anesthesiologie Nederlands tijdschrift voor Wetenschap special volume 22, september Selectie van abstracts C. Boer Abstracts Wetenschapsdag 2010

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Nederlands tijdschrift voor

anesthesiologie Wetenschap special volume 22, september 2010

4

• Selectie van abstracts C. Boer

• Abstracts Wetenschapsdag 2010

Dr. M. Klimek, hoofdredacteur Dr. C. Boer, plaatsvervangend hoofdredacteur

Officiële uitgave van de Nederlandse Vereniging voor Anesthesiologie

2010 Eldering_NTvA 04 v3.indd 1

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nederlands tijdschrift voor anesthesiologie september ’10

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inhoud Nederlands tijdschrift voor

anesthesiologie Coverbeeld: Shutterstock

volume 22 Nummer 4 september 2010

editorial

5

Selectie van abstracts C. Boer

abstracts wetenschapsdag 2010 o r a l p r e s e n tat i on

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Benzethonium increases the cytotoxicity of S(+)ketamine in lymphoma, neuronal and glial cells F. Stevens, R. Werdehausen, N. Gaza, H. Hermanns, M.W. Hollmann, S. Braun o r a l p r e s e n tat i on

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C.W. Doornebal, M. Ciampricotti, Cheei-Sin Hau, M.W. Hollmann, J. Jonkers, K.E. de Visser 8

Effect of spinal cord stimulation on tactile hypersensitivity is potentiated by a subeffective dose of ketamine in an animal model of chronic neuropathic pain M. Truin, S.P.M. Jannsen, R. Deumens, M. van Kleef, E.A.J Joosten o r a l p r e s e n tat i on

The effect of helium on the immune system ex-vivo G.T.M.L. Oei, K.F. Smit, D. van de Vondervoort, N.C. Weber, M.W. Hollmann, B. Preckel o r a l p r e s e n tat i on

C.E. van den Brom, R.A. Bouwman, M.H. Graeler, D.M. Ouwens, M. Diamant, C. Boer o r a l p r e s e n tat i on

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M. Niesters, E.Y. Sarton, A. Dahan 10

groep 1: pijn

Time-dependent plasticity of the spinal GABAergic system in relation to the degree of neuropathic pain

A.A. Fiddelers, N.M.L. Veldhorst, P-H.M. Van der Kuy, C. Neef, M.A.E. Marcus

S.P.M. Janssen, M. Truin, M. Van Kleef, Elbert A. Joosten

posterdiscussion

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Myocardial contrast echocardiography for the study of perioperative myocardial perfusion

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S.G.A. van Neerven, E.A.J. Joosten, R. Deumens groep 1: pijn

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Pain symptoms accompanying chronic post sternotomy pain, a cross-sectional cohort study N.J. van Leersum, R.L. van Van Leersum, H.F. Verwey, R.J.M. Klautz

L. Knaepen, R. Deumens, D. Tibboel, J. Patijn, E.A.J. Joosten

M.C.A. Boom, J. Grefkens, E.L.A. van Dorp, E. Olofsen, L.P.H.J. Aarts, A. Dahan, E.Y. Sarton

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Role of corticotropin-releasing factor and urocortin 1 systems in pain-induced maladaptation and comorbid diseases

B.J.W. Thomassen, L.D. Pool, R.E. van der Flier, R.D. Stienstra, B.A. in ‘t Veld

M.J. Sigtermans, E. Olofsen, A. Dahan

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Intrathecal delivery of VEGF165 following experimental spinal cord injury results in modest attenuation of mechanical allodynia

Safety of retransfusing shed blood after local infiltration analgesia in total knee arthroplasty

A reinforced microglial response as as mechanism underlying long-term changes in paijn sensitivity after neonatal repetitive pain

groep 1: pijn

groep 1: pijn

Prediction of early liver dysfunction after orthotopic liver transplantation using indocyanine green plasma disappearance rate

groep 1: pijn

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Opioid Chronopharmacology: Influence of Timing of Infusion on Fentanyl’s Analgesic Efficacy

C.S.E. Bulte, J. Slikkerveer, O. Kamp, S.A. Loer, C. Boer, R.A. Bouwman

Population pharmacokinetic-pharmacodynamic modeling of ketamine- induced pain relief of chronic pain


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Pharmacokinetics of a highly concentrated intranasal midazolam spray in healthy adult volunteers

groep 1 - pijn

Effect of ketamine on endogenous pain modulation in healthy volunteers posterdiscusson

S.F.J. van Gorp, E.A.J. Joosten, P. Martínez-Martínez, M. Losen, M. de Baets, M. van Kleef, R. Deumens

posterdiscussion 9

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I. de Liefde, G.M.J.M. Welten, H.J.M Verhagen, R.T. van Domburg, R.J. Stolker, D. Poldermans

J.J. Vos, T.W.L. Scheeren, J.K.G. Wietasch

Reversion of high-fat diet normalizes myocardial function and sphingolipid levels in rats

groep 1: pijn

Translational research on central neuropathic pain and neuroinflamation after experimental spinal cord injury

posterdiscussion 8

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Increased perioperative complications after major vascular surgery in patients with a preoperative abnormal exercise blood pressure response

posterdiscussion

The impact of morphine on tumor progression and metastasis formation in a preclinal mouse model of metastatic breast cancer

o r a l p r e s e n tat i on

posterdiscussion

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T.P.H. Rouwette, W.J.J.M Scheenen, E.W. Roubos, T. Kozicz, K.C. Vissers groep 2: divers

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Decision support reduces PONV incidence in a general surgical population F.O. Kooij, T. Klok, M.W. Hollmann, J.E. Kal groep 2: divers

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Arterial and Venous Pharmacokinetics of Morphine-6-Glucuronide and Impact of Sample Site on Pharmacodynamic Parameter Estimates E.L.A. van Dorp, E. E. Olofsen, A. Dahan

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september ’10 nederlands tijdschrift voor anesthesiologie

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groep 2: divers

inhoud 18

Increased renal microvascular endothelial responsiveness to LPS in aged mice F.M. Wulfert, M. Meurs, van, N.F. Neng, R.M. Jongman, P. Heeringa, J.G. Zijlstra, M.M.R.F. Struijs, G. Molema groep 2: divers

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Pulse Transit Time to assess the mechanism involved in CRPS-induced vasomotor dysfunction

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Postoperative Urinary Retention: a biased diagnosis? 21

Endotracheal intubation using videolaryngoscopy causes less cardiovascular responses compared to classic direct laryngoscopy R.L.J.G. Maassen, B. Pieters, B. Maathuis, J. Serroyen, M.A.E. Marcus, A.A.J. Van Zundert g r o e p 3 : c a r d i o vasculair

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Withdrawal of low dose aprotinin from anti-fibrinolytic therapy with tranexamic acid is associated with increased blood loss and transfusion requirements in cardiothoracic surgery M.I. Meesters, A.B.A. Vonk, J.W.A. Romijn, E.K. Jansen, C. Boer

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K.W.L. van Deutekom, A.B.A. Vonk, R.A. Bouwman, S.A. Loer, C. Boer 24

Development of phosphorescent nanovesicles for measuring microvascular PO2 S.I.A. Bodmer, M. Heger, M. Broekgaarden, T. Johannes, D. Gommers, R.J. Stolker, E.G. Mik groep 3: cardiovasculair

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Crystalloid Fluid restriction during pancreatic surgery has no measurable effect on delayed gastric emptying: the results of a doubleblinded prospective trial (EPOR) G. van Samkar, O.R.C. Busch, R.J. Bennink, W.J. Eshuis, T.M. Van Gulik, M.G.W. Dijkgraaf, B. Preckel ,S.G. De Hert, D.J. Gouma, M.W. Hollmann 28

R.J. Willems, A. Van Zundert, R. Maassen, R. Lee groep 4: divers

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In vitro testing of a computer-driven model for Sevoflurane infusion through AnaConDa® C.R.M. Barends, J.K. Oosterhuis, T. De Smet, M. Enlund, M.M.R.F Struys groep 4: divers

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The effects of epidural analgesia on delivery in a dutch teaching hospital: does the rate of caesarean section or instrumental delivery increase? P. Bruins, A.C. Werger, L.S.M. Ribbert, M.E. Kars, H.P.A van Dongen groep 4: divers

Helium induced early and late preconditioning in human endothelium

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Can sugammadex save a patient in a simulated ‘cannot intubate cannot ventilate’ situation at a large teaching hospital?

K.F. Smit, G.T.M.L. Oei, N.C. Weber, E.S. Stroes, M.W. Hollmann, B. Preckel groep 4: divers

M.F. Grapenthin, A.R. Absalom, J.K.G. Wietasch, R.J. Steur

groep 4: divers

Perioperatieve prohormone levels of atrial natriuretic peptide, adrenomedullin and vasopressin during cardiac surgery: an explorative study

groep 3: cardiovasculair

L.S. Wagenaar, J.K.G. Wietasch, T.A. Brouwer

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A Macintosh laryngoscope blade for videolaryngoscopy reduces stylet use in patients with normal airways

E.H.A. Maas, I.H.F. Herold, M.P.J. Kuenen, A.J.G.H. Bindels, M. Mischi, H.H.M. Korsten groep 3: cardiovasculair

M.C. Kortekaas, S.P. Niehof, M.H.N. Van Velzen, R.J. Stolker, F.J.P.M. Huygen

groep 2: divers

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Blood volume measurements by contrast enhanced ultrasound and thermodilution: an in vitro comparison

R.M. van Bockel, E.W. van den Bosch, M.M.R.F. Struys, R.H.G van den Brom

groep 2: divers

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M.C. Timmerman, R. Van Oerle, Y.M.C. Henskens, M.A.E. Marcus, M.D. Lancé groep 3: cardiovasculair

Recovery discharge criteria after spinal anesthesia with articaine in day care surgery

groep 4: divers

Ultrasound assistance for positioning of epidural catheters in neonates and infants

groep 4: divers

Does pneumatic tube transport influence TEG and ROTEM thromboelastography/ -metry?

