anesthesiologie Nederlands tijdschrift voor Wetenschap special volume 21, augustus 20094

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1 Nederlands tijdschrift voor anesthesiologie Wetenschap special volume 21, augustus Dr. M. Klimek, hoofdredacteur Prof. Dr. M.A.E. Marcus, plaatsvervangend hoofdredacteur Officiële uitgave van de Nederlandse Vereniging voor Anesthesiologie Wetenschappelijk onderzoek investeren in talenten S.A. Loer Abstracts Wetenschapsdag 2009 Scientific Misconduct in Anesthesia Research: No Exception to the Rule J.W. van Kleef, J. Loadsman, S. Shafer, A. Dahan Opioïd-geïnduceerde hyperalgesie ontstaat onafhankelijk van opioïdreceptor-activatie E.Y. Sarton

2 Op mijn leeftijd slik je niet zomaar iets tegen de pijn Wil van Brakel, 62 jaar heeft last van lage rugpijn. Zaldiar. De paracetamol plus alle voordelen van paracetamol plus de kracht van tramadol 1,2,3 minimaal risico op orgaanschade 4,5,6,7 bekend, vertrouwd en volledig vergoed 60 plus. Zaldiar dus. paracetamol 325 mg + tramadol 37,5 mg

3 Ernstige, onverwachte bloeding subcutaan, weke delen Tijdig denken aan verworven hemofilie kan een leven redden

4 2 nederlands tijdschrift voor anesthesiologie augustus '09 inhoud Nederlands tijdschrift voor anesthesiologie volume 21 Nummer 4 augustus 2009 Coverbeeld: Shutterstock editorial 5 Wetenschappelijk onderzoek investeren in talenten S.A. Loer abstracts wetenschapsdag o r a l p resentat i o n 6 Effects of high altitude hypoxia and iloprost on right ventricular function in healthy volunteers E. Kortekaas, B. Jaiswal, K. Ruh, G.P. Foster, J.D. Anholm, J.C. de Graaff o r a l p resentat i o n 7 The selective a7nachr agonist GTS-21 attenuates ventilator-induced inflammation and lung injury M. Kox, J.C. Pompe, M. Vaneker, L.M. Heunks, J.G. van der Hoeven, C.W. Hoedemaekers, G.J. Scheffer, P. Pickkers o r a l p resentat i o n 7 Left ventricular ejection fraction assessed by 2D and 3D echocardiography: Does experience matter? F. de Lange, J. Karhausen, B. Phillips-Bute, M. Swaminathan, B. Mackensen o r a l p resentat i o n 8 Cerebral autoregulation is unaltered by sympathetic denervation with stellate ganglionic blockade R.H.A. Passier, R.V. Immink, J. Truijen, J.H. Vranken, M.H. van der Vegt, M.W. Hollmann, J.J. van Lieshout, o r a l p resentat i o n 9 Effect of N-methyl-D-aspartate receptor (NMDA-R) antagonists in a rat model of neuropathic pain M. Swartjes, A. Dahan, A.M. Morariu o r a l p resentat i o n 10 Molecular diagnosis of ryr1 gene mutations causative for susceptibility to malignant hyperthermia and/or central core disease using the MLPA method M.S. Snoeck, J.C.F. Koenen, Y. Aardsen, C. Klaasen p o s t e r d i s c u s s i o n 11 Shock induced stress induces loss of microvascular endothelial Tie2 in the kidney F.M. Wulfert, M. van Meurs, N.F. Kurniati, R. M. Jongman, J.G. Zijlstra, M. M. R. Struys, G. Molema poster discussion 11 Syndecan-4 modulates inflammation in ALI T. Harendza, J. Larmann, U. Maus, F. Echtermeyer, G. Theilmeier 12 Contribution of S(+)-norketamine to S(+)-ketamine effect on cardiac output in a cross-over study in healthy volunteers I.M. Noppers, F.K. Mouton, A.M. Morariu, E. Olofsen, R.A.G. Mooren, E.Y. Sarton, A. Dahan 12 The Advanced Trauma Life Support in severely burned patients is associated with an increase in mechanical ventilation and complication rate F.B. van Dehn, D.P. Mackie, P. Knape, C. Boer 13 Impact of platelet function analysis on decision making in preeclampsia F.H. Tijssen, V.M. Smit-Fun, V.C.M.L Timmer, A. Kroese, M.A.E. Marcus, M.D. Lance 13 Midazolam premedication for children undergoing T&A? J.M.K. van Fessem, A.A. van Maris, R.A.J.M. Willems, P.G.J. ten Koppel, A.J.W. Teunissen, R.J. Stolker 14 Acute pain stress increases phosphorylation of DCLK-long in the rat Edinger-Westphal nucleus but not in the hypothalamic paraventricular nucleus T.P.H. Rouwette, L.T. Kozicz, N.F.M. Olde Loohuis, B. Gaszner, E. Vreugdenhil, G.J. Scheffer, E.W. Roubos, K.C. Vissers, W.J.J.M. Scheenen 15 Does a field block reduce the incidence of postoperative pain, nausea and vomiting in oncologic breast surgery? P.M.L.E. Riezebos, M.M.J. Snoeck, L.J.A. Strobbe 15 Effects of sympathetic arousal and interoceptive awareness on pain in fibromyalgia: a feasibility study D.S. Veldhuijzen, A.J.M. van Wijck, R. Geenen, J.W.G. Jacobs, C.J. Kalkman 16 S(+)-ketamine effect on chronic pain and experimental acute pain in Complex Regional Pain Syndrome type 1 patients M.J. Sigtermans, J. van Cosburgh, A. Dahan 16 Fentanyl induces hyperalgesia in humans and mice E.Y. Sarton, A. Dahan, J. Grefkens, B. Kest, M. Boom, E. van Dorp 17 Paravertebral block for analgesia after major oncologic breast surgery: a comparison of continuous paravertebral block, single shot paravertebral block, and single shot wound infiltration E.A.C. Bouman, H.M.S. Theunissen, A.G. Kessels, M.A.E. Marcus, H.F. Gramke 17 Predicting the time course of sensory block after intrathecal injection of lidocaine M.A. Holtkamp, D.J. Eleveld, A.M. van Oort, S. Schiere 18 Chronic neuropathic pain: structural changes in the superficial dorsal spinal cord R. Deumens, R.J.P. Jaken, M.A.E. Marcus, E.A.J. Joosten 18 Spinal cord stimulation reduces the neuronal metabolism of the superficial dorsal horn (DH) after spinal cord stimulation (SCS) in rats with nerve injury induced pain. (preliminary data) H. Smits, T. Pederzani, J.L.M. Jongen, E.A.J. Joosten, F. Huygen

