (P=0.432). No significant change point was present for mortality during the study period (see figure). After adjustment for age, gender, euroSCORE and blood transfusion, type of cardioplegia solution was not associated with mortality (adjusted OR 1.079 and 95% CI 0.689-1.688 for patients with Bleese cardioplegia; see table).

ConclusionA crystalloid cardioplegia solution contain-ing glucocorticoids is not associated with mortality after cardiac surgery.

Figure. Mortality during the study period

Table. Multivariate logistic regression analysis for type of cardioplegia solution and mortality.

Patient characteristics Adjusted OR (95% CI)

Bleese cardioplegia 1.079 (0.689 – 1.688)

Age 0.997 (9.76 – 1.017)

Male gender 0.815 (0.548 – 1.212)

EuroSCORE 1.365 (1.291 – 1.444)

ECC duration 1.009 (1.007 – 1.011)

RBC transfusion 7.892 (3.687 – 16.895)

ECC extra corporeal circulation; RBC red blood cell

Figure. Mortality during the study period

Table. Multivariate logistic regression analysis for type of cardioplegia solution and mortality.

Patient characteristics Adjusted OR (95% CI)

Bleese cardioplegia 1.079 (0.689 – 1.688)

Age 0.997 (9.76 – 1.017)

Male gender 0.815 (0.548 – 1.212)

EuroSCORE 1.365 (1.291 – 1.444)

ECC duration 1.009 (1.007 – 1.011)

RBC transfusion 7.892 (3.687 – 16.895)

ECC extra corporeal circulation; RBC red blood cell

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SESSI E 3 - 10 min

Functional analysis of the c.38T>G (p.13Leu>Arg) RYR1 variant results this mutation to be listed as causative of Malignant HyperthermiaT. Greven 1,2, J.C.F. Koenen 1, E.J. Kamsteeg 2, M.M.J. Snoeck 1

MH Expertise Centrum Nijmegen: 1 CWZ,2 Radboud University Medical Center

IntroductionIn 1984 an otherwise healthy man died dur-ing an appendectomy because of malignant hyperthermia (MH). His parents, brothers and sisters were investigated for MH suscepti-bility according to the European MH Group protocol. A mutation in the type 1 ryanodine receptor gene (RYR1) was identified. Because this RYR1-variant in the N-terminal region, which might have functional consequences trough conformational changes on theoreti-cal grounds, was not one of the known causal mutations we performed a functional study.

MethodsDiagnostic investigation includes the halothane-caffeine invitro contracture test (IVCT) on a fresh muscle biopsy, CK mea-surement, histopathological investigation and DNA sequention analysis of the RYR1 gene. Muscle samples (quadriceps femo-ris muscle) of 4 MHS and 2 MHN family members were cultured; in differentiated polynucleated myoblasts the free cytosolic calciumconcentration: [Ca2+]i, could be determined using Fura-2 after exposure to halothane.

ResultsSegregation was found between phenotyp-ing and genotyping, respectively MHS individuals in the IVCT with c.38T>G in

RYR1 and MHN without a mutation. The dose dependant increase of [Ca2+]i differs significantly between myoblasts from MHS-diagnosed individuals carrying the c.38T>G mutation compared to those of normal patients whitout overlap beyond 0.44mM halothane (2% vv).

ConclusionBy this study the c.38T>G RYR1 variant fulfils the criteria for causality and because the variant is found in a second unrelated Japanese family it can be put on the EMHG list that contains diagnostic mutations for diagnosing MH susceptibility.

SESSI E 3 - 15 min

Electrical stimulation of the forearm to induce venodilationM. van Lieshout, D.A.M. de Gier, L.T. van Eijk, C. Keijzer-Broeders

Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, Nijmegen

IntroductionIntravenous catheter placement is one of the most common in-hospital procedures. However, the rate of unsuccessful catheter insertion is high, especially in obese, edema-tous or chemotherapy patients. Veinplicity is an electrical stimulation device developed to increase local blood flow to facilitate peripheral cannulation. We investigated whether veinplicity is superior to the use of a conventional tourniquet with regard to venodilation.