J.W. Hol, R.J. Stolker, M. Klimek, F. van Lier, D. Stronks, D. Fekkes

groep 2: divers

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A.G.E. van der Spoel, R.A. Bouwman, A.C. Folkers, A.J. Voogel, C. Boer groep 3: cardiovasculair

The effects of major and minor surgery on the tryptophan kynurenine pathway, neopterin and IL-6

groep 2: divers

groep 3: cardiovasculair

Comparison of non-invasive continuous arterial waveform analysis (Nexfin HD) with transthoracic Doppler echocardiography for monitoring of cardiac output

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M.M.A. Bisschops, C Holleman, J.M. Huitink

Effects of helium on H2O2 induced damage in HUVEC D. van de Vondervoort, K.F. Smit, M.W. Hollmann, B. Preckel, N.C. Weber

2010)

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colofon Het Nederlands Tijdschrift voor Anes thesiologie is het officiële orgaan van de Nederlandse Vereniging voor Anesthe siologie. Het stelt zich ten doel om door middel van publicatie van overzichts artikelen, klinische en laboratorium studies en casuïstiek, de verspreiding van kennis betreffende de anesthesi ologie en gerelateerde vakgebieden te bevorderen. REDACTIE

Kernredacteuren: Dr. C. Boer, Prof. Dr. A. Dahan, Dr. H. van Dongen, Dr. H.G.D. Hendriks, 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.A. Loer, Dr. S. Schiere, Dr. B. in het Veld, Dr. K. Vissers, Dr. J.K.G. Wietasch, 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 e-mail: [email protected]

REDACTIE-ADRES

Nederlands Tijdschrift voor Anesthesiologie, mw. W. van Engelshoven, Academisch Ziekenhuis Maastricht, Afdeling Anesthesiologie, Postbus 5800, 6202 AZ Maastricht; [email protected] internet: www.anesthesiologie.nl

INZENDEN VAN KOPIJ

Richtlijnen voor het inzenden van kopij vindt u op www.anesthesiologie.nl of kunt u opvragen bij de redactie of de uitgever.

OPLAGE 2.500 exemplaren, 5x per jaar Het NTvA wordt uitsluitend toegezonden aan leden van de NVA. Adreswijzigingen: Nederlandse Vereniging voor Anesthesiologie, Postbus 20063, 3502 LB Utrecht, tel. 030-2823385, fax 030-2823856, e-mail [email protected]

PRODUCTIE

Bladcoördinatie: Drs. Thomas Eldering (023-5259332) Ontwerp: Dimitry de Bruin Eindredactie: Monique de Mijttenaere

AUTEURSRECHT EN AANSPRAKELIJKHEID

© De Stichting tot Beheer van het Nederlands Tijdschrift voor Anesthesiologie 2009. Nederlands Tijdschrift voor Anesthesiologie® is een wettig gedeponeerd woordmerk van de Nederlandse Vereniging voor Anesthesiologie. Alle rechten voorbehouden. Niets uit deze uitgave mag worden verveelvoudigd, opgeslagen in een geautomatiseerd gegevensbestand of openbaar gemaakt, in enige vorm of op enige wijzen, hetzij elektronisch, mechanisch, door fotokopieën, opnamen of enige andere manier, zonder voorafgaande schriftelijke toestemming.


editorial Christa Boer Plaatsvervangend hoofdredacteur

Selectie van abstracts

G

eachte lezer,

Zeven jaar geleden nam ik voor het eerst deel aan de organisatie van de NVA Wetenschapsdag als lid van het Organiserend Comité Wetenschapsdag onder leiding van Gert-Jan Scheffer. De verwachtingen waren gespannen, maar de dag werd een groot succes. Het aantal deelnemers en bezoekers, de kwaliteit van de inzendingen en het niveau van de discussies steeg tijdens de daaropvolgende edities tot een hoog niveau. De NVA Wetenschapsdag biedt een platform aan jonge onderzoekers uit de experimentele en klinische setting, en na zeven jaar kunnen we concluderen dat het aantal (zeer) jonge onderzoekers dat aan deze dag deelneemt nog steeds toeneemt. Deze toename is onder andere een reflectie van de groeiende groep jonge anesthesiologen die structureel betrokken is bij onderzoek binnen ons vakgebied. Daarnaast is er in toenemende mate sprake van studenten geneeskunde die onderzoek doen binnen de perioperatieve setting en vervolgens doorstromen naar de opleiding anesthesiologie. De vraag is welke veranderingen hebben geleid tot de groeiende interesse in onderzoek binnen ons vakgebied. Niet alleen de verplichte wetenschappelijke bijdrage tijdens de opleiding tot anesthesioloog en de inzet van academische en perifere ziekenhuizen voor wetenschappelijk onderzoek binnen de OOR hebben hieraan bijgedragen. We observeren tevens een uitbreiding van de ingezonden manuscripten voor publicatie in het NTvA en een stijging in het aantal subsidies van organisaties als ZonMW en collectebusfondsen die worden toegekend aan een onderzoeksproject binnen de anesthesiologie. Maar bovenal is er een zichtbare toename in de interesse voor het doen van wetenschappelijk onderzoek

onder AIOS en stafleden anesthesiologie. Immers, zonder onderzoek is er geen innovatie en kennisvermeerdering mogelijk, en hierop wordt in verschillende academische en perifere ziekenhuizen geanticipeerd. De groeiende aandacht voor wetenschappelijk onderzoek binnen de opleiding tot anesthesioloog biedt niet alleen de nieuwe generatie stafleden handen en voeten voor het opzetten van eigen projecten binnen de afdeling, maar motiveert ook ervaren stafleden om te participeren in wetenschappelijk onderzoek. Daarmee is een belangrijke stap gezet richting integratie van wetenschap met opleiding en klinische praktijk binnen het vakgebied Anesthesiologie. Dit jaar ontving het Organiserend Comité Wetenschapsdag dusdanig veel inzendingen voor de NVA Wetenschapsdag dat een selectie van abstracts moest worden gemaakt. De voor u liggende uitgave van het NTvA is geheel gewijd aan deze abstracts en aan de NVA Wetenschapsdag in het algemeen. Voor mij is deze uitgave van het NTvA niet alleen een prachtige illustratie van het stijgende niveau van perioperatief wetenschappelijk onderzoek in Nederland, maar tevens de eerste uitgave waaraan ik mag meewerken als plaatsvervangend hoofdredacteur. Ik hoop daarmee in de komende jaren nog op veelzijdige wijze te kunnen bijdragen aan het verbeteren van de infrastructuur en het omgevingsklimaat voor het doen van perioperatief wetenschappelijk onderzoek. Een voorbeeld hiervan vormt de geaccrediteerde nascholing die het NTvA in de toekomst zal aanbieden met als doel de kennis te verbreden rondom niet-alledaagse thematiek en nieuwe ontwikkelingen binnen ons vakgebied. Ik wens u veel plezier met het lezen van deze editie van het NTvA. Christa Boer

10-09-10 12:02

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oral presentations

oral presentat i o n

Benzethonium increases the cytotoxicity of S(+)-ketamine in lymphoma, neuronal and glial cells F. Stevens1, R. Werdehausen2, N. Gaza2, H. Hermanns2, M.W. Hollmann1, S. Braun2 1 AMC, AMSTERDAM, the Netherlands 2 Universitätskliniken Düsseldorf, Düsseldorf, Germany

Introduction Ketamine has been demonstrated to be neurotoxic in animals as well as in patients. Preservatives added to ketamine have been accused to induce neurotoxicity. Therefore, we investigated whether the most widely used preservative of ketamine - benzethonium chloride - enhances the toxicity of S(+)-ketamine in vitro in lymphoma, neuroblastoma cells and primary astrocytes.

Methods Human Jurkat T-Lymphoma-, neuroblastoma cells (SHEP) and primary rat astrocytes were incubated for 24h with commercially available S(+)-ketamine containing benzethonium, as well as only with S(+)-ketamine or benzethonium chloride alone. The rate of early- and late-apoptotic cells was evaluated after double-staining with Annexin V and 7AAD by flowcytometry. In a second step, the

additivity of toxicity was investigated in neuroblastoma cells and astrocytes by means of isobolograms using a XTT assay to measure overall viability (mitochondrial activity). All experiments were performed three times and the results are presented as mean ± CI (95%).

Results In all cell types benzethonium increased the toxicity of S(+)-ketamine. The main mechanism of toxicity was apoptosis as displayed by flowcytometry. The isobolograms of combined toxicity of benzethonium and S(+)-ketamine demonstrated additive toxicity in neuroblastoma cells (Fig. A) and astrocytes (Fig. B) . The straight black line connects the

LD50 of S(+)-ketamine and benzethonium as seen during pure additivity. The CI (95%) is represented by dashed lines. The black data point indicates the calculated halfmaximal concentrations (LD50) resulting from the experimentally observed doseresponse relationship of S(+)-ketamine and benzethonium in combination.

Conclusion We conclude that benzethonium increases the local toxicity of ketamine in cells of hematopoetic, neuronal and glial origin in an additive manner. Therefore, neuraxial application of ketamine alone and especially in solutions containing benzethonium should be restricted.


The impact of morphine on tumor progression and metastasis formation in a preclinal mouse model of metastatic breast cancer C.W. Doornebal1, M. Ciampricotti1, Cheei-Sin Hau1, M.W. Hollmann2, J. Jonkers1, K.E. de Visser1 1 Netherlands Cancer Institute, Amsterdam, the Netherlands 2 Academic Medical Center, Amsterdam, the Netherlands

Introduction Opioid analgesics are the mainstay and most effective treatment of cancer-related pain. Nevertheless, two clinical studies recently reported an increased risk of recurrence or metastasis formation in surgical breast- and prostate cancer patients treated with morphine. These potentially deleterious side-effects might be explained by morphine’s proangiogenic and immune


inhibitory actions. Our aim was to test this hypothesis utilizing a novel preclinical mouse model of breast cancer metastasis formation.

Methods The effects of morphine on tumor progression and metastasis formation are tested in a transplantation-based mouse model of metastatic breast cancer. In this model, donor tumors derived from a conditional mouse model of spontaneous breast cancer formation are transplanted into mammary glands of wild-type FVB/N mice. Transplanted tumors are subsequently allowed to establish, after which mastectomy is performed. Following surgery, mice develop clinically overt

metastases for which they eventually need to be sacrificed. Using this model, morphine’s impact on two distinct phases in tumor development are studied by treating mice either during (a) primary tumor development or (b) post surgery while they are at risk for metastasis formation.

Results Preliminary results suggest that effective analgesic doses of morphine do not accelerate primary tumor growth in our model (median tumor latencies 29 vs. 35 days for NaCl0.9% and morphinetreated animals, respectively). Likewise, immune profiles of peripheral blood and tumors were not quantitatively affected by morphine (influx of CD45+ cell into

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abstracts 2010 the tumor: 17.9 ±3.1% vs. 16.7±1.5% for control and morphine-treated animals, respectively). We are currently addressing whether morphine has an effect on metastasis formation in vivo.

Conclusions This study might provide a significant contribution to the recently evolved controversy regarding the use of morphine in cancer patients. In addition, potential

effects of morphine on tumor progression and metastasis formation can be studied mechanistically in our model.


Effect of spinal cord stimulation on tactile hypersensitivity is potentiated by a sub-effective dose of ketamine in an animal model of chronic neuropathic pain M. Truin, S.P.M. Jannsen, R. Deumens, M. van Kleef, E.A.J Joosten AZM, MAASTRICHT, the Netherlands

Introduction Although Spinal Cord Stimulation (SCS) is an established therapy for chronic neuropathic pain, still 60% of patients do not respond adequately to trial stimulation. These so called “non-responders”do not receive a permanent implantation for pain relief. The induction and maintenance of central sensitization, the origin for (chronic) neuropathic pain, is thought the be the resultant of the activation of the N-MethylD-Aspartate (NMDA) receptor in the dorsal horn. Blocking the NMDA receptor has been proven to attenuate neuropathic pain,

although the undesirable side effects limits its use. The effect of SCS on the NMDA receptor is unknown and we therefore wanted to elucidate the possible role of the NMDA receptor in SCS induced pain relieve.