5 augustus '09 nederlands tijdschrift voor anesthesiologie 3 inhoud 19 Erythropoietin-like peptides - protective role in neuropathic pain? A.M. Morariu, M. Swartjes, L.P.H.J. Aarts, A. Dahan 20 Pulsed radiofrequency treatment for postmastectomy pain A. Lukas, R.G.S.M. Perez 20 Chronic post-surgical pain: Is there a role for epidural anesthesia and analgesia in the prevention? H.M.S. Theunissen, E.A.C. Bouman, M.L. Peters, H.F. Gramke, M. van Kleef, M.A.E. Marcus 21 The inter-examiner reliability of pressure algometry for the region of sacroiliac joint K.M. Szadek, S. Ustymenko, S.A. Loer, W.W.A. Zuurmond, R.S.G.M. Perez 21 Anti-inflammatory treatment for Complex Regional Pain Syndrome type-1 (CRPS-1): a meta-analysis S.G.L. Fischer, R.S.G.M. Perez, S.A. Loer, W.W.A. Zuurmond 22 Role for toll like receptor-4 in ventilatorinduced diaphragm dysfunction in mice W.J.M. Schellekens 22 Measurement of perioperative changes in the pulse pressure variation in spontaneously breathing patients T.A. van Veelen, D.C. Hooijberg, K. Treskes, D.P. Veerman, C. Boer 23 Remifentanil-propofol interaction on spontaneous respiration in healthy volunteers tested under open-loop conditions M.C.A. Boom, E. Olofsen, D. Nieuwenhuijs, L. Teppema, A. Dahan 24 Renal microvascular endothelial activation in a mouse model of hemorrhagic shock: is the neutrophil a key player in organ dysfunction? F.M. Wulfert, M. van Meurs, N.F. Kurniati, R.M. Jongman, J.G. Zijlstra, M.M.R. Struys, G. Molema 24 Evaluation of different blood drawing techniques on the results of platelet function tests F.H. Tijssen, Y.M.C. Henskens, H.M.S. Theunissen, R. van Oerle, K. Hamulyak, H. ten Cate, M.A.E. Marcus, M.D. Lance 25 Perioperative alterations in the stress imprint in human plasma lead to the induction of pro-apoptotic and stress markers in cardiomyocytes K.W.L. van Deutekom, J.R. de Jong, J.W.A. Romijn, H.W.M. Niessen, C. Boer 25 Cardiac Output monitoring in cardiac surgery: invasive versus non-invasive T.A.J. Lohuis, N. Tajaate, N.A.H. Helgers, H.M.S. Theunissen, M.A.E. Marcus, M.D. Lance 26 Thrombomodulins lectin like domain (LeD) alters outcome and inflammation in a murine CLP mouse model T. Harendza, T. Barkhausen, F. Echtermeyer, G. Theilmeier 27 The impact of surgery on nitric oxide and its associated cytokine and amino acid biochemical pathways J.W.H. Hol, D.F. Fekkes, C Heijmas-Antonissen, F. Zijlstra, M. Klimek, R.J. Stolker 28 High prevalence of lifestyle risk factors in the surgical population N.H.A. Lecluse, R.L.O. v.d. Laar, J.P. Hering, C. Boer 28 Prehospital endotracheal intubation does not associate with outcome in patients with severe traumatic brain injury G. Franschman, S.M. Peerdeman, T.M.J.C. Andriessen, S. Greuters, G.N. Jukema, S.A. Loer, C. Boer 29 The effects of implementing a new schedule at the preoperative assessment clinic G.M. Edward, B. Preckel, B.S. Martijn, F.J. Oort, J.C.J.M. De Haes, M.W. Hollmann 29 Pulse transit time during induction by a propofol bolus V. Rezvani, M. Reekers, F. Boer, A. Dahan, J. Vuyk 30 Application of microarray-based gene expression technology to malignant hyperthermia M.S. Snoeck, J.C.F. Koenen, E. Sterrenburg, S. van der Maarel opinion 33 Scientific misconduct in anesthesia research: no exception to the rule J.W. van Kleef, J. Loadsman, S. Shafer, A. Dahan Young Investigators Grant Opioïd-geïnduceerde hyperalgesie ontstaat onafhankelijk van opioïdreceptor-activatie E.Y. Sarton

6 Advertentie Het orthopediecentrum van de Sint Maartenskliniek telt ruim 400 medewerkers. De orthopeden, anesthe sio logen en radiologen werken integraal met elkaar samen aan de diagnose en behandeling van onze patiën ten. De formatie van de staf anesthesiologie telt 10,85 fte. Om kwaliteitszorg te kunnen bieden met het best haal bare resultaat voor de patiënt is een bewuste keus gemaakt voor een differentiatie in aandachtsgebieden. Het ziekenhuis heeft een NEN-ISO certificering voor onder meer bloedmanagement, pijnbestrijding en neuromodulatie. Verbetercycli en research zijn een integraal onderdeel van onze zorgactiviteiten. Steeds meer patiënten vinden hun weg naar de Sint Maartenskliniek. Wij huldigen de stelling dat je het beste leert door anderen te leren en hebben derhalve plaats voor een Fellow anesthesiologie m/v De functie U werkt als anesthesioloog en krijgt de kans zich verder te bekwamen op een aantal van de bovengenoemde terreinen. Het fellowship is vooral gericht op het verwerven van expertise op het gebied van de locoregionale anesthesietechnieken, met name de (echogeleide) perifere zenuwblokkades. Van de fellow wordt participatie in lopend wetenschappelijk onder zoek verwacht. Deelname aan een internationale cursus en bezoek aan regionale anesthesiecongressen maken deel uit van het fellowship. Wij vragen Jonge, ambitieuze en enthousiaste anesthesiologen die hun vak goed beheersen en zich graag willen bekwamen in de locoregionale anesthesie. U onderschrijft onze doelstellingen: tevreden patiënten, veilige en efficiënte zorg. U bent een medewerker die verantwoordelijkheid neemt en u communiceert vlot op verschillende niveaus. Wij bieden Een prachtige functie, waarin u zich kunt ontwikkelen in een deelgebied van de anesthesiologie. Deze functie biedt jonge collega s het fundament voor een mooie carrière in of buiten de Sint Maartenskliniek. De Sint Maartenskliniek stuurt op kwaliteit, service en snelle doorstroomtijd en richt zich op prestaties en groei van de medewerkers en de organisatie. Arbeidsvoorwaarden conform de eigen AMS+-regeling inclusief budget voor cursus- en congresbezoek, dienstverband van één jaar. Informatie en sollicitatie Voor nadere informatie kunt u contact opnemen met Dr. R. Stienstra, medisch hoofd anesthesiologie, telefoon (024) Uw schriftelijke sollicitatie kunt u vóór 5 oktober a.s. richten aan de dienst Personeel & Organisatie, t.a.v. drs. P. de Booys, senioradviseur P&O, Postbus 9011, 6500 GM Nijmegen, onder vermelding van vacaturenummer 93/2009. Solliciteren per kan ook: werken@maartenskliniek.nl. Acquisitie naar aanleiding van deze advertentie wordt niet op prijs gesteld. Sterk in beweging