MethodsA prospective cross-over study was per-

formed in 12 healthy volunteers. Participants were subjected to 1) the application of a tourniquet for 2 minutes (T) and 2) stimula-tion with Veinplicity on maximum tolerable intensity for 10 minutes (VP), followed by application of a tourniquet for 2 minutes. The order of treatments was randomly as-signed, and the treatments were separated by an interval of at least 20 minutes. The diameter of the vein was measured at the level of the elbow using ultrasound. The exact ultrasound location was marked. Pre- and post treatment ultrasound images were evaluated by an investigator blinded to the study treatment.

ResultsVeinplicity was well tolerated by the par-ticipants (8 males, 4 females, age 28±3.8 years, BMI 22.2±1.6 kg/m2). Both Veinplic-ity and tourniquet significantly increased

vein width (VP from 5.3±2.0 to 7.1±3.7 mm, T from 5.8±2.3 to 6.6±2.2 mm), height (VP from 3.3±1.3 to 4.3±1.6 mm, T from 3.6±1.1 to 4.8±1.4 mm) and cross sectional area (VP from 15±12 to 27±23 mm2, T from 17±11 to 27±17 mm2), p<0.05 for all parameters. There was no correlation between the ap-plied stimulation strength over time and achieved venodilation (Spearman r=0.24, p=0.44). Applying the tourniquet after veinplicity stimulation did not significantly attribute to further venodilation. There was no difference in the venodilation induced by Veinplicity compared with a tourniquet.

ConclusionVeinplicity induces venodilation, but is not superior to the use of a conventional tour-niquet.

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SESSI E 4 - 15 min

The two-faced action of CO2 on the cerebral vasculatureN.H. Sperna Weiland 1,2, J. Hermanides 1, M.W. Hollmann 1, B. Preckel 1, J.J. van Lieshout 2,3, W.J. Stok 2, R.V. Immink 1,2

1 Department of Anaesthesiology, Academic Medical Centre Amsterdam

2 Laboratory for Clinical Cardiovascular Physiology, Academic Medical Centre Amsterdam

3 Department of Internal Medicine, Academic Medical Centre Amsterdam

University of Amsterdam, Amsterdam

IntroductionCerebral autoregulation (CA) maintains cerebral blood flow velocity (CBFV) more or less constant in response to changes in blood pressure (BP).1 Apart from CA, CBFV is positively correlated with changes in end-tidal partial pressure of arterial CO¬2 (PetCO2). Also, in awake subjects, increas-ing PetCO2 impairs CA progressively. The aim of this study was to explore the deterio-

ration of CA during an increment in PetCO2 in anaesthetised patients.

MethodsBoth pre- and intraoperatively, BP, CBFV and PetCO2 were recorded in 15 ASA 1 or 2 patients, aged 58±11 years (mean±SD), weight 75±15 kg and height 172±8 cm. CA was determined during three minutes of hypo-, normo- and hypercapnia. CA was calculated using frequency domain analysis as the CBFV-to-BP phase lead expressed in degrees (°). Intact CA is characterised by a ~50° phase lead and this decreases <30° if CA is impaired.

ResultsPetCO2 was 33±4 vs 36±3, 41±5 vs 40±3 and 50±4 vs 49±4 mmHg during hypo-, normo- and hypercapnia in awake versus anaesthe-tised patients. CBFV increased together with PetCO2 from 33±4 vs 36±3 to 41±5 vs 40±3 to 50±4 vs 49±4 cm·s-1. Phase lead decreases together with PetCO2 from 67±23 vs 51±15 to 37±7 vs 43±8 to 10±9 vs 15±12°. CA efficacy decreases 3.5 [IQR 3.8 to 1.7] vs 3.2 [IQR 3.8 to 0.9]°·mmHg-1 in awake versus anaesthetised patients.

ConclusionIncreasing PetCO2 produces cerebral va-sodilation that increases CBFV on the one hand, but reduces CA efficacy on the other hand. This PetCO2 induced deterioration of CA does not change when anesthetised.