Methods Rats (n=15) received a partial ligation of the sciatic nerve for the induction of neuropathic pain. Behavioral signs of neuropathic pain were measured using von Frey monofilaments. After implantation of the electrodes, animals received 30 minutes of SCS (frequency 50 Hz, pulse width 0.2 ms). Non-responders to SCS received an intrathecal individual determined subeffective dose of the NMDA receptor antagonist ketamine and subsequently received SCS. Responders to SCS also received their individual determined subeffective dose of ketamine.

Results All 15 animals developed chronic neuropathic pain. From these neuropathic animals 8 (53%) did not respond to SCS. However, the combined treatment of SCS and sub-effective dose of ketamine resulted in a significant pain relieve in all these eight previously non-responders. In the animals previously responding to SCS (n=7), subeffective ketamine combined with SCS resulted in a prolonged attenuation of the neuropathic pain compared to SCS alone.

Conclusion A sub-effective dose of intrathecal ketamine is able to convert non-responders to SCS into responders to SCS and prolong pain relieve.


The effect of helium on the immune system ex-vivo G.T.M.L. Oei, K.F. Smit, D. van de Vondervoort, N.C. Weber, M.W. Hollmann, B. Preckel

Il-8 in whole blood after stimulation with lipopolysaccharide (LPS).

AMC, AMSTERDAM, the Netherlands

Methods

Introduction Experimental studies show that helium protects myocardial and neuronal tissue against ischemia/reperfusion damage. If helium is introduced to protect against clinical ischemia/reperfusion injury, it has to be evident that no effects on cytokines and chemokines pivotal for the defense against bacterial infections exist. From other organ protective inhalational gases such as volatile anesthetics and xenon, immunomodulatory effects are known. We investigated whether a 30-minute episode of helium breathing affects proinflammatory cytokines TNFalpha, IL-1beta and IL-6 and chemokine


This study with cross-over design was approved by the ethical committee of the Academic Medical Center (METC). Healthy, male volunteers (n=12) inhaled heliox (79% helium and 21% oxygen) and air. Blood sampling was done at T0 (baseline), T1 (25 min inhalation), T2, T3, T4 and T5 (1 h, 2 h, 6h and 24 h after inhalation respectively). C-reactive protein (CRP) was measured at T0 of each experimental cycle, leukocyte counts and differentials were analyzed at T0, T3 and T5 of each cycle. After sampling, whole blood was immediately incubated with (LPS) or with RPMI (as control, CON) for 2, 4 and 24 hours. TNF-alpha, IL-1beta, IL-6 and Il-8

levels were analyzed by cytometric bead array. Statistical analysis: Wilcoxon test for matched samples, all data are shown as mean ± SEM.

Results After 0, 2, 4 and 24 hours of incubation with LPS, the amount of TNF-alpha (see figure), Il-1beta, Il-6 and Il-8 (pg/ml) in whole blood was not affected by heliox inhalation in comparison to air at all timepoints. No differences in CRP, leukocyte counts and differentials were found between groups.

Conclusion A 30-minute episode of helium inhalation does not alter TNF-alpha, Il-1beta, Il-6 and Il-8 levels after incubation with LPS.

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oral presentations

Caption 1. Figure 1.


Reversion of high-fat diet normalizes myocardial function and sphingolipid levels in rats C.E. van den Brom1, R.A. Bouwman1, M.H. Graeler2, D.M. Ouwens3, M. Diamant1, C. Boer1 1 VU Medisch Centrum, AMSTERDAM, the Netherlands 2 Hannover Medical School, HANNOVER, Germany 3 German Diabetes Center, DüSSElDORf, Germany

Introduction The dietary balance between carbohydrates and lipids influences the ischemic tolerance and sevoflurane-induced cardioprotection in the rat heart. These findings suggest that alterations in dietary intake may improve the sensitivity of the heart to stress. As a first step, we explored the possible beneficial effects of reversal of high-fat diet-induced metabolic imbalance on myocardial function.

Methods Male Wistar rats (n=8 per group) were exposed to a high-fat (HFD) or control diet


(CD) for 8 weeks. A third group of HFDfed rats reversed after 4 weeks to CD for 4 consecutive weeks. Before sacrifice, rats underwent an oral glucose tolerance test and echocardiography. Myocardial function was evaluated by fractional shortening (FS), isovolumic relaxation time (IVRT) and E deceleration time (Edec). Left ventricular tissue was used for analysis of myocardial sphingolipid metabolism.

Results Compared to controls, HFD feeding was associated with impaired glucose tolerance, decreased myocardial systolic function (FS, -23%, p<0.05) and impaired early diastolic function (IVRT +43% and Edec +21%, both p<0.05). This was accompanied by decreased myocardial sphingolipid levels including C18-ceramide (-36%), sphingomyelin (-30%), phosphatidylcholine (-67%) and sphingosine (-18%) (all p<0.05). Reversion of HFD to CD resulted in normalization of

the glucose tolerance. Moreover, myocardial function improved as shown by increased FS (+12%, p<0.05) and shortened IVRT (-40%, p<0.05) and Edec (-11%, p<0.05) as compared to HFD-fed rats. This was accompanied by recovery of myocardial sphingolipid metabolism.

Conclusion HFD-induced metabolic alterations are associated with impaired myocardial sphingolipid metabolism and function, which could be normalized by a diet intervention. These results suggest that a dietary change may improve myocardial function. Further research is warranted to conclude on the effect of dietary changes on ischemic tolerance in diet-induced metabolic imbalance.

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abstracts 2010 oral presentat i o n

Effect of ketamine on endogenous pain modulation in healthy volunteers M. Niesters, E.Y. Sarton, A. Dahan LUMC, Leiden, the Netherlands

Inhibitory and facilitatory descending pathways, originating at higher central nervous system sites modulate activity of dorsal horn nociceptive neurons, and thereby influence pain perception. Diffuse Noxious Inhibitory Control (DNIC) and Offset Analgesia (OA) are two mechanisms involved in descending inhibition. Dysfunction of inhibitory pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain.

The authors previously showed that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine produces hyperalgesic responses to acute noxious experimental pain following the treatment period. The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control. Ten healthy subjects (4 men/6 women) received a 1-h placebo or S(+)ketamine (40 mg per 70 kg) infusion on two separate occasions in random order. Upon the termination of the infusion DNIC and OA responses were obtained. After placebo treatment significant descending

inhibition of pain responses was present for DNIC and OA. In contrast, after ketamine infusion, no DNIC was observed, but rather a significant facilitatory pain response (p < 0.01); the OA response remained unaffected. These findings indicate that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation and suggest that hyperalgesia following ketamine is associated with descending facilitatory modulation of spinal nociceptive responses. The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC.

posterdiscusso n

Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain M.J. Sigtermans, E. Olofsen, A. Dahan LUMC, Leiden, the Netherlands

Aims Pharmacological treatment of chronic (neuropathic) pain is often disappointing. In order to enhance our insight in the complex interaction between analgesic drug and chronic pain relief, we performed a pharmacokinetic-pharmacodynamic (PK-PD) modeling study on the effect of S(+)-ketamine on pain scores in Complex Regional Pain Syndrome type 1 (CRPS-1) patients.

Methods Sixty CRPS-1 patients were randomly allocated to received a 100-h infusion

of S(+)-ketamine or placebo. The drug infusion rate was slowly increased from 5 mg/h (per 70 kg) to 20 mg/h based upon the effect/side effect profile. Pain scores and drug blood samples were obtained during the treatment phase and pain scores were further obtained weekly for another 11 weeks. A population PK-PD model was developed to analyze the S(+)-ketaminepain data.

Results Plasma concentrations of S(+)-ketamine and its metabolite decreased rapidly upon the termination of S(+)-ketamine infusion. The chance for an analgesic effect from ketamine and placebo treatment was 70% and 20%, respectively. The pain data were well described by the PK-PD model with

parameters C50 = 10.5 ± 4.8 (population value ± SE) ng/ml (95% ci 4.37-21.2 ng/ml) and t½ for onset/offset = 10.9 ± 4.0 days (5.320.5 days).

Discussions Long-term S(+)-ketamine treatment is effective in causing pain relief in CRPS-1 patients with analgesia outlasting the treatment period by 50 days. These data suggest that ketamine initiated a cascade of events, including desensitization of excitatory receptor systems in the central nervous system, which persisted but slowly abated when ketamine molecules were no longer present.

posterdiscussi o n

Increased perioperative complications after major vascular surgery in patients with a preoperative abnormal exercise blood pressure response I. de Liefde, G.M.J.M. Welten, H.J.M Verhagen, R.T. van Domburg, R.J. Stolker, D. Poldermans Erasmus MC, Rotterdam, the Netherlands

Introduction Recent studies have shown that hypertensive or hypotensive blood pressure


response during a preoperative treadmill exercise test in patients with peripheral arterial disease (PAD) is associated with a two fold increased risk of cardiovascular events and mortality. However, it is unknown if these patients also experience an increased complication risk during major vascular surgery.

Methods Between 1993 and 2006, 665 consecutive PAD patients underwent elective major vascular surgery (carotid endarterectomy, abdominal aorta repair or lower extremity revascularization surgery) in the Erasmus MC.

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Hypertensive blood pressure response at the preoperative treadmill exercise test, was defined as a difference between the exercise systolic blood pressure and resting systolic blood pressure of more than 55mmHg. Hypotensive blood pressure response was defined as a drop in exercise systolic blood pressure below resting systolic blood pressure.

thrombectomy, re-operation and death) occurring within one month of the major vascular surgery were collected using medical records.

Perioperative complications (infection, myocardial infarction, angina pectoris, cardiac arrhythmia, heart failure, cerebrovascular accident or spinal cord ischemia, dialyses, amputation,

Results

Myocardial infarction, angina pectoris, heart failure, new cardiac arrhythmia’s and 30-day cardiac mortality together were classified as cardiac complications. Patients with a hypertensive blood pressure response during a preoperative exercise test (n=66) demonstrated a higher risk of thrombectomy (HR 2.80 95 %CI (1.24 - 6.33))

compared to patients with a normal blood pressure response (n=582). Patients with a hypotensive blood pressure response (n=18) showed an increased risk of myocardial infarction (HR 3.69 95 % CI (1.08 - 12.64)) and cardiac complications (HR 2.90 95 % CI (1.02-8.19).