7 augustus '09 nederlands tijdschrift voor anesthesiologie 5 colofon 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 Kernredacteuren: Prof. Dr. L. Aarts, Dr. C. Boer, Prof. Dr. A. Dahan, Dr. H. van Dongen, Prof. Dr. S. de Hert, Dr. M. Klimek, Prof. Dr. J. Knape, Prof. Dr. M.A.E. Marcus, Prof. Dr. G. Scheffer. Ondersteunend redacteuren: Drs. M. van der Beek, Drs. E. Bouman, Dr. P. Bruins, Drs. G. Filippini, Dr. D. Gommers, Prof. Dr. M. Hollmann, Dr. W. Klei, Dr. A. Koopman, Prof. Dr. S. Loer, Drs. S. Schiere, Dr. R.J. Stolker, Dr. B. in het Veld, Dr. K. Vissers, Drs. E. Wiewel. Secretaresse: mw. W. van Engelshoven Voor informatie over adverteren en het reserveren van advertentieruimte in het Nederlands Tijdschrift voor Anesthesiologie: Mw W. van Engelshoven ntva@mumc.nl REDACTIE-ADRES Nederlands Tijdschrift voor Anesthesiologie, mw. W. van Engelshoven, Academisch Ziekenhuis Maastricht, Afdeling Anesthesiologie, Postbus 5800, 6202 AZ Maastricht; ntva@mumc.nl internet: INZENDEN VAN KOPIJ Richtlijnen voor het inzenden van kopij vindt u op of kunt u opvragen bij de redactie of de uitgever. 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, tel , fax , nva@anesthesiologie.nl PRODUCTIE Bladcoördinatie: Drs. Thomas Eldering ( ) Ontwerp: Dimitry de Bruin Eindredactie: Monique de Mijttenaere AUTEURSRECHT EN AANSPRAKELIJKHEID De Stichting tot Beheer van het Nederlands Tijdschrift voor Anesthesiologie 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 foto kopieën, opnamen of enige andere manier, zonder voorafgaande schriftelijke toestemming. Wetenschap kan worden beschreven als geordende kennis van de werkelijkheid. Deze kennis wordt verworven door systematisch wetenschappelijk onderzoek met behulp van specifieke methodes zoals gestructureerde observatie of zorgvuldig opgezette experimenten. Uiteindelijk is het doel om met precisie en objectiviteit de lacunes in onze kennis op te vullen en onze dagelijkse praktijkvoering wetenschappelijk te onderbouwen. De anesthesiologie en perioperatieve geneeskunde bieden zeer interessante perspectieven voor wetenschappelijk onderzoek. Anesthesiologen observeren en beïnvloeden een groot aantal fysiologische - meestal vitale - lichaamsfuncties. Er zijn echter nog talloze lacunes op het gebied van de perioperatieve geneeskunde; lange termijn effecten van een algehele anesthesie zijn nog weinig onderzocht. Om wetenschappelijk onderzoek te realiseren hebben we ambitieuze talenten nodig, die de academische uitdaging zoeken. Deze moeten we actief zoeken en faciliteren. Helaas is ons specialisme tijdens de opleiding tot basisarts weinig zichtbaar, vooral voor jonge talenten. Sommige van hen realiseren te laat of helemaal niet dat anesthesiologie een veelzijdig en interessant vak is. Naast het aantrekken van talenten speelt het faciliteren een belangrijke rol. De Young Investigator Grant 2009 die jaarlijks door de Nederlandse Vereniging voor Anesthesiologie aan jonge gepromoveerde onderzoekers uitgereikt wordt is een voorbeeld hiervan. In essentie gaat het erom deze talenten een duidelijk academische perspectief te bieden, hier hebben we nog huiswerk te doen. Een cruciaal onderdeel van wetenschappelijk activiteit is het openbaar maken van onze onderzoeksresultaten voor anderen, bijvoorbeeld in de vorm van een editorial Prof. dr. S.A. Loer Voorzitter commissie Wetenschap Afdeling Anesthesiologie VU Medisch Centrum Amsterdam s.loer@vumc.nl Wetenschappelijk onderzoek Investeren in talenten wetenschappelijke presentatie of publicatie in een wetenschappelijk tijdschrift. Zonder openbaarheid heeft wetenschappelijk onderzoek geen toegevoegde waarde voor collegae, de maatschappij, en vooral voor onze patiënten. Als landelijk platform heeft de Nederlandse Vereniging voor Anesthesiologie dit jaar voor de zesde keer de wetenschapsdag georganiseerd. Deze dag is bedoeld om onderzoekers en alle geïnteresseerden de mogelijkheid te geven onderzoeksresultaten aan elkaar te presenteren en te bediscussiëren. Het is goed om een stijgende lijn in de kwaliteit van de ingezonden abstracts te zien. Het is ook goed dat meer en meer collegae belangstelling tonen voor wetenschappelijk onderzoek binnen de anesthesiologie. De redactie van het Nederlands Tijdschrift voor Anesthesiologie heeft daarom besloten in deze editie de abstracts van de Wetenschapsdag van de Nederlandse Vereniging voor Anesthesiologie af te drukken om u een overzicht van het brede spectrum aan actuele onderwerpen te bieden. In deze editie hebben we ook een artikel over wetenschapsfraude opgenomen. Hierin worden voorbeelden beschreven van het zondigen tegen precisie en objectiviteit door het manipuleren of zelfs verzinnen van data. Van Kleef et al. maken duidelijk dat wetenschapsfraude negatieve consequenties voor het vak, de scientific community, de onderzoeker maar vooral ook voor onze patiënten kan hebben. Het is een uitdaging om de aantrekkelijkheid en zichtbaarheid van ons vak zo groot mogelijk te maken. Hierdoor kunnen wij de competitie aan met andere specialismen voor het aantrekken van jonge talenten voor anesthesiologisch wetenschappelijk onderzoek. Ik wens u veel plezier met het lezen van deze editie van het NTvA.

8 6 nederlands tijdschrift voor anesthesiologie augustus '09 abstracts oral presentation Effects of high altitude hypoxia and iloprost on right ventricular function in healthy volunteers E. Kortekaas 1 B. Jaiswal 2 K. Ruh 2 G.P. Foster 3 J.D. Anholm 3 J.C. de Graaff 1 1 Universitair Medisch Centrum Utrecht, Utrecht, the Netherlands 2 Loma Linda University, Loma Linda, USA 3 VA Loma Linda Healthcare System, Loma Linda, USA Ascent to high altitude (HA) reduces exercise capacity due to the fall in arterial oxygen pressure and possibly impaired ventricular function. Left ventricular function is normal or minimally altered at HA. Less is known about the effects of prolonged hypoxia on right ventricular (RV) function. Hypoxic pulmonary vasoconstriction (HPV) at HA may contribute to altered RV function. If HPV contributes to RV dysfunction, then inhaled iloprost, a prostacyclin analogue used in the treatment of pulmonary hypertension, may improve RV function. Objective To determine the effects of altitude hypoxia and iloprost on RV systolic and diastolic function in healthy volunteers. A randomized, double blind, cross-over trial of 12 healthy volunteers who participated in the Medex 2008 Expedition to Dhaulagiri, Nepal. Transthoracic echocardiography was performed after placebo and inhaled iloprost (5 microgram), at sea level (SL) and after a 14 day trek to HA at 5050m. Systolic function was assessed by Tricuspid Annular Plane Systolic Excursion (TAPSE). Diastolic function was assessed by tricuspid inflow (TI) E and A wave velocities and tissue Doppler imaging (TDI) of RV free wall of the tricuspid annulus. Additional measurements of SpO2, mean arterial pressure (MAP) and heart rate (HR) were recorded. Measurements were analyzed by paired sample t-test. Caption 1. Saturation and TAPSE were significantly decreased at HA compared with SL. Inhalation of iloprost did not change significantly either of these measurements. TI peak velocities were significantly lower at HA than at SL after placebo, however we did not observe a significant difference after inhalation of iloprost. Caption 2. Research at 5050m altitude A decrease in TAPSE and TI peak velo cities suggests that RV systolic and diastolic function is impaired after a prolonged stay at HA. This is probably caused by hypoxic pulmonary vasoconstriction. However, inhalation of a single dose of iloprost did not reverse these changes in RV function.

9 augustus '09 nederlands tijdschrift voor anesthesiologie 7 oral presentations oral presentation The selective a7nachr agonist GTS-21 attenuates ventilator-induced inflammation and lung injury M. Kox J.C. Pompe M. Vaneker L.M. Heunks J.G. van der Hoeven C.W. Hoedemaekers G.J. Scheffer P. Pickkers Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands Mechanical ventilation (MV) induces an inflammatory response that contributes to lung injury. The efferent vagus nerve can limit the inflammatory response via the α7 nicotinic acetylcholine receptor (α7nachr), the so-called cholinergic antiinflammatory pathway. The aim of this study was to evaluate the effect of the selective α7nachr agonist GTS-21 on inflammation and lung injury induced by MV using clinically relevant ventilator settings. C57BL6 mice (n=40) were i.p. injected with 8 mg/kg GTS-21 or placebo following mechanical ventilation for 4 hours (tidal volume 8 ml/kg; PEEP 1.5 cm H2O; FiO2 0.45). Unventilated mice were used as controls. Arterial blood gases were obtained at the end of the experiment and TNF-α, IL-6, IL-1β, KC and IL-10 were determined in plasma and lung homogenates. Lung TNF-α and IL-10 mrna expression was measured in lung homogenates using quantitative PCR. In GTS-21-treated mice, the alveolar-arterial (A-a) gradient after MV was significantly reduced compared to placebo (18.7± 0.8 vs ± 0.6 kpa; p=0.04). MV resulted in an increase of all cytokines in plasma and lung compared to control mice. TNF-αwas significantly lower in plasma of GTS-21- treated animals compared to placebo (196.2±50.8 vs ±31.9 pg/ml; p=0.04). Similarly, in lung homogenates a distinct trend was observed towards lower TNF-α levels in GTS-21-treated mice (53.9 ± 12.5 vs ± 5.6 pg/mg protein; p=0.06). IL-10 levels were unaffected by GTS-21. MV strongly increased TNF-α mrna expression in lungs of placebo animals (21-fold compared to controls), this was significantly lower in GTS-21-treated mice (12-fold compared to controls; p=0.02). IL-10 mrna expression was similar in GTS-21-treated and placebo animals. GTS-21 inhibits pro- but not anti-inflammatory cytokine production induced by MV. The reduced A-a gradient in GTS-21- treated animals indicates attenuation of lung injury. The cholinergic anti-inflammatory pathway may represent new treatment options for MV-induced lung injury. oral presentation Left ventricular ejection fraction assessed by 2D and 3D echocardiography: Does experience matter? F. de Lange J. Karhausen B. Phillips-Bute M. Swaminathan B. Mackensen Duke University Medical Center, DURHAM, USA The perioperative assessment of ejection fraction (EF) is an important tool to describe global LV function by visually categorizing EF into six clinically distinct ranges. Three-dimensional TEE (3D-TEE) however offers a quantitative assessment of EF. Although higher levels of experience may yield clinically acceptable reliability regardless of the approach, this has not been studied yet. Therefore, we evaluated the intra-observer reliability and the interobserver agreement of 2D and 3D-TEE assessments of EF, each performed by a novice and experienced echocardiographer. After IRB approval, 3D full volume and standard 2D-TEE loops assessing LV function from 50 patients undergoing cardiac surgery were assessed twice offline by a novice and an experienced echocardiographer. 2D-TEE EF was visually estimated based on six ordinal categories (<15%, 15-25%, 25-35%, 35-45%, 45-55%, >55%). Using available built-in software, 3D-TEE EF was quantified numerically. On these data, Spearman and Pearson correlation and Bland-Altman analyses were performed. Intra-observer reliability was high for both observers for the 2D (r=0.87 and r=0.90) and 3D assessment (r=0.93 and r=0.91). Inter-observer correlation for 2D and 3D assessment was r=0.70 and r=0.78 respectively. Bland-Altman analysis of the 2D-TEE assessments revealed a directional observer bias in that the experienced observer tended to rate the EF higher than the novice by almost one category (Figure A). This difference gets larger as the EF values increase. For the 3D assessment