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SESSI E 4 - 15 min

Spinal Morphine for laparoscopic segmental colonic resection (SALMON-trial); a randomized controlled trialM.V. Koning 1,2, A.J.W. Teunissen 2, E. van der Harst 3, L. Ruijgrok 4, R.J. Stolker 1

1 Department of Anesthesiology, Erasmus Medical Center, Rotterdam

2 Department of Anesthesiology, Maasstad Hospital, Rotterdam

3 Department of Surgery, Maasstad Hospital, Rotterdam

4 Department of Pharmacology, Maasstad Hospital, Rotterdam

IntroductionPostoperative pain management after laparoscopic segmental colonic resections remains controversial. We compared two alternative methods of analgesia within an Enhanced Recovery After Surgery (ERAS)-program. The goal of the study was to investigate whether spinal morphine would limit the need for systemic opioids, thereby decreasing the systemic side-effects, and

SESSI E 4 - 15 min

Norepinephrine use contributes to intestinal damage in septic shock patientsQ.L.M. Habes, L. van Ede, J. Gerretsen, M. Kox, P. Pickkers

Radboud University Medical Center, Nijmegen

IntroductionIn septic patients, both systemic inflam-mation and splanchnic hypoperfusion may cause enterocyte damage. Catecholamines may exert additional detrimental effects on mesenteric blood flow, and thereby contribute to this damage, resulting in impairment of gut barrier function and consequent translocation of bacteria/toxins. This may contribute to multiple organ fail-ure and death by sustaining or amplifying the systemic inflammatory response. We investigated which factors contribute to en-terocyte damage in septic patients, and we assessed whether enterocyte damage plays a role in sustaining the systemic inflammatory response.

MethodsBoth pre- and intraoperatively, BP, CBFV and PetCO2 were recorded in 15 ASA 1 or 2 patients, aged 58±11 years (mean±SD), weight 75±15 kg and height 172±8 cm. CA was determined during three minutes of hypo-, normo- and hypercapnia. CA was calculated using frequency domain analysis as the CBFV-to-BP phase lead expressed in degrees (°). Intact CA is characterised by a ~50° phase lead and this decreases <30° if CA is impaired. We studied 129 adult septic shock patients. Blood was obtained at admission and at several days thereafter. Plasma concentrations of I-FABP and the cytokines Tumor Necrosis Factor (TNF)-&#945;, Interferon (IFN)-y, Interleukin (IL)-1&#946;, IL-6, IL-8, IL-1 Receptor Antagonist (RA), and IL-10 were measured. Clinical data (APACHE II-score, creatinine levels, MAP, and norepinephrine dose) were collected from electronic patient files.

ResultsMedian norepinephrine infusion rate was 0.2 µg kg-1 min-1 [0.1-0.5]. Overall 28-day mortal-ity was 31 (24%). I-FABP levels at admission were independently associated with mortal-ity (OR 3.101 [1.138-8.448]). APACHE II-score and an increase in norepinephrine infusion rate between days 1 and 3 were independently associated with AUC I-FABP levels, whereas MAP and creatinine levels were not. No correlations were found between any of the measured cytokines and I-FABP levels. Fur-thermore, high I-FABP levels were not related with the subsequent course of cytokine levels.

ConclusionIn patients with septic shock, norepinephrine use is associated with more enterocyte dam-age. Although enterocyte damage is associ-ated with increased 28-day mortality, it does not appear to play a role in sustaining or am-plifying the systemic inflammatory response.

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enhancing postoperative recovery as com-pared to intravenous opioids.

MethodsA single-center randomized double-blinded controlled trial was performed after ap-proval of an independent ethical committee (NL43488.101.13). All patients who were scheduled for laparoscopic segmental co-lonic resections were considered. Exclusion criteria were patients in whom contra-indi-cations were present for spinal anaesthesia. Furthermore, bariatric, rectal surgery and operations that were converted to open sur-gery were excluded. After written informed consent patients were allocated to a spinal group (S) or a control group (C). S-group

received single shot spinal bupivacaine/mor-phine (12.5 mg/300 mcg). C-group received a placebo and intraoperative piritramide (0.1 mg/kg). Both groups received standardised general anaesthesia and a PCA-pump as postoperative analgesia. All patients were treated according to an ERAS-protocol.