Conclusion Patients with an abnormal blood pressure response have an increased risk of cardiovascular complications after elective major vascular surgery.

posterdiscussi o n

Pharmacokinetics of a highly concentrated intranasal midazolam spray in healthy adult volunteers A.A. Fiddelers1, N.M.L. Veldhorst1, P-H.M. Van der Kuy2, C. Neef1, M.A.E. Marcus1

Pharmacokinetic data (Cmax, Tmax, T1/2, AUC) were analysed using one-compartmental analysis.

1 Maastricht Universitair Medisch Centrum, Maastricht, the Netherlands 2 Orbis Medisch Centrum Sittard, Sittard, the Netherlands

Results Mean bioavailability of IN midazolam was 80%. Cmax of 82 ng/ml was reached 46 minutes after IN administration, and Cmax was found 105 ng/ml after IV administration. For IN administration, a T1/2 of 1.8 hours (SD 0.35) was calculated, compared to 2.2 hours (SD 0.41) after IV administration. Few side effects were experienced by the subjects.

Introduction Intranasally administered midazolam has been introduced as an alternative next to rectally administered diazepam for the acute treatment of epileptic seizures. In order to avoid first-pass elimination, a highly concentrated nosespray should be administered. The purpose of this study was to investigate pharmacokinetics and tolerability of midazolam in a new formulation, administered as a highly concentrated intranasal (IN) spray, compared with intravenous (IV) administration in healthy adult volunteers.

Methods Seven healthy volunteers were enrolled in a non-blind, randomised, crossover study. Subjects were given both IN and IV midazolam, with a washout period of at least five


Figure 1. Intravenous and intranasal midazolam

days between treatments. The newly developed IN midazolam formulation consisted of 5 mg midazolam base per 0.1 ml (one spray), and was once administered in one nostril. The IV midazolam solution (2.5 mg) was infused over 10 seconds. IV data were converted to 5.0 mg. Blood samples were taken before administration, and at regular intervals up to 240 minutes after dosing.

Conclusion A high concentration (60 ng/ml) was reached within 15 minutes after administration, which is comparable with results found in other studies. However, they found Tmax of 10-25 minutes, while in our study Tmax was 46 minutes. This is probably due to nasoral absorption. Furthermore, bioavailability after IN administration of midazolam was high, showing that a highly concentrated midazolam solution is a good alternative for other administration forms.

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Myocardial contrast echocardiography for the study of perioperative myocardial perfusion C.S.E. Bulte, J. Slikkerveer, O. Kamp, S.A. Loer, C. Boer, R.A. Bouwman VU medisch centrum, Amsterdam, the Netherlands

Introduction General anesthesia is associated with increased activity of the sympathetic autonomic nervous system, which may lead to alterations in myocardial blood flow (MBF). Historically, the lack of suitable intraoperative noninvasive imaging techniques prohibited investigation of the influence of general anesthesia on MBF in healthy subjects. Myocardial contrast echocardiography (MCE) is a recently developed noninvasive method for assessment of MBF. In this feasibility study of intraoperative MCE, we investigated the effect of sympathetic stimulation on MBF and the effect of general anesthesia on this relation.

Methods Five cardiovascular healthy men (age 3466 years) scheduled for general anesthesia were included. Integrity of cardiovascular autonomic control was confirmed using autonomic function tests. MCE was performed before and during the administration of 1.0 MAC sevoflurane and included MBF measurements at rest, during adenosine-induced hyperemia and in response to sympathetic stimulation by cold pressor testing (CPT). MCE provides an estimate of MBF expressed in intensity units per second (IU/s) by analysis of replenishment curves obtained during continuous contrast infusion. Flow reserve was calculated by MBFhyperemia/CPT/MBFrest. Data are given as mean±SD.

Results In the preoperative setting, basal MBF was 7.7±5.7 IU/s and increased to

16.4±5.1 IU/s during hyperemia and to 10.3±4.7 IU/s during CPT (both P<0.05). Intraoperatively, basal MBF was 8.4±5.2 IU/s, which was augmented to 21.4±14.2 IU/s during hyperemia (P=0.03) and to 15.0±10.5 IU/s during CPT (P=0.09). Alterations in MBF in response to stress and sympathetic stimulation were comparable for the preoperative and intraoperative measurements, indicated by flow reserves of 3.0±1.6 and 2.8±1.7 during hyperemia (P>0.05) and 1.7±0.7 and 1.9±0.9 during CPT (P>0.05).

Conclusion MBF measurements using MCE are feasible in the perioperative setting and provide a useful tool for studying the effect of general anesthesia on myocardial perfusion during hyperemia and increased sympathetic stimulation.

posterdiscussi o n

Prediction of early liver dysfunction after orthotopic liver transplantation using indocyanine green plasma disappearance rate J.J. Vos, T.W.L. Scheeren, J.K.G. Wietasch Universitair Medisch Centrum Groningen, Groningen, the Netherlands

Introduction Although the 1 and 5 year survival after orthotopic liver transplantation (OLT) has risen above 85% and 75%, respectively, morbidity and mortality is mainly determined in the early post-operative period. During this period, using physical examination and conventional laboratory findings, it is yet not easy to adequately assess initial graft function. Indocyanine Green Plasma Disappearance Rate (PDR-ICG) has been shown to predict early post-operative complications following OLT when measured during the first postoperative days.(1)(2) We evaluated the predictive role of intraoperative PDR-ICG values in the prediction of early post-operative complications after OLT.


Methods In this study, we retrospectively analyzed data from 62 patients undergoing OLT. Early post-operative complications were defined as the occurrence of primary non-function, hepatic artery or portal vein thrombosis, sepsis, need for surgical re-intervention, acute rejection or early ischemic biliary lesions. PDR-ICG was measured non-invasively by pulse dye densitometry at the end of surgery and was correlated with postoperative complications. ROC analysis was performed to determine the accuracy and optimal cut-off value for predicting early liver dysfunction.

%/min ± 8,2; p<0,05). ROC analysis revealed an area under the curve of 0,70 and a cut-off PDR-ICG value for predicting good early graft function was determined to be 23,9%/min with a sensitivity of 64,7% and a specificity of 72,7%. A further subgroup analysis could not determine specific complications to be predicted by intraoperative PDR-ICG measurements.

Conclusion Intraoperative measurement of PDR-ICG in OLT patients is a useful tool for prediction of early liver dysfunction.

Results PDR-ICG at the end of surgery was significantly lower in patients with than in patients without early post-operative complications (23,0 %/min ± 6,9 versus 27,2

references

1. Levesque E, et al. Liver Transpl 2009;15:1358-64 2. Olmedilla L, et al. Liver Transpl 2009;15:1247-53

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Safety of retransfusing shed blood after local infiltration analgesia in total knee arthroplasty B.J.W. Thomassen1, L.D. Pool2, R.E. van der Flier2, R.D. Stienstra3, B.A. in ‘t Veld4 1 MC Haaglanden, Den haag, the Netherlands 2 Afdeling Orthopedie, Medisch Centrum Haaglanden, Den haag, the Netherlands 3 Afdeling Anesthesiologie, St. Maartenskliniek, Nijmegen, the Netherlands 4 Afdeling Anesthesiologie, Medisch Centrum Haaglanden, Den haag, the Netherlands

Introduction High volume infiltration with local anaesthetics (LIA) during totalkneearthroplasty (TKA) for postoperative pain relief may be beneficial as compared to traditional methods. Retransfusion drains are used in TKA as alternative for allogeneic blood transfusions. When combining both modalities, recollected blood may contain large doses of local anaesthetics potentially leading to systemic toxicity during retransfusion. We investigated the safety of combining LIA and retransfusion of shed blood.

Methods Twenty patients scheduled for primary TKA were included. During surgery two peri-articular injections with ropivacaine (total 375 mg) were given. Patients received an intraarticular retransfusion drain and a wound catheter for continuous infusion of ropivacaine (8 mg/hr) for 24 hours. Blood collected in the retransfusion device, was not retransfused but used for laboratory analyses. Patients’ blood samples were taken immediately after surgery, 3, 6 and 24 hours postoperatively. We predicted cumulative ropivacaine concentrations using patient and shed blood data from 6 hours postoperatively. Assuming instant retransfusion we estimated cumulative plasma concentrations.

Results Total ropivacaine concentration was highest 24 hours postoperatively and unbound ropivacaine was maximal predominantly at 6 hours. Peak total ropivacaine

concentrations ranged from 684 to 1886 mcg/L and the unbound ropivacaine concentrations varied between 32 and 105 mcg/L. At 6 hours on average 591 mL shed blood was collected. Assuming retransfusion, on average 13 mg (6-18mg) of unbound ropivacaine would have been administered intravenously. The model used to estimate cumulative ropivacaine plasma levels showed that instant retransfusion would have led to plasma levels of below 0.6 mg/L.

Conclusion Under the conditions in our study it is safe to use LIA in combination with continuous infusion of ropivacaine. Moreover, it also appears safe to retransfuse blood collected with the Bellovac ABT system in combination with LIA and continuous infusion of ropivacaine through an indwelling catheter, although formal testing is required.

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Pain symptoms accompanying chronic post sternotomy pain, a cross-sectional cohort study N.J. van Leersum1, R.L. van Van Leersum2, H.F. Verwey3, R.J.M. Klautz3 1 MC Haaglanden, lok. Westeinde, Den haag, the Netherlands 2 Ziekenhuis Bronovo, Den haag, the Netherlands 3 LUMC, Leiden, the Netherlands

Instruction Despite the technical developments in surgical procedures, the incidence of chronic post-sternotomy pain (CPSP) is 30%. Many theories for its cause have been proposed in literature, but the etiology is still not clear. The incidence and etiology of painfull sites unrelated to the chest wall incision (neck, shoulder, arms, back) has been poorly evaluated and considered a separate complication. This exploratory study was designed to evaluate all pain symptoms accompanying CPSP after cardiac


surgery. Our hypothesis was that all pain symptoms post sternotomy were part of a united pain syndrome.

Methods A questionnaire was sent to 1097 patients that underwent sternotomy in the Leiden University medical centre. All patients that reported sternal pain and a random sample of patients without sternal pain were examined for pain of head, neck, back, chest and upper extremities. Pain symptoms in patients without sternal pain were contrasted with patients with sternal pain.

Results A 36% incidence of CPSP was reported in the questionnaire. In 277 patients, all pain locations were compared in two groups: 189 patients with

sternal pain and 88 patients without stermal pain. All patients with anamnestic paint, had a painful sternum on palpation. The incidence of pain of head (33%), neck (33%), shoulder (45%), between the scapulae (38%), chest wall (22%) and arms (21%) was high and significantly more common in patients with CPSP. No surgical or demographic factors, with exception of female gender, were consistent predictors of sternal pain.

Conclusion The results of this study show that CPSP is an extensive and complex pain syndrome which includes, alongside sternal pain, pain of the musculoskeletal components of the trunk, upper extremity, head and neck. In patients without a tender sternum, other pain symptoms were rarely seen.