10 8 nederlands tijdschrift voor anesthesiologie augustus '09 abstracts 2009 Bland-Altman analysis revealed no directional observer bias (Figure B). Novice and experienced observers can reproducibly determine EF with either method. There was reasonable correlation between observers in both ratings. However, the 2D-TEE assessment revealed an observer bias towards the experienced observer rating the LVEF higher. This information suggests that assessment based on 3D-TEE data may offer a more reliable quantification, especially for less experienced users. Figure A Figure B oral presentation Cerebral autoregulation is unaltered by sympathetic denervation with stellate ganglionic blockade R.H.A. Passier 1 R.V. Immink 1 J. Truijen 1 J.H. Vranken 2 M.H. van der Vegt 3 M.W. Hollmann 1 J.J. van Lieshout 1 1 AMC, Amsterdam, the Netherlands 2 Medisch Centrum Alkmaar, Alkmaar, the Netherlands 3 Rode Kruis Ziekenhuis, Beverwijk, the Netherlands Cerebral autoregulation (CA) is a complex of fast and slow regulatory mechanisms that maintain a constant cerebral blood flow (CBF) during changes in mean arterial pressure (MAP). Cerebral arteries are innervated by sympathetic fibers but whether sympathetic activity affects the CA in humans is debated. We questioned whether CA is modulated by an increase in sympathetic activity elicited by postural stress in subjects with a sympathetic denervated cerebral hemisphere by unilateral superior stellate ganglion blockade (SGB). In seven patients treated with a SGB for their chronic pain complaints, non-invasive beat-to-beat finger blood pressure (Finometer), middle cerebral artery blood velocity (MCA Vmean; transcranial Doppler) and frontal cerebral oxygenation (FCO; near infrared spectroscopy) were monitored bilaterally in the supine and upright position. Slow acting regulatory mechanisms of CA were quantified by analyzing the difference in MCA Vmean during different steady state levels of MAP at brain level in the supine and upright position. Fast acting regulatory mechanisms of CA were quantified by analyzing the MCA Vmean to MAP phase lead by Fast Fourier Transform during 0.1 Hz spontaneous oscillations in MAP in the supine and upright position. During SGB, tilting decreased MAP at brain level from 87±5 to 78±8mmHg (mean±sem; p<0.05). Phase lead decreased from 48±8º to 40±8º (blocked) and from 47±8º to 40±7º (contra-lateral; all p=ns). The postural decrease in MCA Vmean was 9.2±9.1% vs. 9.9±7.6% and cerebral oxygenation 2.8±2.3% vs. 2.4±2.3% in the blocked and contra-lateral hemisphere respectively (all p=ns). In patients with one sympathetic blocked cerebral hemisphere by GSB, an increase of systemic activity by tilting does not alter MCA Vmean or FCO. Assuming GSB causes ipsilateral cerebral sympathetic denervation implies the sympathetic nervous system is not a significant contributor to the regulatory mechanisms of CA analyzed in this study.

11 augustus '09 nederlands tijdschrift voor anesthesiologie 9 oral presentations oral presentation Effect of N-methyl-D-aspartate receptor(nmda-r) antagonists in a rat model of neuropathic pain M. Swartjes A. Dahan A.M. Morariu LUMC, Leiden, the Netherlands The important role of NMDA-R in the development and maintenance of chronic pain states has been well documented in the scientific literature. NMDA-R antagonists have shown efficacy in preclinical models as well as in patients with neuropathic pain (NP). A large-scale clinical use of NMDA-R antagonists is limited due to unacceptable side effects (hallucinations, sedation, ataxia) of currently available compounds of this class (Ketamine). More recently, a new compound Traxoprodil has been described as a potent, selective NR2B (subunit of NMDA-R) antagonist with proved neuroprotective effects in both animal models of brain ischemia and patients with traumatic brain injury. This study aims to investigate the therapeutic value of Traxoprodil in a rat model of NP (Spared Nerve Injury - SNI model) as compared to Ketamine. The SNI model is demonstrated to be robust and give prolonged neuropathic pain states (>90 days) with pain-behavior modifications (paw inversion, allodynia, Figure 1 hyperalgesia). The drugs were titrated to a dose that gave significant analgesia with tolerable side effects (Ketamine i.v. 3 mg/ kg/hour, Traxoprodil 20 mg/kg/hour for 3hours, 5 consecutive days). The response to tactile/cold allodynia and thermal/ mechanical hyperalgesia was assessed. Side effects were scored and registered. Both NMDA-R antagonists significantly reduced tactile allodynia in rats with neuropathic pain. However, no effects were observed on heat/mechanical hypersensitivity. Ketamine relieved tactile allodynia for 24±6 POD, Traxoprodil for 30±1POD (Figure 1). While Ketamine treatment was accompanied by important side effects (psychotic behavior-locomotor hyperactivity, head waving, overflow incontinence), there was no evidence of any side effects during Traxoprodil treatment. NMDA-R antagonists prove to be effective therapeutic drugs against mechanical allodynia, in this model of neuropathic pain. Traxoprodil exhibited a superior therapeutic index for efficacy versus psychotomimetic side effects.