Results56 patients were enrolled. In the S-group patients were earlier “fit for discharge” than those in the C-group (3 (3-4)[1-28] vs 4 (3-5)[2-25] days, p=0.044). Sixteen patients (59%) in the S-group versus 10 patients (34%) in the C-group were “fit for discharge” on the third postoperative day. Furthermore, there was a decrease in opioid-use and lower pain

scores on the first postoperative day in the S-group. There were no differences in ad-verse events (except for more pruritus in the S-group) or time-to-mobilization. S-group seems to be more satisfied, although this was non-significant.

ConclusionThis RCT shows that spinal morphine is an appropriate method of postoperative analgesia in laparoscopic surgery within an ERAS-program. Recovery is faster and less painful in the S-group. However, more pru-ritus was recorded on the first postoperative day. Other studies have confirmed these results, although the data on a faster recov-ery is new.

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R.R.I. van Reij 1

I. Eijkenboom 2

J. Vanoevelen 3

D.M.N. Hoofwijk 4

E.A.J. Joosten 5

N.J. van den Hoogen 6

Genetica en perioperative medicineDeel 3 : genetische screening, nociceptie en pijn in zebravissen

1 AIO, Lab Exp.Anesthesiologie, MUMC+, Maastricht

2 AIO, Lab Klinische Genetica, MUMC+, Maastricht

3 Ass.Prof., Lab Klinische Genetica, MUMC+, Maastricht

4 Anesthesioloog, Anesthesiologie, MUMC+, Maastricht5 Prof. Dr., Exp.Anesthesiologie, MUMC+,

Maastricht6 AIO, Lab Exp.Anesthesiologie, MUMC+,

Maastricht

contactinformatieDept.Anesthesiologie en Pijn Management MUMC+T.a.v. Nynke van den HoogenP. Debyelaan 25PO Box 58006202 AZ MaastrichtT+31 (0) 43 3881034Email [email protected]: geen

onderzoek

Zebravissen en onderzoekDe zebravis (Danio rerio) is een steeds populairder wordend alternatief voor gebruik van traditionele proefdieren in experimenteel preklinisch onder-zoek. Het kleine visje (±4cm) is afkom-stig uit -Zuidoost Azië; India, Pakistan, Bangladesh, Nepal en Myanmar en heeft een voorkeur voor stilstaand zoet water. De zebravis ontwikkeld zich zeer snel, is na 5 dagen in staat om zelfstandig rond te zwemmen en op zoek te gaan naar voedsel. Tijdens de embryonale fase is de zebravis groten-deels doorzichtig.De zebravis is zeer geschikt als proef-dier omdat het een gewerveld organis-me is met een vergelijkbare fysiologie en genetische opbouw als mensen. De zebravissen zijn door hun grootte en snelle voortplanting zeer geschikt voor high-throughput screening van gedrag en in farmacologische studies. Vanwege het feit dat ze doorzichtig zijn tijdens hun ontwikkeling, worden ze veel gebruikt om de ontwikkeling van organen te onderzoeken waarbij eventuele veranderingen gemakkelijk te observeren zijn.Het genoom van de zebravis is volledig bekend en wordt veelvuldig gebruikt in genetische studies om het effect van bepaalde mutaties te bestuderen. Een gedeelte van het genoom van de zebravissen is gedupliceerd wat één op

één vergelijking tussen het humane ge-noom en zebravis genoom soms lastig maakt. Echter, in de meeste gevallen is bekend welke genen vergelijkbaar zijn met de humane genen. Het natuurlijke gedrag van de zebravis is in de laatste jaren goed gekarakteriseerd en dit maakt het mogelijk om degelijk en valide onderzoek te doen [1-5].