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abstracts 2010 groep 1: pijn

A reinforced microglial response as as mechanism underlying long-term changes in paijn sensitivity after neonatal repetitive pain L. Knaepen1, R. Deumens1, D. Tibboel2, J. Patijn1, E.A.J. Joosten1

2. To investigate glial activation in the spinal cord as a possible underlying mechanism.

1 Maastricht University Medical Centre/ Anesthesiologie, Maastricht, the Netherlands 2 Erasmus-MC/Sophia Children’s Hospital, Rotterdam, the Netherlands

Methods

Introduction Neonates admitted to intensive care units and exposed to repetitive pain stimuli for diagnostic purposes, have long-term changes in pain sensitivity at baseline and in pathological conditions. Underlying mechanisms responsible for these changes are unknown. No experimental model mimicking both neonatal repetitive pain and adult inflammatory pain is currently available.

Objectives 1. To develop an animal model for neonatal repetitive pain exposure and its long-term pain sensitivity consequences.

Neonatal rat pups received four needle pricks per day during the first week of life into the left hind paw. Control rat pups received tactile stimuli. Eight weeks later all animals received an ipsilateral hind paw injection with complete Freund’s adjuvant (CFA), resulting in painful inflammation. Mechanical pain thresholds were measured weekly during development and 24h following CFA injection in the adult rat. Lumbar spinal cord sections were stained for microglial (Iba1) and astroglial (GFAP) activation. Relative proinflammatory cytokine (IL1β, TNFα and IL6) mRNA-concentrations were determined with RT-PCR.

Results Neonatal needle pricking did not result in

altered baseline thresholds to mechanical stimuli during development. Animals exposed to neonatal needle pricks showed increased pain sensitivity to mechanical stimuli following inflammation in adulthood. Microglial activation was apparent at the ipsilateral lumbar dorsal horn of these animals. Pro-inflammatory cytokine mRNAconcentrations did not differ between the groups.

Conclusion 1. Repetitive needle pricking in neonatal rats results in long-term consequences on inflammatory pain sensitivity, relating to clinical observations of increased pathological pain sensitivity in children which were exposed to neonatal pain. 2. Long-term changes in pain sensitivity following neonatal pain exposure might be related to altered microglial activation later in life.

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Translational research on central neuropathic pain and neuroinflamation after experimental spinal cord injury S.F.J. van Gorp1, E.A.J. Joosten2, P. Martínez-Martínez3, M. Losen3, M. de Baets3, M. van Kleef2, R. Deumens2 1 Maastricht University Medical Centre, Maastricht, the Netherlands 2 Maastricht University Medical Center, Maastricht, the Netherlands 3 Department of Neuroscience, Maastricht University, Maastricht, the Netherlands

Introduction Progression in therapeutic efficacy in Spinal Cord Injury (SCI) induced Central Neuropathic Pain (CNP) is hampered by lacunae in the comprehension of its pathophysiology. Importantly, SCI does not cause CNP per se, but, thus far, no predictors for CNP after SCI have been found. Data from animal studies indicate a role of specific neuroinflammatory processes in established CNP. However, it remains unknown (1) whether such neuroinflammatory processes are indeed differentially activated in CNP conditions


and (2) which molecular cues may predict CPN following SCI.

Objectives 1. To investigate whether an existing SCI animal model results in distinct CNP and non-CNP groups 2. To identify early neuroimmune-related predictors for the development of CNP (future plans)

Method Adult Sprague Dawley rats (200-220 grams) underwent either a moderate T9 spinal cord contusion injury (SCCI, n=19), a laminectomy (sham control, n=4), or no surgical procedure (naïve control, n=4). At baseline and early (two weeks) post-SCI mechanical nociceptive thresholds of the hindpaws were assessed with a dynamic plantar linear aesthesiometer. Two groups were assigned with the k-means clustering method based on the relative decreases of the hindpaw withdrawal responses.

Results The clustering method resulted in a CNP group (n=10), with a statistically significant decrease in nociceptive thresholds of 25.1% (SD±3.7%, P<0.01), and a non-CNP group (n=9), which remained at baseline values (+4.7%, SD±3.7%, P=0.30). Also, the control animals did not show any change in thresholds (-2.1% SD±6.8%, P=0.53), and between-group differences were only present between CNP vs. non-CNP and CNP vs. control animals (P<0.01 and P=0.01, respectively).

Conclusion A moderate T9-SCCI results in CNP and non-CNP rats. Therefore, analysis of the gene-expression in central nervous tissue from these animals can help defining specific (neuroinflammatory) molecular cues as predictors for CNP.

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Time-dependent plasticity of the spinal GABAergic system in relation to the degree of neuropathic pain S.P.M. Janssen1, M. Truin1, M. Van Kleef2, Elbert A. Joosten2

1 Maastricht University, Maastricht, The Netherlands 2 Maastricht University Medical Centre, Maastricht, The Netherlands

Introduction A decreased GABA inhibitory tone is known to contribute to a generalized state of neuropathic pain following peripheral neuropathy. Here we explore whether histological changes in the GABAergic system are related to the degree of mechanical allodynia in both acute and chronic neuropathic pain.

Methods Male Sprague Dawley rats were subjected to partial sciatic nerve injury and hind paw withdrawal thresholds to mechanical stimuli

were determined before and after injury. Dorsal horn laminae I-III of the L4-L5 spinal cords of animals with different degrees of mechanical allodynia (mild: 8.0-26.0 g (n=7) or moderate: 1,4-6.0 g (n=8)) were analyzed for GABA-immunoreactivity and the number of GABAergic cells at three (acute) or sixteen (chronic) days post-injury. Data (mean±SEM) were compared to sham-operated animals (n=8) unless stated differently.

Results No changes in GABA-immunoreactivity (89%±5% vs 100%±6%) or GABAergic cell numbers (44±3 vs 49±2) were observed in both acute mild and moderate allodynic rats. In contrast, GABA-immunoreactivity was increased in chronic neuropathic rats (119%±7% vs 100%±4%, p<0.05), without

differences between mild and moderate allodynic animals (115%±13% vs 122%±8%). The number of GABAergic cells did not change when comparing mild and moderate allodynic animals to controls (50±3 vs 48±3 vs 47±2). There was no correlation between both GABA-immunoreactivity or the number of GABAergic cells and the degree of mechanical allodynia.

Conclusion Our histological data do not suggest an important role of the GABAergic system during the acute phase of neuropathic pain. In contrast, chronic neuropathic pain coincides with increased dorsal horn GABA-immunoreactivity which is not due to alterations in the GABAergic cell number. Changes in the GABAergic system were not related to the degree of chronic neuropathic pain.

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Opioid chronopharmacology: influence of timing of infusion on fentanyl’s analgesic efficacy M.C.A. Boom1, J. Grefkens2, E.L.A. van Dorp1, E. Olofsen1, L.P.H.J. Aarts1, A. Dahan1, E.Y. Sarton1 1 LUMC, Leiden, the Netherlands 2 Rijnland Ziekenhuis, Leiderdorp, the Netherlands

measurements using a thermode placed on the skin were taken at regular intervals for 3-h and Verbal Analogue Scores (VAS) were then obtained. The data were modeled with a sinusoid function using the statistical package NONMEM.

Background

Results

Chronopharmacology studies the effect of the timing of drug administration on drug effect. Here we measured the influence of four timing moments on fentanyl-induced antinociception in healthy volunteers.

A significant circadian sinusoidal rhythm in the antinociceptive effect of fentanyl was observed. Variations were observed for peak analgesic effect, duration of effect and the occurrence of hyperalgesia. A peak in pain relief occurred late in the afternoon (5:30 PM) and a trough in the early morning hours (5:30 AM). The difference between the peak and trough in pain relief corresponds to a difference in VAS of 1.3 to 2 cm. Only when given at 2 AM did fentanyl cause a

Methods Eight subjects received 2.1 μg/kg intravenous fentanyl at 2 PM and 2 AM, with at least 2 weeks between occasions, eight others at 8 AM and 8 PM. Heat pain


small but significant period of hyperalgesia following analgesia. No significant changes were observed for baseline pain, sedation or the increase in end-tidal CO2.

Conclusions The variations in fentanyl’s antinociceptive behavior are well explained by a chronopharmacodynamic effect originating at the circadian clock in the hypothalamus. This may be a direct effect through shared pathways of the circadian and opioid systems or an indirect effect via diurnal variations in hormones or endogenous opioid peptides that rhythmically change the pain response and/or analgesic response to fentanyl.

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Intrathecal delivery of VEGF165 following experimental spinal cord injury results in modest attenuation of mechanical allodynia S.G.A. van Neerven, E.A.J. Joosten, R. Deumens

thermal hyperalgesia following spinal cord injury in the rat.

Maastricht Universitair Medisch Centrum, Maastricht, the Netherlands

Methods

Introduction Neurodegeneration and inflammatory responses in glial cells are thought to contribute to central pain following spinal cord injury. Neuroprotective therapies may therefore attenuate central pain by limiting tissue damage and inflammation. Vascular endothelial growth factor (VEGF) treatment has been shown to have neuroprotective effects following spinal cord injury, but effects on central pain remain unknown.

Female Sprague Dawley rats were subjected to spinal cord contusion injury (SCCI) at low thoracic (T9) level and received daily intrathecal bolus injections of VEGF165 for one week following injury (n=9) . Hindpaw withdrawal thresholds and latencies (for mechanical and thermal stimuli, respectively) were determined up to eight weeks post-injury. Tissues were processed for analysis of putative cellular and molecular mechanisms underlying the pain-related effects.

Objective

Results

Investigate the effect of early VEGF treatment on mechanical allodynia and

SCCI reduced both the hind paw withdrawal threshold to mechanical

stimulation and the withdrawal latency to thermal stimulation, which persisted for at least 2 months post-injury. Animals treated with VEGF165 showed a minor, but significant reduction in mechanical allodynia, but not thermal hyperalgesia. SCCI activates glia at lumbar levels, however this activation appeared unaffected in VEGF165 treated animals. At thoracic level, lesion size and glial scar formation remained unchanged; however VEGF165 induced neovascularisation at the lesion site.

Conclusion VEGF165 treatment after SCCI has small anti-allodynic effects. This behavioral effect could not be explained by changes in glial activation. However VEGF165 induced neovascularisation at thoracic levels, indicative of functionally active VEGF.