12 10 nederlands tijdschrift voor anesthesiologie augustus '09 abstracts 2009 o r a l p r e s e n tat i o n Molecular diagnosis of RYR1 gene mutations causative for susceptibility to malignant hyperthermia and/or central core disease using the MLPA method M.S. Snoeck J.C.F. Koenen Y. Aardsen C. Klaasen Canisius-Wilhelmina Ziekenhuis, Nijmegen, the Netherlands In 2002, the multiplex ligation-dependent probe amplification (MLPA) technique was introduced [1]. MLPA is basically a method to make a nucleic acid sample suitable for a multiplex PCR reaction in which up to 45 specific sequences are amplified simultaneous with the use of only one pair of PCR primers. The aim of this study was to test the MLPA method on control DNA samples from 24 individuals who are members of IVCTtested European MH families in which a causative mutation has been detected by using currently available methods and on samples from individuals that have been tested in Nijmegen by the IVCT from 2006 untill MRC-Holland composed an improved kit of 2 mixes (salsa MLPA KIT P281 / P282 TM), containing 33 RYR1 mutations. 3 of the 29 EMHG-causative mutations [2] could not be incorporated because of technical problems; 7 frequently occurring mutations made up the total of 33. Advertentie 23 mutations could be confirmed by MLPA, 1 could not be detected (G7361A); for 9 mutations control DNA had been lacking. In 35 MHS tested individuals from 12 families, 6 mutations were detected without discordance. In 6 MHE tested individuals (5 families) no mutations have been detected. In an MHN tested mother from an index patient we found the A7025G mutation that we had detected in the index! The method is easy to handle, fast, cheap, reproducible and as the assay only requires commonly used technology, it can easily be implemented in a diagnostic MH laboratory for genetic screening [3]. references 1. J.P. Schouten et al, 2002, Nucleic Acids Res.; 30, e A. Urwyler et al, 2001, Br J Anaesth.; 86: TSCI is gevestigd in Amersfoort en is een toonaangevend medisch bedrijf in de ontwikkeling en verkoop van Patient Temperature Management (PTM) produkten. Deze produkten zijn Mistral-Air (patiënt verwarming via lucht), Fluido/Fluido AirGuard Systeem (bloed- en vloeistof verwarming) en ThermoFlect (passieve verwarming). TSCI distribueert deze produkten in grote delen van de wereld. TSCI werkt conform (internationale) standaarden/normen/procedures en is ISO gecertificeerd. Wegens groei zoeken wij een: International Clinical Sales Representative De functie: U begeleidt en traint (nieuwe) gebruikers van onze producten, in en buiten Europa, en maakt ze enthousiast voor het gebruik van onze producten bij de handhaving van Patient Temperature Management. U bouwt goede relaties op met eindgebruikers, Key Opinion Leaders en onze distributeurs. Voor onze distributeurs bent u het aanspreekpunt en geeft u training aan de lokale vertegenwoordigers. Gevraagd: U bent een ervaren anesthesie verpleegkundige of assistent met diploma NZR of gespecialiseerde SEH; ICU verpleegkundige. U heeft uw eerste commerciële ervaring opgedaan in de medical device of pharmaceutische industrie, of u heeft duidelijk aanwezige commerciële talenten die u in deze functie verder wilt ontwikkelen. Goede beheersing van Nederlands en Engels in woord en geschrift; andere talen zijn een pré. Tevens kunt u werken met MS Office. U beschikt over sterke presentatie- en communicatieve vaardigheden. U bent bereidt veelvuldig internationaal te reizen. Geboden: Een succesvolle, innovatieve onderneming. Het bedrijf heeft focus op groei en financiële stabiliteit. De geschikte kandidaat wacht een goed salaris met resultaat afhankelijke incentives en een auto van de zaak. Bent u geïnteresserd stuur een sollicitatiebrief met c.v. binnen 14 dagen naar: The Surgical Company International B.V. t.a.v. Mevrouw E. Leenders Postbus 2582, 3800 GC AMERSFOORT Of per naar Leenders.Ellie@surgcomp.com Acquisitie n.a.v. deze advertentie wordt niet op prijs gesteld. Onderdeel The Surgical Company Group te Amersfoort

13 augustus '09 nederlands tijdschrift voor anesthesiologie 11 poster discussions poster discussion Shock induced stress induces loss of microvascular endothelial Tie2 in the kidney F.M. Wulfert M. van Meurs N.F. Kurniati R. M. Jongman J.G. Zijlstra M. M. R. Struys G. Molema UMCG, Groningen, the Netherlands Acute kidney injury after shock states is a complication of hemorrhagic and septic shock. Both hemorrhagic shock and endotoxaemia induce a pronounced vascular activation in the kidney which coincides with albuminuria. We hypothesized that changes in Tie2, a vascular restricted endothelium receptor tyrosine kinase shown to control microvascular integrity and endothelial inflammation, underlie this loss of glomerular barrier function. Method For induction of HS, male C57Bl/6 anesthetized mice were subjected to controlled HS with a MAP of 30 mmhg during 90 minutes followed by resuscitation with 6% HES. For the induction of endothoxaemia, mice were injected(i.p.) with LPS. After 4, 8, or 24 hours post volume resuscitation or LPS injection mice were sacrificed under isoflurane. In selected animals, neutrophil depletion was established by intraperitoneal injection of anti-nimp antibody 24 hour prior to HS or endothoxaemia induction. mrna expression of Tie2 and E-selectin was measured in kidney by real time RT-PCR. Protein expression of Tie2, E-selectin, and CD45 was measured by immunohistochemistry and ELISA. mrna and protein expression was compared to expression in non-treated counterparts. Micro-albuminuria, as a measure of glomerular barrier function, was measured in mouse urine using a commercial available kit. In mice subjected to hemorrhagic and septic shock, Tie2 mrna and protein were rapidly, and temporarily, lost from the renal microvasculature, and normalized after 24 hours. In parallel to the loss of Tie2 in vivo, an overt influx of neutrophils in the glomerular compartment which coincides with proteinuria, was seen. While neutrophil depletion abolished proteinuria (figure A), Tie-2 was not rescued (figure B). The observed rapid and temporary loss of Tie2 in reaction to hemorrhagic shock and LPS mediated endotoxaemia could not be directly related to the occurrence of proteinuria, and therewith to diminished glomerular barrier function. poster discussion Syndecan-4 modulates inflammation in ALI T. Harendza 1 J. Larmann 1 U. Maus 2 F. Echtermeyer 2 G. Theilmeier 1 Medizinische Hochschule Hannover, Hannover, Germany 1 Department of Anaesthesiology and Intensive Care Medicine, Experimental Anaesthesiology, Hannover Medical School, Germany 2 Department of Pneumology; Laboratory for Experimental Lung Research, Hannover Medical School, Germany The lethality of acute pulmonary inflammation remains high because the pathophysiology is incompletely understood. Intratracheal instillation of lipopolysaccharide (LPS) leads to a 40-fold increased expression of Syndecan-4 (Syn4) in macrophages and Syn4 deficiency causes excess mortality in endotoxic shock. We examined this molecules role in LPS-induced ALI in Syn4-deficient (Syn4-/-) and wild-type mice (WT). LPS was intratracheally instilled in isoflurane (in air) anaesthetized Syn4-/--and WT-mice. After 24h arterial blood gas analysis and BALF were performed. Lungs were either snap frozen and homogenized for rtpcrs or kryo-embedded for immunehistochemical evaluation. Transendothelial migratory capacity of bone marrow derived PMNs was examined in a transmigration assay. Pulmonary LPS instillation in Syn4-/-- mice led to lower arterial po2 (107.2±27 vs.142±15.8mmhg, n=8, p<0.05) and aggravated lactic acidosis (9.06±3.69 vs. 6.33±1.93, n=8). IL-6 and TNFα expression was elevated 1.4- and 8-fold (n=8) in Syn4-/- lungs. Whilst there were no intra-alveolar differences between both groups, Syn4-/--lungs had 2-fold more PMNs (124.7±15.4 vs. 59.6±11;p<0.05). Macrophage content of BALF increased 1.6-fold, while monocyte counts in lung tissue were 3-fold higher in Syn4-/- (9±2.2 vs. 2.9±0.9(WT); p<0.05). rtpcr demonstrated a 52% reduced ICAM-1 expression. Transmigratory capability of Syn4-/--PMNs through activated endothelial cells was less than 50% of WT-PMNs. LPS instillation in Syn4-/- leads to pulmonary accumulation of leukocytes and cytokines. The discrepancy between increased leukocyte recruitment into the lung and reduced leukocyte transmigration to the alveoli suggests a potential role of Syn4 in endothelial transmigration processes. Syn-4 could be a therapeutic target in ALI.