Nociceptie en pijn in zebravissen?De reactie op potentieel beschadi-gende stimuli middels gespecialiseerde zenuwuiteinden of nociceptoren in bijvoorbeeld huid en spier en de daardoor activatie van sensorische zenuwbanen (= nociceptie) kan in een zebravis onderzocht worden. Met

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betrekking tot het onderzoek naar pijn, een complex geheel van zowel sensorische als psychologische en componenten [6, 7], is de zebravis veel moeilijker te gebruiken. Het vervolg van dit artikel gaat dan ook over het meten van nociceptie en dus de reactie van de zebravis op nociceptieve signa-len [6, 7]. Om nociceptieve signalen te kunnen waarnemen is er een neurobiologisch systeem nodig die zowel de stimuli kan opvangen, verwerken en module-ren via endogene moleculen. Verschil-lende onderzoeksgroepen hebben aangetoond dat vissen nociceptoren hebben die grotendeels vergelijkbaar zijn met die bij zoogdieren en dat deze ook reageren op thermische, mechanische of chemische stimuli [8-10]. Naast de aanwezigheid van nociceptoren, is tevens aangetoond dat er in vissen nociceptie specifieke sensorische C- en Aδ- vezels aanwezig zijn, welke via neuronale projecties het nociceptieve signaal van de perifere ze-nuwen richting de hersenen stuurt [6, 7]. Daarnaast is in de zebravissen een opioïd systeem aanwezig wat in staat is het nociceptieve signaal te moduleren. Er zijn verschillende homologen van opioïde receptoren aanwezig in de zebravis en het is aangetoond dat mor-fine en andere opiaten de nociceptieve respons kunnen beïnvloeden en een analgetische werking hebben [8, 11-13].

Nociceptie en de zebravis: gedragsanalysesDe methoden om nociceptie te testen in zebravissen kan opgedeeld worden in interne en externe stimuli. Het tes-ten van nociceptie door middel van in-terne stimuli gebeurt meestal door het injecteren van irriterende of inflam-matoire stoffen. De externe stimulus is meestal een grote temperatuurstijging van het water dan wel de toevoeging van irriterende compounds aan het water. Vervolgens wordt het gedrag van de zebravis bestudeerd om te zien of de stimulus een verandering in gedrag opwekt. Het testsysteem (zie Figuur 1) is zo ontworpen dat de vissen van bovenaf gefilmd en geanalyseerd

kunnen worden terwijl de situatie waarin de vissen zich bevinden kan worden aangepast. Bijvoorbeeld, bij externe stimuli kan de temperatuur van de waterstroom worden aangepast en kan in real-time de reactie van de zebravissen gefilmd en geanalyseerd worden. Het gedrag kan op verschil-lende manieren geanalyseerd worden. Er kan gekeken worden naar de zwem-patronen van de zebravis en of die ver-anderen na de stimulus. Daarnaast kan ook het zwemgedrag van de zebravis gekarakteriseerd worden. Hierbij wordt gekeken naar de algehele activi-teit tijdens het meetmoment, alsmede componenten waaruit dit zwemgedrag bestaat (nauwelijks bewegen, heel snel wegzwemmen, gemiddelde beweging of geen beweging). Alle meetmomen-ten tijdens de proef worden achter elkaar gezet en geanalyseerd om te kijken of de zebravis reageert op de stimulus (zie Figuur 2).Daarnaast kan door middel van histo-logische studies bekeken worden of het toevoegen van externe stimuli of irriterende inflammatoire stoffen aan het water veranderingen heeft ver-oorzaakt in de anatomie en fysiologie van het nociceptieve systeem. Indirect kan deze aanpak dus leiden tot het testen van effect van analgetica op

het gedrag. Onderzoek heeft aange-toond dat thermische gevoeligheid of hyperalgesie bij zebravissen gemeten kan worden: als de zebravis de keus heeft tussen zwemmen in water van 28,5oC of 36,5 dan zal de vis meer tijd doorbrengen in het water van 28.5oC. Wanneer vervolgens een opiaat recep-tor (u-receptor) agonist, buprenorphi-ne, wordt toegediend aan het water waarin deze vissen zwemmen dat dan hun temperatuur-voorkeur voor 28,5 oC verdwijnt en ze vervolgens even-veel tijd door brengen in het compar-timent met een temperatuur van 36,5 oC als in het controle-compartiment met een watertemperatuur van 28,5 oC [11, 13-15].