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Role of corticotropin-releasing factor and urocortin 1 systems in pain-induced maladaptation and comorbid diseases T.P.H. Rouwette1, W.J.J.M Scheenen2, E.W. Roubos2, T. Kozicz2, K.C. Vissers3

1 UMCN, Nijmegen, the Netherlands

2 Radboud Universiteit Nijmegen, Nijmegen, the Netherlands 3 Radboud Universiteit Nijmegen Medical Centre, Nijmegen, the Netherlands

Introduction Neuropathic pain patients have a high incidence of depression and anxiety and although the precise etiology of these painrelated mood alterations is not known, there is evidence for an involvement of the corticotropin-releasing factor (CRF) system. We hypothesize that neuropathic pain disrupts the homeostatic functioning of the CRF system of the hypothalamic paraventricular nucleus (PVN), the bed


nucleus of the stria terminalis (BST), the central amygdala (CeA), and the urocortin 1 (Ucn1) system of the non-preganglionic Edinger-Westphal nucleus (npEW), and consequently will trigger stress-related symptoms of depression and anxiety.

immunoreactivity in the CeA. There are no changes in CRF and CRF mRNA in the PVN. Also, the npEW does not differ in Ucn1 and Ucn1 mRNA. Corticosterone titers do not differ between shams and CCI-operated rats 24 days post-surgery.

Methods

Conclusion

Neuropathic pain is induced in rats by chronic constriction injury (CCI) of the sciatic nerve. Rats are tested for hyperalgesia/allodynia and anxiety/ depression. Brains are analyzed by quantitative immunohistochemistry and in situ hybridization.

Our results indicate that neuropathic painlike behavior in rats leads to a habituated stress response with persistent increases in CRF in the CeA and BST, possibly leading to symptoms of depression and anxiety. This is in clear contrast to acute pain stress induced bij injection of formalin into the hind paw, which activates the PVN and npEW, but not the CeA and BST. Taken together, our data show that acute and chronic pain comprise separate signaling cascades in different, stress-sensitive brain nuclei.

Results CCI leads to marked cold allodynia 24 days post-surgery and increased CRF mRNA in the CeA and BST and higher CRF-

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Decision support reduces PONV incidence in a general surgical population F.O. Kooij1, T. Klok2, M.W. Hollmann1, J.E. Kal2

1 Academisch Medisch Centrum, Amsterdam, the Netherlands 2 Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands

Introduction Guidelines to minimize the incidence of PONV have been implemented in many hospitals. In previous studies, we have demonstrated that guideline adherence is suboptimal and can be improved using decision support.1,2 In this study, we demonstrate that decision support not only improves physician behaviour, but also improves patient outcome.

Methods Medical information of surgical patients is routinely entered in our anesthesia

information management system (AIMS), which includes automated reminders for PONV management based on the simplified risk score by Apfel.3 This study included consecutive adult patients undergoing general aneshthesia for elective non-cardiac surgery which were treated according to normal clinical routine. The presence of PONV was recorded in the AIMS both during the recovery period and at 24 hours. Two periods were studied: one period without the use of decision support (control period) and one period with the use of decision support (support period). Decision support consisted of reminders on PONV both in the pre-operative screening clinic and at the time of general anesthesia.

Results In the control period 971 patients, of which

302 (31%) were high risk patients, received general anaesthesia. Overall 328 (34%) patients experienced PONV within 24 hours. In the support period 1750 patients, of which 575 (33%) had a high risk for PONV, received general anaesthesia. In this period, only 401 (22%) patients experienced PONV within 24 hours postoperatively.

Conclusion Automated reminders can improve patient outcome by improving guideline adherence.

references

1. Kooij et al, Anesthesia & Analgesia 2008 106(3):893 2. Kooij et al, European Journal of Anesthesia 2010 27(2):187 3. Apfel et al, British Journal of Anaesthesia 2002 88(2):234

groep 2: divers

Arterial and venous pharmacokinetics of morphine-6-glucuronide and impact of sample site on pharmacodynamic parameter estimates E.L.A. van Dorp1, E. E. Olofsen2, A. Dahan2, , 1 LUMC, Leiden, the Netherlands 2 Leids Universitair Medisch Centrum, Leiden, the Netherlands

Introduction In pharmacokinetic-pharmacodynamic modeling studies venous plasma samples are sometimes used to derive pharmacodynamic model parameters. In the current study the extent of arteriovenous concentration differences of morphine-6-glucuronide (M6G) was quantified. Simulations studies were applied to estimate possible biases in pharmacodynamic model parameters when linking venous versus arterial concen trations to effect.

Methods Seventeen healthy human volunteers received an intravenous 90-s infusion of 0.3 mg/kg M6G. Arterial and venous blood samples, from the radial artery and cubital vein, respectively, were obtained.


An extended pharmacokinetic model was constructed linking arterial and venous compartments. The extent of bias in pharmacodynamic model parameter estimates was explored in simulation studies with NONMEM, simulating M6G effect using first-order effect-compartment – inhibitory sigmoid EMAX models. M6G effect was simulated at various values for the arterial blood-effect-site equilibration halflifes (t1/2kE0), ranging from 5 to 240 min.

Results Arteriovenous concentration differences were apparent, with higher arterial plasma concentrations just after infusion while at later times (greater than 60 min) venous M6G concentrations exceeded arterial concentrations. The extended pharmacokinetic model adequately described the data and consisted of three arterial compartments, one central and one peripheral venous compartment. The simulation studies revealed large biases in model parameters derived from

venous concentration data. The biases were dependent on the value of t1/2kE0. Assuming that the true values of M6G t1/2kE0 range from 120-240 min (depending on the endpoint measured), we would have underestimated t1/2kE0 by 30%, while the potency parameter would have been overestimated by about 40%, when using venous plasma samples.

Conclusion Due to large arteriovenous differences in M6G plasma concentration, biases in pharmacodynamic model parameters will occur when linking venous concentration to effect, using a traditional effectcompartment model. In order to obtain optimal PD parameters for use in clinical practice, a pharmacodynamic model needs to be derived from arterial samples.

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Caption 1. Model in terms of volumes and clearances.

Caption 2. Model in terms of rate constants and compartments

groep 2: divers

Increased renal microvascular endothelial responsiveness to LPS in aged mice F.M. Wulfert, M. Meurs, van, N.F. Neng, R.M. Jongman, P. Heeringa, J.G. Zijlstra, M.M.R.F. Struijs, G. Molema UMCG, Groningen, the Netherlands

Introduction Incidence of acute kidney injury (AKI) following severe sepsis is higher in the elderly than in younger patients. We hypothesize that the microvascular endothelium is primed by ageing. Sepsis thus represents a “second hit”resulting in augmented responses causing more severe microvascular complications in the elderly. Interaction between activated neutrophils and endothelial cells is considered to play a role in the pathophysiology. We analyzed expression of adhesionmolecules and neutrophils in kidney in response to sepsis in young and aged mice

Methods 3 month and 18 month old female mice were i.p. injected with 1,500 endotoxinunits/gram lipopolysaccharide(LPS), and sacrificed after 8 hours. Neutrophil numbers in plasma were determined by flow cytometry. In kidney tissue we assessed neutrophil influx by immunohistochemical staining of Ly6G. qRT-PCR and immunohistochemistry were used to analyze mRNA and protein of E-selectin, and P-selectin.

Results The baseline neutrophil count was significantly lower in young compared to elderly mice (2.5 [SD 1.8] in 3 month versus 6.5 [SD 2.6] % in 18 month old mice), and the relative increase in response to LPS in neutrophil fraction was lower in young compared with aged mice (47.2

[SD 7.8] in 3 month versus 69.6 [SD 4.5] % in 18 month old mice). mRNA analysis showed significantly higher upregulation of P-selectin, and E-selectin 8 hours after LPS in kidney of elderly mice. Furthermore, increased neutrophil influx in LPS treated aged mice was observed.

Conclusion Aged mice showed an increase in circulating neutrophils. Furthermore, aged mice subjected to LPS showed increased renal influx of neutrophils, accompanied by an increased expression of adhesion molecules E-selectin and P-selectin. The higher neutrophil count, higher upregulation of adhesion molecules, and higher tissue influx of neutrophils in aged mice subjected to LPS may play a role in increased morbidity and mortality, which will be addressed in future studies.

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The effects of major and minor surgery on the tryptophan kynurenine pathway, neopterin and IL-6 J.W. Hol, R.J. Stolker, M. Klimek, F. van Lier, D. Stronks, D. Fekkes Erasmus MC, Rotterdam, the Netherlands

Background Anesthesia has wide ranging immuno modulatory properties of which the mechanism is poorly understood. In order to better understand the effect of surgery and anesthesia on inflammation, we designed a longitudinal observational study


investigating three inflammatory profiles of two separate patient groups undergoing surgery of differing severity while undergoing general anesthesia. In addition to measuring the well known inflammatory markers neopterin and IL-6, we also investigated the product of tryptophan, kynurenine.

female patients. Plasma levels of tryptophan, kynurenine, and IL-6 were determined from samples taken at: 24hrs pre-operative, prior to induction, thirty minutes before the operation was expected to end, and at 24 as well as 96 hours post operative in patients undergoing major abdominal surgery and vulvectomy.

Methods

Results

This study was a prospective, single center, two-armed observational study involving 28

15 and 13 patients were included in the vulvectomy and major abdominal

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surgery groups, respectively. In this study we show that anesthesia and surgery significantly increases the enzyme activity of indoleamine 2, 3 dioxygenase (IDO) as measured by the kynurenine/tryptophan ratio (P=0.003), while maintaining stable neopterin levels. However, major surgery causes a considerable IL-6 increase (P<0.001).

groep 2 Conclusion Anesthesia and surgery cause a significant tryptophan level decrease while significantly increasing IDO activity. Both types of surgery produce nearly identical neopterin time curve relationships, with no significant change occurring in either group. However, even though neopterin is unaffected by the severity of surgery, IL-6 responded

Caption 1. Plasma kynurenine levels and idoleamine activity

to surgical invasiveness by revealing a significant increase during major abdominal surgery. By comparing effects of two patient groups undergoing surgery of differing severity, these results provide evidence that anesthesia does not seem to be strictly immunosuppressive, but might have a buffering effect.

Caption 2. Peri-operative plasma neopterin levels

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Recovery discharge criteria after spinal anesthesia with articaine in day care surgery R.M. van Bockel1, E.W. van den Bosch2, M.M.R.F. Struys1, R.H.G van den Brom2 1 UMCG, GRONINGEN, the Netherlands 2 Medisch Centrum Leeuwaden, Leeuwarden, the Netherlands

Introduction Orthostatic hypotension as recovery discharge criterion after establishing the height of the sensory block is safe(1). However, current practice is to discharge


patients upon return of motor function. The presence of orthostatic hypotension in timerelation to return of motor function after spinal anesthesia with hyperbaric articaine was observed.

Methods 59 ASA I-II patients in daycare surgery who received spinal anesthesia with hyperbaric articaine 5% were included. Dosing was left to the individual anesthesiologist. Upon arrival in the recovery ward haemodynamics

were monitored and sensory block was evaluated. When the sensory block was below level T5, patients were placed in a sitting position for 5 min. This was repeated every 15 min until motor function recovered. Orthostatic hypotension was defined as a 10% drop in blood pressure with subjective symptoms.