14 12 nederlands tijdschrift voor anesthesiologie augustus '09 abstracts 2009 Contribution of S(+)-norketamine to S(+)-ketamine effect on cardiac output in a cross-over study in healthy volunteers I.M. Noppers F.K. Mouton A.M. Morariu E. Olofsen R.A.G. Mooren E.Y. Sarton A. Dahan LUMC, Leiden, the Netherlands S(+)-ketamine has a stimulating effect on the cardiac output due to its sympathicomimetic properties. S(+)-ketamine is metabolized in the liver into S(+)-norketamine which is considered an active metabolite. The contributing effect of S(+)-norketamine on the cardiac output is the topic of the current study. This prospective randomized cross-over placebo-controlled study was conducted in healthy male volunteers. To study the effects of S(+)-norketamine, rifampicin was used to induce metabolic activity (via CYP3A4) within the liver. Subjects were tested twice, after a 5 day rifampicin pretreatment and after a 5 day placebo pretreatment (pre-treatment was randomised). On both occasions S(+)-ketamine was administered intravenously for 2 hours at a rate of 20 mg.70kg-1.h-1 During the infusion and 3 hours thereafter, cardiac output was measured using the FloTrac sensor connected to an arterial line and a Vigileo monitor. At regular intervals arterial blood was sampled to measure S(+)- ketamine and S(+)-norketamine plasma concentrations. S(+)-ketamine plasma concentrations were similar after placebo and rifampicin pretreatment. However, S(+)-norketamine concentrations were significantly reduced (by > 50%) after rifampicin pre-treatment. Cardiac output increased rapidly after the start of the S(+)-ketamine infusion. The increase in cardiac output was 20-30% larger after rifampicin pre-treatment. The data show that during S(+)-ketamine infusion, a reduction in S(+)-norketamine concentration (but similar S(+)-ketamine concentrations) causes a larger increase in cardiac output. This indicates that S(+)-norketamine has a reverse effect on cardiac output compared to S(+)-ketamine. Possibly, S(+)-norketamine has symathicoinhibitory properties. The Advanced Trauma Life Support in severely burned patients is associated with an increase in mechanical ventilation and complication rate F.B. van Dehn 1 D.P. Mackie 2 P. Knape 2 C. Boer 1 1 VU Medical Center, Amsterdam, the Netherlands 2 Red Cross Hospital, Beverwijk, the Netherlands The introduction of Advanced Trauma Life Support (ATLS) in severely burned patients aimed for improved care and a reduction in morbidity and mortality in this specific patient population. We investigated whether the introduction of ATLS indeed improved clinical care and outcome in severely burned patients. The medical records of 258 consecutive patients with burns of >30% total body surface area (TBSA), who were admitted to the burn centre from January 1987 to December 2006 were retrospectively analyzed and included in a database. Patients were divided into two groups, based on admission date: 1) from 1987 to 1996 (n=135) and 2) from 1997 to 2006 (n=123). Data were analyzed using Chi-square, ANOVA or regression analysis. Both groups did not differ in baseline values including sex, age, gender, weight at admission, facial burns, the %TBSA and the incidence of inhalation injury. However, the relative number of mechanically ventilated patients at day 0 post-burn doubled from 38% to 76% (P<0.001). Moreover, the increase in mechanical ventilation in the post-atls group was associated with an increase in mortality (9 vs.17 casualties in group 1 and 2; P=0.05), the incidence of respiratory complications (2 vs.17 patients; P=0.01) and the need for inotropic support (4 vs.56 patients; P=0.04). A closer evaluation of the outcome in ventilated patients versus spontaneous breathing victims re-

15 augustus '09 nederlands tijdschrift voor anesthesiologie 13 poster walk around vealed that ventilation was associated with an increased fluid balance on day3 and 7 (both P<0.05) and an increase in patients with sepsis and respiratory complications. This study shows an apparent increase in mechanically ventilated burn patients after the introduction of ATLS in The introduction of ATLS in this specific patient population did associate with an increased incidence of complications and mortality. These results warrant a re-evaluation of ATLS as standard care in severely burned victims. Impact of platelet function analysis on decision making in preeclampsia F.H. Tijssen V.M. Smit-Fun V.C.M.L Timmer A. Kroese M.A.E. Marcus M.D. Lance MUMC+, Maastricht, the Netherlands Preeclampsia complicates about 1-2% of all pregnancies. In 10-50% thrombocythopenia occurs. Data on platelet function is rare. This information can be valuable in decision making in respect to choice of anesthesia technique. The aim of the study was to determine thrombocyte function in Preeclamptic patients (P) compared to that in Healthy patients(h) by novel platelet function analysis techniques. After local institutional approval, we took written informed consent of 28 pregnant patients (14 H/14 P). Data on demographics, blood pressure, drug/herbal supplement use, and bleeding risks and laboraty values were collected. Venous blood samples were collected in hirudine, citrate and EDTA-tubes. We performed impedance-aggregrometry (multiplate ) with the following activators: ADP at stepwise increasing levels (0,5mmol/ 2,5mmol/ 7,5mmol), thrombine receptor test (TRAP) and collagen, PFA- 100 analysis with coll/adp and coll/epi, platelet count and mean platelet volume measurement (MPV). There were no significant differences with respect to age, gestational age and bleeding risk. Blood pressure and use of antihypertensive drugs differed significantly. For the H versus P groups PFA-100 analysis with coll/adp vs coll/epi test showed closure times of 83,8±25,1 vs 86.9±15,4 seconds and 100,8±26,2 vs 116,0±38,2 seconds respectively. With impedance-aggregometry for ADP the mean AUC at 0,5, 2,5 and 7,5 µmol were 33,0 ±24,3 vs 26,9±12,9, 68,0±29,4 vs 72,5±29,1 and 72,2±28,7 vs 88,1±29,6. Collagen and TRAP-test resulted in AUC 98,9±36,4 vs106,4±33,0 and 76,5±29,7 vs 99,6±26,2 (p<0.037). Platelet count was 266.4±79,4 vs 236,1±70,7 and MPV 8,5±1,0 vs 9,4±1,3 (p=0.05). TRAP is significantly higher in P. This could indicate higher thrombine pathway activity. A larger MPV points to higher platelet reactivity. To confirm this thesis and its impact on decision making a larger population has to be studied. Midazolam premedication for children undergoing T&A? J.M.K. van Fessem 1 A.A. van Maris 1 R.A.J.M. Willems 1 P.G.J. ten Koppel 1 A.J.W. Teunissen 1 R.J. Stolker 2 1 Maasstadziekenhuis, Rotterdam, the Netherlands 2 Erasmus MC, Rotterdam, the Netherlands Before undergoing surgery, children exhibit stress and anxiety, which can result in adverse physiologic and psychological effects. Besides the use of behavioral training methods, children often receive premedication. In this study, the effect of premedication with midazolam on children undergoing adenoidectomy and/or tonsillectomy (T&A) was prospectively investigated and compared with behavioral training. 192 children (2-10 years, ASA 1,2) presented for T&A were administered 0.5 mg/kg midazolam rectally (n=86) or received child and parental training before going to OR (n=106). Anesthesia was induced in presence of one parent and the trainer and continued after intubation with sevoflurane. Monitoring was applied according to standard practice. Postoperative medication (acetaminophen, diclofenac) was given according to local protocol. Parents and staff were asked to fill in our questionnaire concerning anxiety (before OR and induction), cooperation, drowsiness during the day of operation, PONV and diet intake back home.