Nociceptie en de zebravis: genetische studiesHet onderzoek naar nociceptie en pijn in de zebravis wordt vaak ge-combineerd met genetische studies. Vanwege hun snelle voortplanting en vele nakomelingen per kruising zijn de vissen ideaal voor screening op aanwezigheid van genetische varian-ten. Er kan op verschillende manieren gekeken worden naar het effect van genetische variatie op de vissen. De start van een genetisch onderzoek kan liggen bij het fenotype (forward

Figuur 1. Schematische weergave van de opstelling die gebruikt wordt om het gedrag van de zebra-vis te bestuderen. De vissen worden individueel verdeeld over een 48-wells plaat en in het apparaat geplaatst. In het apparaat hangt een camera die verbonden is aan een computer die de gegevens in real-time opneemt en analyseert. De water toevoer is flexibel en waardoor er gewisseld kan worden tussen water van 28.5 °C en 36.5 °C om te bestuderen hoe dit het gedrag beïnvloedt. (aangepast van Prober et al., 2008 [19]).

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genetic screening), waarbij je vanuit een waargenomen probleem de onderlig-gende genetische oorzaak zoekt, of bij het genotype (reverse genetic screening), waarbij er een genetische variant in de zebravis geïnduceerd wordt en daarna het (gedrags-)effect wordt geanaly-seerd. Twee van de meest gebruikte snelle, transiënte technieken om via reverse genetic screening genetische variatie te onderzoeken zijn momen-teel de RNA-overexpressie en de mor-folino techniek. Bij RNA overexpressie wordt het mRNA van het eiwit van interesse met de variatie al ingebouwd, geïnjecteerd in het zebravis embryo. Dit is een zeer efficiënte en snelle techniek waarmee snel het effect van de genetische variatie kan waarnemen zonder het eindeloos kruisen van ver-schillende zebravis stammen om het gewenste effect te krijgen. De tweede techniek, de morfolino-techniek, werkt door middel van gebruik van gemodificeerde oligonucleotiden. Deze oligonucleotiden lijken op RNA sequenties en binden specifiek aan het mRNA van het eiwit van interesse. Vervolgens zorgt de gemodificeerde oligonucleotide ervoor dat het betref-fende eiwit niet tot expressie komt en dus niet werkzaam is in die cel. Dit kan worden gebruikt om te onderzoeken

wat de rol van een specifiek eiwit is in een bepaalde reactie [4, 16-18].

Toepassingen en translationeel onderzoekDe vele mogelijkheden van de zebravis gecombineerd met de snelle voort-planting en het feit dat hij doorzichtig is tijdens de ontwikkeling maken de zebravis een zeer interessant proefdier-model voor verschillende onderzoeks-velden waaronder nociceptie en pijn. In het kader van translationeel onder-zoek kan de zebravis een waardevolle stap vormen omdat het de moge-

lijkheid biedt tot snelle, goedkope screening van genetische mutaties en hun effect op nociceptie en pijn. Vervolgens kunnen in korte tijd vele bestaande als wel nieuwe farmaca getoetst worden op hun analgetische werking. Dat er vervolgens gerichte stappen nodig zijn ( bijvoorbeeld preklinische studies in knaagdieren) om terug in de kliniek te komen is lo-gisch. Maar toch zal dit kleine visje een belangrijke bijdrage kunnen gaan le-veren aan het oplossen van zo’n groot vraagstuk als de optimale behandeling van (chronische) postoperatieve pijn.

Figuur 2. Het zebravis experiment is in drie fases te verdelen. Na het plaatsen van de vissen in het apparaat krijgen de dieren 30 minuten om te acclimatiseren aan de opstelling en omstandigheden. Vervolgens wordt vanaf minuut 30 tot 40 een baseline meting gedaan. Na 40 minuten wordt de temperatuur van het water verhoogd en bevinden de vissen zich in de experimentele fase. De activiteit van de vissen gaat significant omhoog bij de start van de experimentele fase maar na verloop van tijd zwakt dit af. De data in de grafiek is weergegeven als gemid-delde ± standard error of the mean (SEM).