Results Average surgery duration was 34.3 min. Upon arrival in the recovery ward median

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abstracts 2010 sensory block height was T7. 19 patients had a sensory block above T6. After 22.2 minutes this block progressed till below T6 and the patients were placed in a sitting position. None developed orthostatic hypotension. The remaining 40 were placed in a sitting position upon arrival in the recovery ward. 36 (61%) experienced no orthostatic hypotension, whereas postoperative return of motor function lasted 53.4 minutes. Four

patients had orthostatic hypotension with complaints. No orthostatic hypotension was observed in patients with sensory block below T5 15 minutes after arrival. The mean duration of the anesthesia until motor recovery was 94.9 minutes.

be achieved of if absence of orthostatic hypotension combined with a sensory block below T5 is used as discharge criteria.

Conclusion An average weighted reduction of recovery ward stay of 52 minutes (p<0.01) can

reference 1.

Knoerl(2001)

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Pulse Transit Time to assess the mechanism involved in CRPS-induced vasomotor dysfunction M.C. Kortekaas, S.P. Niehof, M.H.N. Van Velzen, R.J. Stolker, F.J.P.M. Huygen Erasmus MC, Rotterdam, the Netherlands

Introduction Complex Regional Pain Syndrome (CRPS) is a complication after surgery or trauma. In CRPS bloodflow can be altered due to vasomotor dysfunction (VMD). VMD can be caused by efferent (autonomous dysregulation) and/or afferent (endothelial dysfunction) mechanisms. It’s difficult to determine the involved mechanism. Therefore we need a reliable and objective method to assess the cause of VMD, allowing a mechanism based treatment. Pulse Transit Time (PTT) is the time between contraction of the heart (R-wave on ECG) and arrival of the resulting arterial pulse wave in the fingertips (photoplethysmography (PPG)) and reflects arterial compliance. By using temperature mediated vasomotor response (TMVR) and flow-mediated dilation (FMD), it should be possible to determine the underlying mechanism.

the efferent mechanism, a temperature (cold and heat) pain stimulus is applied. This evokes a vasoconstrictive TMVR. The afferent mechanism is tested with FMD by arterial occlusion of the upperlimb. The PTT change from baseline will be determined and recovertime to baseline.

(fig.1). In the CRPS-involved arm the PTT first decreases and recovers to baseline. In healthy volunteers PTT first increases and returns to baseline. CRPS-patients show a TMVR at a lower threshold in the involved arm.

Methods

Results

In this study 37 patients with CRPS (IASPcriteria) will be compared with age- and sexmatched healthy volunteers. Exclusion criteria are cardiovascular disease, diabetes and hematopoietic diseases. To measure

Preliminary results show no difference in PTT in healthy volunteers between both arms after TMVR and FMD. The PTT after FMD in the CRPS-involved arm is altered compared with healthy volunteers

Theoretically, PTT has potency as a diagnostic tool in CRPS with VMD. However, further research has to be performed before definite conclusions can be drawn.


Caption 1. Fig.1: PTT during FMD.

Conclusion

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Postoperative Urinary Retention: a biased diagnosis? L.S. Wagenaar1, J.K.G. Wietasch1, T.A. Brouwer2 1 UMCG, Groningen, the Netherlands 2 Medisch Centrum Leeuwarden, Leeuwarden, the Netherlands

Introduction Postoperative urinary retention (POUR) defined as the incidence of postoperative urinary catheterizations - remains one of the less well quantified medical problems associated with anaesthesia. The aim of this study was to identify the incidence of POUR after general and spinal anaesthesia in relation with the diagnostic criteria used by nursing staff.

Methods During a consecutive period of three months, 1765 adult surgical patients who did not receive an indwelling catheter perioperatively were included in the

study. Nursing staff reported all cases of catheterization following suspected POUR. Since a standardized protocol for diagnosing POUR was absent, nursing staff were free to choose their own diagnostic criteria (including discomfort and pain, palpation, percussion, time since operation, bladder volume measured by ultrasound). Patient data were collected after urinary catheterization. The internal validity was assessed by formation of a control group of 153 randomly selected surgical patients who met the in- and exclusion criteria.

Results The incidence of POUR was significantly higher after spinal anaesthesia (8.6%) compared to general anaesthesia (5.6%, Chi-square, p=0.01). Ultrasound scanning as a sole diagnostic criterion was significantly more often used after spinal anaesthesia

than after general anaesthesia (62% vs 28%). Also, after spinal anaesthesia, patients were catheterised significantly earlier as compared with general anaesthesia (mean 180 (range 160 - 270) min and 385 (327-473) min, respectively). However, urine volumes measured at catheterisation were similar among both these groups: 669 ± 211 ml and 702 ± 270 ml (mean ± SD).

Conclusion In this study, spinal anaesthesia leads to a higher incidence of POUR and earlier urinary catheterizations as compared to general anaesthesia. This can be explained by a different diagnostic strategy used by nursing staff, but also by a possible difference in aetiology for development of POUR between spinal and general anaesthesia.

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Endotracheal intubation using videolaryngoscopy causes less cardiovascular responses compared to classic direct laryngoscopy R.L.J.G. Maassen1, B. Pieters2, B. Maathuis3, J. Serroyen4, M.A.E. Marcus2, A.A.J. Van Zundert5 1 MUMC+/ Catharina Ziekenhuis Eindhoven, Roosteren, the Netherlands 2 MUMC+, Maastricht, the Netherlands 3 Department of Biomechanical Engineering, Technical University, Delft, the Netherlands 4 Department of Methodology and Statistics. Maastricht University, Maastricht, the Netherlands 5 Catharina Ziekenhuis, Eindhoven, the Netherlands

Introduction Cardiovascular responses to endotracheal intubation have been well documented for direct laryngoscopy. Previous studies, comparing the Glidescope® and classic direct laryngoscopy, were not able to show an attenuation of cardiovascular responses to endotracheal intubation. We hypothesized that cardiovascular responses to endotracheal intubation using less traumatic, indirect videolaryngoscopy -- incorporating a Macintosh blade -- are diminished compared to direct classic laryngoscopy.


Methods In a randomized cross-over study, eighty consecutive adults (ASA PS II-III) scheduled for elective surgeries requiring endotracheal intubation and intra-arterial blood-pressure monitoring, were included and given standardized anesthesia. Both direct and indirect videolaryngoscopies were used in a random order, in the same patient. Measurements were taken during the first endotracheal intubation, without inflating the cuff. Subsequently, the ETT was withdrawn followed by a 3-min washout period. The follow-up measurements were taken at one and three minutes after withdrawal of the first ETT and new baseline hemodynamic values were obtained. Then, the second endotracheal intubation was carried out, including inflation of the cuff, followed by identical hemodynamic measurements. Cardiovascular responses to intubation were recorded as a relative change in rate pressure product (RPP = systolic blood pressure times heart rate) from baseline

values. Statistics were performed using a linear mixed model in Statistical Analysis Software (SAS®), SAS inc. version 9.2, 2008.

Results The relative increase of the RPP at intubation was significantly less (i.e. 24%, P<0.001) using videolaryngoscopy compared to classic direct laryngoscopy. Even after correction for beta-blocker use, statistically significant cardiovascular responses (P<0.001) could be recorded at intubation, with diminished responses (on average 12%) in the beta-blocker group.

Conclusions Our study shows less hemodynamic responses during endotracheal intubation using indirect videolaryngoscopy incorporating a Macintosh blade compared to classic direct laryngoscopy.

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Withdrawal of low dose aprotinin from anti-fibrinolytic therapy with tranexamic acid is associated with increased blood loss and transfusion requirements in cardiothoracic surgery M.I. Meesters, A.B.A. Vonk, J.W.A. Romijn, E.K. Jansen, C. Boer VU medisch centrum, Amsterdam, the Netherlands

Background This retrospective evaluation investigated whether withdrawal of low dose aprotinin from standard anti-fibrinolytic therapy with tranexamic acid (TXA) has led to alterations in postoperative blood loss and outcome in patients undergoing cardiothoracic surgery.

Methods Cardiothoracic surgery employing cardiopulmonary bypass (CPB) was performed in patients receiving a combination of 2000 mg TXA with low dose aprotinin (2*106 IU; n=615) or

patients receiving TXA only (n=587). Study endpoints were postoperative blood loss, transfusion requirements, rethoracotomy, glomerular filtration rate (GFR) and mortality.

Results There was no difference in age, comorbidity, cardiac function, Euroscore, type of surgery, CPB time, antiangial medication and baseline hemoglobin, activated partial thromboplastin time (aPTT) or prothrombin time (PT) between groups. The TXA group included more males (85%) than the TXA+aprotinin group (77%; P=0.02). Postoperative blood loss (0.80±0.69 vs. 0.66±0.52 liter; P=0.001) and transfusion of fresh frozen plasma (0.6±0.7 vs. 0.4±0.6 units; P<0.001), packed cells (3.9±5.5 vs.

2.7±3.3 units; P<0.001) and platelets (0.7±0.6 vs. 0.5±0.6 units; P<0.001) was higher in the TXA group than in patients receiving TXA with low dose aprotinin, respectively. There were more rethoracotomies in the TXA group (53 vs 34, respectively; P=0.03). Mortality was similar. Although baseline GFR was higher in TXA patients (79±31 vs. 68±24 mL/min/1,73m²; P<0.001), the perioperative deterioration of GFR was higher in the TXA group (P=0.02).

Conclusion Withdrawal of low dose aprotinin from standard tranexamic acid anti-fibrinolytic therapy is associated with increased blood loss, transfusion requirements and rethoracotomies without profound effects on renal function and mortality.

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Comparison of non-invasive continuous arterial waveform analysis (Nexfin HD) with transthoracic Doppler echocardiography for monitoring of cardiac output A.G.E. van der Spoel1, R.A. Bouwman1, A.C. Folkers2, A.J. Voogel2, C. Boer1 1 VU Medisch Centrum, Amsterdam, the Netherlands 2 Spaarne Ziekenhuis, Hoofddorp, the Netherlands

Introduction Non-invasive methods for cardiac output monitoring have become increasingly important to avoid the risk of invasive techniques. The Nexfin HD monitor uses the volume-clamp method and computes cardiac output (CO) from continuous brachial artery blood pressure waveforms. In this study, we compared the CO derived from beat-to-beat non-invasive blood pressure measurements using Nexfin with the CO obtained from transthoracic


Doppler echocardiography (TTE).

Methods In 40 patients scheduled for routine TTE examination CO was simultaneously measured with Doppler ultrasound and derived from Nexfin HD (BMEYE, Amsterdam, the Netherlands) blood pressure measurements. Correlation and level of agreement between Nexfin and TTE were analyzed using Pearson correlation coefficient and Bland-Altman plots.

Results

a bias of 0.51 ± 1.1 L/min and limits of agreement of -1.6 - 2.6 L/min with a percen tage error of 39%.

Conclusion Considering limits of precision of CO measu rements with Doppler echocardiography (±30%), our data show that the agreement between non-invasive cardiac output measurement with the Nexfin and TTE is reasonable. These results may suggest clinical applicability of Nexfin CO measurements and warrant validation in more diverse patients groups under various clinical conditions.