16 14 nederlands tijdschrift voor anesthesiologie augustus '09 abstracts 2009 Children receiving midazolam were significantly more sleepy during the day, more cooperative in OR and less frightened before going to OR than children without premedication (P = < 0,001, using Chisquare statistical tests). However, there was no difference (P= 0.58) in being frightened at time of induction. The midazolam group suffered slightly more from PONV (P= 0.048), but there were no differences in diet intake (P= 0.30). Although premedicated children were more cooperative and less frightened before undergoing T&A, there was no difference prior to induction. This is possibly a result from preoperative training just before the operation. Since the children with midazolam are more sedated all day long and suffer more from PONV, premedication can better be omitted and preserved for special cases, if proper non-medical interventions are applied. A larger randomized study should be performed. Acute pain stress increases phosphorylation of DCLK-long in the rat Edinger-Westphal nucleus but not in the hypothalamic paraventricular nucleus T.P.H. Rouwette 1 L.T. Kozicz 2 N.F.M. Olde Loohuis 2 B. Gaszner 3 E. Vreugdenhil 4 G.J. Scheffer 1 E.W. Roubos 2 K.C. Vissers 1 W.J.J.M. Scheenen 2 1 UMCN, Nijmegen, the Netherlands 2 Department of Cellular Animal Physiology, Nijmegen, the Netherlands 3 Department of Anatomy, PÉCS, Hungary 4 Leiden/Amsterdam Center for Drug Research, Leiden, the Netherlands Acute pain stress leads to activation of the stress response, which, in turn, will induce changes in intracellular signaling in two stress-responsive centers, the paraventricular nucleus of the hypothalamus (PVN) and the midbrain non-preganglionic Edinger- Westphal nucleus (npew). The intracellular signaling pathways that are activated by this pain stressor are unknown. We have explored the possibility that members of the doublecortin-like kinase (DCLK) family of proteins are involved in pain stress-induced signaling in the PVN and the npew. Adult male Wistar rats were subjected to an acute pain stress protocol consisting of a formalin injection in the hindpaw and the npew and PVN were analyzed by immunohistochemistry and Western blotting for the phosphorylation status and intracellular localization of DCLK. Our results show that both DCLK-short and DCLK-long splice variants are present in the cytoplasm and proximal dendrites of neurons in the PVN and the npew. Of these isoforms, DCLK-long but not DCLKshort is phosphorylated in its serine/proline-rich domain. Furthermore, we demonstrate that phosphorylation of DCLK-long in the npew is increased by acute pain stress, whereas DCLK-long phosphorylation in the PVN remains unaffected. This is the first report revealing that DCLK isoforms in the PVN and npew occur in the adult mammalian brain and that the regulatory pathways of DCLK-long differ between these two stress-sensitive brain centers.

17 augustus '09 nederlands tijdschrift voor anesthesiologie 15 poster walk around Does a field block reduce the incidence of postoperative pain, nausea and vomiting in oncologic breast surgery? P.M.L.E. Riezebos M.M.J. Snoeck L.J.A. Strobbe Canisius-Wilhelmina Ziekenhuis, Nijmegen, the Netherlands Breast surgery performed under general anesthesia is associated with a high incidence of postoperative nausea and vomiting (PONV). Prevention strategy, anti-emetic therapy and measures to provide opioid sparing reduce the incidence of PONV. A field block of the breast (mamma field block) might reduce postoperative pain and therefore opioid consumption. The aim of this study was to determine the efficacy of a multimodal approach in combination with a mamma field block to prevent PONV. In this prospective randomised doubleblind trial a mamma field block was performed under standardized general anesthesia in 84 ASA 1-2 patients scheduled for oncologic breast surgery with either 50 ml of ropivacaine 0,375 % (group A) or 50 ml NaCl 0,9 % (group B). Patients were prophylactic treated with an anti-emetic multimodal regimen using propofol for anesthesia and a combination of dexamethason and droperidol. Postoperative paracetamol and PCA morphine were prescribed. A validated risk score was used to predict the occurrence of PONV. Primary endpoints were pain scores (NRS), opioid consumption, occurrence of PONV (NRS) and use of rescue anti-emetics throughout the 24 hour study period. The predicted risk score of PONV was 38 % in group A (n=43) and 36% in group B (n=41). There was no difference in pain scores or opioid consumption between the groups. The incidence of PONV was 0 % in group A and 0,07 % in group B. Six patients received a rescue anti-emetic drug. The incidence of PONV using a multimodal regimen was very low. A mamma fieldblock using 50ml ropivacaine 0,375 % had no significant effect on pain scores and opioid consumption. Effects of sympathetic arousal and interoceptive awareness on pain in fibromyalgia: a feasibility study D.S. Veldhuijzen 1 A.J.M. van Wijck 1 R. Geenen 2 J.W.G. Jacobs 1 C.J. Kalkman 1 1 UMC Utrecht, Utrecht, the Netherlands 2 Utrecht University, Utrecht, the Netherlands Fibromyalgia is characterized by chronic widespread pain. The mechanisms underlying this syndrome remain largely unknown. We hypothesize that awareness of bodily sensations and heightened sympathetic nervous system activity are mediators of pain augmentation in fibromyalgia. A pilot study was performed to test the feasibility and to calculate power for conducting a larger study on the associations between altered sympathetic nervous system functioning, interoceptive awareness, and pain in fibromyalgia. In 8 female fibromyalgia patients and 8 matched healthy women, sympathetic nervous system activity was assessed by skin conductance measurements. The individual s sensitivity to perceive bodily sensations is referred to as interoceptive awareness; it was operationalized by the individual s ability to accurately perceive one s heartbeat. Pain thresholds were assessed using a pressure algometer. Patients and healthy controls were able to perform the interoceptive task and to endure the pain measurement. Pressure pain thresholds were found to be significantly lower for patients compared to controls (1.53 versus 3.66 kg/cm2, respectively; p< 0.001). A trend towards significance was observed for higher interoceptive awareness scores in healthy subjects compared to fibromyalgia patients (0.88 versus 0.74, respectively; p=0.052). In general, higher interoceptive awareness correlated with higher pain thresholds (r = 0.61). Sample sizes were too small to examine this at the subgroup level. No significant effects were found for skin conductance levels. On the basis of this study it could be calculated that a properly powered study to assess differences in skin conductance levels between groups would require 77 participants in each group with a medium effect size (f2=.15), alpha-level of.05, and power of.80.

18 16 nederlands tijdschrift voor anesthesiologie augustus '09 abstracts 2009 This study demonstrated the feasibility of investigating group differences in pain thresholds as well as interoceptive awareness, while the analyses of differences of autonomic nervous system activity requires a larger sample size. S(+)-ketamine effect on chronic pain and experimental acute pain in Complex Regional Pain Syndrome type 1 patients M.J. Sigtermans 1 J. van Cosburgh 2 A. Dahan 1 1 LUMC, Leiden, the Netherlands 2 Reinier de Graaf Groep, Delft, the Netherlands The aim of the study was to explore the analgesic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine in acute experimental versus chronic spontaneous pain in Complex Regional Pain Syndrome type 1 (CRPS-1) patients. Ten patients suffering from chronic CRPS-1 and with a Visual Analogue pain Score (VAS) of > 5 were recruited. Seven intravenous 5-min low-dose S(+)-ketamine infusions with increasing doses at 20-min intervals were applied. Spontaneous pain ratings and VAS responses to experimental heat stimuli were obtained during infusion and for 3-h following infusion. For comparative reasons, the effect of S(+)-ketamine on VAS response to experimental pain was obtained in 12 healthy volunteers. Ketamine produced potent analgesia in patients with a significant VAS reduction from 6.2 ± 0.2 to 0.4 ± 0.3 cm at the end of infusion. Analgesia persisted beyond the infusion period (VAS = 2.8 ± 1.0 cm at 5-h), when measured plasma ketamine concentrations were low (< 100 ng/ml). In patients and volunteers, ketamine had a similar dose-dependent antinociceptive effect on experimental pain that ended immediately upon the termination of infusion. Discussion The data indicate that while ketamine s effect on acute experimental pain is driven by pharmacokinetics, its effect on CRPS pain persisted beyond the infusion period when drug concentrations were below the analgesia threshold for acute pain. This indicates a disease modulatory role for ketamine in CRPS-1 pain, possibly via desensitization of NMDAR in the spinal cord or restoration of inhibitory sensory control in the brain. Fentanyl induces hyperalgesia in humans and mice E.Y. Sarton A. Dahan J. Grefkens B. Kest M. Boom E. van Dorp LUMC, Leiden, the Netherlands Fentanyl is an opioid frequently used as potent analgesic to treat acute perioperative pain and chronic pain via transdermal applications. There are indications that opioids produce hyperalgesia via pro-nociceptive metabolites. For example, morphine produces hyperalgesia via its two main metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Fentanyl does not have any active metabolites. We therefore tested this opioid in three separate models of analgesia/hyperalgesia. Model 1. The effect of fentanyl in triple knockout mice (TKO mice devoid of opioid receptors) using a tail immersion test. Model 2. The effect of fentanyl in mice treated with naltrexone using the tail immersion test; Model 3. The effect of fentanyl in humans using heat pain stimuli. The results indicate potent and long lasting hyperalgesia in TKO mice and control mice treated with naltrexone in both acute and chronic infusion schemes. In contrast, control mice treated with placebo displayed no hyperalgesia. In humans analgesia preceded hyperalgesic responses after fentanyl only when the subjects were tested in the early hours of the morning (2 AM). Our data indicate that a) fentanyl hyperalgesia is not related to opioid-receptor activation, and b) that pronociceptive metabolites are not a prerequisite for opioid-hyperalgesia. We further tested the effect of MK801 (an NMD receptor antagonist) in our mice and observed that MK801 effectively prevents development of fentanyl hyperalgesia. Similar observations were made earlier for morphine and M6G. This then suggest that not the opioid receptor but the NMDA receptor is the site of action of opioid hyperalgesia.

19 augustus '09 nederlands tijdschrift voor anesthesiologie 17 poster walk around Paravertebral block for analgesia after major oncologic breast surgery: a comparison of continuous paravertebral block, single shot paravertebral block, and single shot wound infiltration E.A.C. Bouman H.M.S. Theunissen A.G. Kessels M.A.E. Marcus H.F. Gramke Maastricht University Medical Centre + (MUMC+), Maastricht, the Netherlands Paravertebral block has been succesfully used for postoperative analgesia after breast surgery. The aim of this study was to evaluate whether a continuous paravertebral block with a catheter technique is superior to single shot paravertebral block or single shot wound infiltration. 25 patients were included in this prospective, open, randomized controlled trial. Group I received a single shot paravertebral block with 0.25ml/kg ropivacaine 0.75% preoperatively. Group II received a paravertebral block with 0.25ml/kg ropivacaine 0.75% followed by patient controlled paravertebral analgesia with ropivacaine 0.2% during 48 hours. Group III had local wound infiltration with bupivacaine 0.25% at the end of surgery. General anesthesia was provided during surgery to all patients. A 100mm visual analogue scale (VAS) was used for measuring pain intensity. Besides side-effects and complications of anesthesia were recorded. Overall pain intensity was low in all three groups. VAS-scores were significantly higher in group I compared to group III in the morning and afternoon on the day after the operation (p=0.005 and p=0.021). Except for the first measurement VAS-scores were higher in group III compared to group II, but this difference was only statistically significant on the morning after surgery (p=0.041). We did not record serious sideeffects of any technique. Postoperative analgesia after major breast surgery was succesful in all three groups. Our results do not favour single shot paravertebral block as routine technique for postoperative analgesia after major breast surgery. Predicting the time course of sensory block after intrathecal injection of lidocaine M.A. Holtkamp 1 D.J. Eleveld 1 A.M. van Oort 1 S. Schiere 2 1 UMCG, Groningen, the Netherlands 2 Tjongerschans, Heerenveen, the Netherlands Lidocaine is a short-acting local anesthetic frequently used for outpatient procedures. A number of patient and non-patient factors have been suggested to influence the dose-effect relationship of lidocaine, but the relationships are not clear and a wide dose range is used by Dutch anesthesiologists [1]. In this observational study we try to develop a pharmacodynamic model to describe the time course of sensory blockade. We also investigated the incidence of transient neurologic symptoms (TNS). In this observational study 120 patients were included. All patients received spinal anesthesia with isobaric lidocaine 2%. The technique, dose and needle were chosen by the anesthesiologist performing the spinal puncture. The sensory block was tested with pinprick. Patients were called to answer questions regarding TNS. Prediction of the time course of sensory blockade was performed using a one-compartment PK model with absorption and a sigmoid PD model coded to dermatome level. Model estimation was performed using NONMEM (6.2) and PLT-Tools (2.0). Inter-individual variability was large, with a sensory block level ranging from L5-C4, a median blockheight of T9, and a median onset of 13 minutes (1-87 min). Posthoc individual prediction accuracy was good (SD 0.89 dermatomes) but population predictions were poor with a standard deviation in predicted blockheight of plus or minus 1.2 dermatome. None of the observed patient covariates were correlated to maximal achievable effect (PD model Emax). TNS was found in 10.8% of patients (95% CI 5-18%). The investigated patient covariates do not allow accurate prediction of sensory blockade in an individual before the initial dose has been given. reference 1. Krul-Sterk A., et al.eur J of Anaesthesiol. 2009; 26:

20 18 nederlands tijdschrift voor anesthesiologie augustus '09 abstracts 2009 Chronic neuropathic pain: structural changes in the superficial dorsal spinal cord R. Deumens R.J.P. Jaken M.A.E. Marcus E.A.J. Joosten Universitair Medisch Centrum Maastricht, Maastricht, the Netherlands Chronic neuropathic pain (CNP) is common after neuropathy and refractory to treatment due to a limited understanding of the underlying mechanisms. Structural changes in the dorsal spinal cord have been proposed to relate to CNP following nerve injury. More specifically, noninjured nociceptive afferents were found to sprout in the superficial dorsal horn of denervated spinal segments. However, the specific termination pattern of these nociceptive afferents remains unclear. Therefore, we hypothesize that nociceptive afferents sprout into a specific layer of the dorsal spinal cord, which is occupied with PKCγ+ interneurons normally receiving exclusively non-nociceptive inputs. This aberrant input may underlie CNP following L5 spinal nerve transection. Adult Sprague-Dawley rats received a L5 spinal nerve transection. Mechanical allodynia was assessed by measuring hind paw withdrawal threshold to tactile stimuli before and up to 21 days after injury. Immunohistochemical staining of PKCγ+ interneurons and sprouting primary afferents (GAP-43 immunoreactivity) was performed on several days following L5 spinal nerve transection. Animals displayed mechanical allodynia of the ipsilateral, but not of the contralateral hind paw up to 21 days post-injury. Immunohistochemical analysis at different survival times following L5 spinal nerve transection revealed an increased GAP-43 immunoreactivty in the ipsilateral dorsal horn compared to the contralateral dorsal horn. More specifically, sprouting in the PKC+ layer was more pronounced on the ipsilateral side compared to the contralateral side. We conclude that CNP after L5 spinal nerve transection is associated with sprouting of primary afferents. Moreover, sprouting occurred into regions normally not involved in nociceptive processing, which may underlie the CNP. However, the nature of these sprouting afferents needs further investigation to gain further knowledge, which may aid the development of novel therapies to more effectively treat CNP. Spinal cord stimulation reduces the neuronal metabolism of the superficial dorsal horn (DH) after spinal cord stimulation (SCS) in rats with nerve injury induced pain. (preliminary data) H. Smits 1 T. Pederzani 2 J.L.M. Jongen 2 E.A.J. Joosten 1 F. Huygen 2 1 Pain Management and Research Center, Anesthesiology department, Maastricht, the Netherlands 2 Erasmus MC, department of pain treatment, Rotterdam, the Netherlands SCS is an established treatment for intractable neuropathic pain, especially Complex Regional Pain Syndrome type 1. The mechanisms of action of SCS are partially understood and more experimental research on this subject is needed. In the present study we performed an online in vivo analysis of the mitochondrial metabolism of superficial dorsal horn neurons in neuropathic pain after spinal cord stimulation, using Autofluorescent Flavoprotein Imaging (AFI). Mitochondrial oxidized flavoproteins have the ability to absorb blue spectrum ( nm) photons. This leads to an immediate emission of green spectrum photons ( nm), whose intensity (detected by a CCD camera) is a direct measure of neuronal metabolic activity. In a rat (n = 9) model of nerve injury induced pain, allodynia was induced and quantified using the von Frey test. 14 Days post nerve injury the animals were anesthesized with urethrane and the spinal cord was exposed by a laminectomy at T13 (dura left intact).the animals were paralysed and mechanically ventilated and after 4 baseline AFI recordings, they received 30 minutes of SCS at T13 vertebral level (f 50 Hz, pulsewidth 0,2 ms, current 0,2 ma). After this, the AFI intensity was measured every 5 minutes for up to 65 minutes. A significant (P< 0.018) reduction in AFI intensity compared to baseline was measured 5 minutes after cessation of spinal cord stimulation, indicating a short reduction in superficial DH neuronal metabolism after SCS.