The Pearson correlation coefficient for Nexfin versus TTE was 0.68 (CI: 0.46 - 0.82, P < 0.0001). Bland-Altman analysis revealed

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Does pneumatic tube transport influence TEG and ROTEM thromboelastography/-metry? M.C. Timmerman, R. Van Oerle, Y.M.C. Henskens, M.A.E. Marcus, M.D. Lancé MUMC, MAASTRICHT, the Netherlands

Introduction Point-of-care monitoring is increasingly used in modern anesthesiology. Reproducibility of new assays needs to be evaluated with respect to pre-analytical conditions. A pneumatic tube system (PTS) can cause hemolysis and unknown changes on coagulation by rapid acceleration and deceleration. Effects of a PTS on TEG and ROTEM are unknown. Aim of this study was to evaluate the influence of PTS transport on TEG and ROTEM results.

Methods After institutional approval and written informed consent two citrated blood samples were collected pre-operatively from seventeen patients scheduled for

Caption 1. Tabel 1. ‘Clotting time for TEG and Rotem’

elective cardiac surgery. One sample was transported to the central laboratory by walking; another was transported by a PTS (ErgoTrans). This PTS generates a maximum speed of 8 m/s. At the central lab both specimens were analyzed by TEG and ROTEM with standard reagents following manufacturers recommendations. Statistical analysis was performed by SPSS 15 using student´s t-test and Wilcoxon signed ranks analysis.

Results Coagulation profiles of blood transported walking or by PTS (ROTEM vs TEG)

showed similar values for ‘angle’ and ‘clotting strength’. With TEG ‘clotting time’ was significantly lower when transported by PTS. Also with ROTEM ‘clotting time’ tended to be lower when transported by PTS. This was not statistically significant.

Conclusion Pneumatic tube transport significantly only shortens TEG-clotting time and not ROTEM-clotting time. Other variables measured by TEG and ROTEM are unaffected by this PTS.


Blood volume measurements by contrast enhanced ultrasound and thermodilution: an in vitro comparison

Caption 1. Figure 1: Correlation BV measurement by thermodilution and contrast enhanced ultrasonography

E.H.A. Maas1, I.H.F. Herold2, M.P.J. Kuenen3, A.J.G.H. Bindels2, M. Mischi3, H.H.M. Korsten2 1 MUMC+, MAASTRICHT, the Netherlands 2 Catharina Ziekenhuis, Eindhoven, the Netherlands 3 TU Eindhoven, Eindhoven, the Netherlands

Introduction In clinical practice, blood volumes (BVs) are typically measured by thermodilution.


Caption 2. Figure 2: Bland Altman

Recently, Contrast Enhanced UltraSound (CEUS) has been proposed as an alternative for BV assessment. BV assessment by CEUS involves measurement of flow and analysis of Ultrasound Contrast Agent (UCA) Indicator Dilution Curves (IDCs) for the estimation of UCA Mean Transit Time (MTT). In this work we compare BV measurements by thermodilution and CEUS in vitro.

Methods The model consisted of a centrifugal pump and a variable network with an inflow and outflow cannula. SonoVue® UCA (1 mg in 20 ml saline at 4°C) was injected right after the pump. The UCA passage through the inflow and outflow cannulas was measured simultaneously by an ultrasound transducer and a thermistor (PICCO),

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abstracts 2010 producing two UCA and thermodilution IDCs, respectively. After estimation of the UCA and thermic MTT from the UCA and thermodilution IDCs, the network volumes were estimated by each technique as the product between flow (measured by an electromagnetic flowmeter) and MTT difference. All measurements were repeated at different flows and volumes and compared with the real volumes.

Results

Conclusion

The determination coefficient R2 between CEUS and PICCO BVs was 0.91 (Fig.1). Comparison of CEUS and PICCO BVs with the real volumes provided a R2=0.90 and R2=0.94, and a bias of -212 ml and +94 ml, respectively. Comparison of the two techniques by Bland Altman analysis is shown in Fig.2.

CEUS is a valid minimally invasive option for BV assessment. It provides good correlation with real volumes determined in vitro. Bland Altman analysis showed significant bias between the two techniques, which might be explained by heat dispersion outside the tubes. Further investigation is however necessary.


Perioperatieve prohormone levels of atrial natriuretic peptide, adrenomedullin and vasopressin during cardiac surgery: an explorative study K.W.L. van Deutekom, A.B.A. Vonk, R.A. Bouwman, S.A. Loer, C. Boer VUMC, Amsterdam, the Netherlands

we investigated whether an increase in the classical inflammation marker IL-6 is paralleled by increases in pro-ANP, pro-ADM and copeptin in cardiac surgery.

Introduction

Methods

Coronary artery bypass grafting (CABG) in combination with cardiopulmonary bypass (CPB) is associated with the induction of inflammatory responses that may impair postoperative recovery and myocardial function. The molecular identification of postoperative cardiac dysfunction is usually restricted to the evaluation of ischemic markers like CK-MB and troponin. Until now, there is limited data available about the course of the prohormones atrial natriuretic peptide (pro-ANP), adrenomedullin (proADM) and vasopressin (copeptin) as novel biomarkers for cardiovascular stress. Here

Plasma samples of 30 patients undergoing CABG were obtained before (baseline) CPB, after CPB (post-CBP) and at the intensive care unit (ICU). IL-6 was measured by ELISA, whereas pro-ANP, pro-ADM and copeptin levels were determined with TRACE technology at a Kryptor compact device (Brahms, Germany).

Results IL-6 levels increased from 14.6±1.9 (baseline) to 56.2±5.9 pg/ml and 120.1±14.1 pg/ml (post-CPB and ICU, respectively; p<0.05 vs. baseline). CPB was associated with an

increase in post-CPB and ICU levels of proANP (260.1±23.7 and 203.9±21.9 pmol/l, respectively) as compared to baseline (129.8 ± 14.5 pmol/l; both p<0.05 vs. baseline). Similar findings were obtained for pro-ADM which increased from 0.66±0.03 pmol/l to 1.15±0.08 and 1.34±0.12 pmol/l at post-CPB and ICU, respectively (both p<0.05 vs. baseline). In contrast, copeptin levels showed a transient increase from 12.1±1.3 pmol/l to 117.2±18.3 pmol/l and subsequently decreased to 70.0±10.9 pmol/l during ICU stay.

Conclusion Perioperative increases in IL-6 are paralleled by elevation of pro-ANP and pro-ADM, whereas copeptin is transiently elevated during cardiac surgery. Future studies should elaborate the predictive value of novel biomarkers for cardiac stress after surgery.


Development of phosphorescent nanovesicles for measuring microvascular PO2 S.I.A. Bodmer1, M. Heger2, M. Broekgaarden3, T. Johannes4, D. Gommers5, R.J. Stolker4, E.G. Mik4 1 ErasmusMC, Rotterdam, the Netherlands 2 Department of Experimental Surgery, AMC, Amsterdam, the Netherlands 3 Institute of Biomembranes, University of Utrecht, Utrecht, the Netherlands 4 Department of Anesthesiology, ErasmusMC, Rotterdam, the Netherlands 5 Department of Intensive Care, ErasmusMC, Rotterdam, the Netherlands

Introduction Current phosphorescence-based microvascular PO2 (μPO2) measurements rely on injected soluble phosphorescent


compounds bound to albumin to ensure compartmentalization within the circulation. Albumin extravasation and turnover during long lasting experiments, or enhanced vascular leakage (e.g. sepsis), pose constraints on the clear definition of the measurement compartment. A recently developed in vivo mitochondrial PO2 (mitoPO2) measurement method and the prospects of simultaneous μPO2 and mitoPO2 monitoring urge the need to improve the μPO2 technique. We researched the feasibility of encapsulating phosphorescent dyes in the membrane of liposomes in order to construct oxygendependent phosphorescent nano-vesicles (PNVs).

Methods For a first proof of concept we constructed PNVs with a diameter of 400nm containing 10μM Pd-meso-tetra(4carboxyphenyl)-porphyrin (Pd-porphyrin, a “classic”phosphorescent compound used for μPO2 measurements). PNVs were synthesized out of 1,2-distearoyl-sn-glycero3-phosphatidylcholine (DSPC) (Avanti Polar Lipids, Alabaster, AL) and 1,2-distearoylsn-glycero-3-phosphatidylethanolaminepolyethylene glycol 2000 (DSPE-PEG) (Sigma Aldrich, St.Louis, MO). Pdporphyrin was purchased from Porphyrin Products (Logan, UT). Improved PNVs were developed by synthesizing stable 200nm DSPE-PEG vesicles containing

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membrane bound Pd(II)meso-cis-di(Nmethyl-4-pyridyl)diphenyl-porphyrin (PdPporphyrin).

Results Liposomes synthesized in the presence of Pd-porphyrin clearly showed absorption and emission spectra similar to the porphyrin, indicating successful incorporation of Pd-porphyrin into the membrane. Moreover, oxygen-dependency

groep 3 of the phosphorescence emission was readily detectable. However, large residues of unincapsulated Pd-porphyrin after liposome extrusion were present; incorporation was perfected using PdP-porphyrin which enhanced phosphorescence emission. The in vitro stability and homogeneity of the PNVs was kept within close margins.

Conclusion PdP-porphyrin containing PNVs were

developed with enhanced phosphorescence emission and good in vitro stability and homogeneity. Currently the oxygendependence of phosphorescence emission is being characterized. In the near future we will test the PNVs in vivo determining biostability and subsequently in vivo μPO2 sensitivity. Acknowledgements: This research was supported by the NVA Young Investigator Grant 2009.


Helium induced early and late preconditioning in human endothelium K.F. Smit, G.T.M.L. Oei, N.C. Weber, E.S. Stroes, M.W. Hollmann, B. Preckel AMC, AMSTERDAM, the Netherlands

Instruction Ischemic or anesthetic preconditioning protects human endothelium against Ischemia/Reperfusion (I/R) injury in healthy volunteers. Experimental data show the non-anesthetic noble gas helium induces preconditioning and attenuates infarct size after coronary occlusion in rats1,2. We hypothesised that helium inhalation induces

preconditioning in human endothelium in vivo, thereby attenuating endothelial dysfunction after I/R in the human forearm.

Methods With ethical approval, 50 healthy volunteers were randomised to five groups; except for controls, volunteers underwent 20 min forearm ischemia followed by 15 min of reperfusion in the absence (I/R group) or presence of helium inhalation (3*5 min; mixture of 79% helium, 21% oxygen) either 15 min (He-EPC) or 24 hours (He-LPC) before forearm ischemia. Another group

received 3 x 5 min ischemic preconditioning and served as positive control (IPC). Endothelial function was measured by venous occlusion plethysmography and endothelium-dependent vasodilatation was determined by intra-brachial infusion of acetylcholine (0.1-5.0g/100mlFAV/min) before and after ischemia, respectively.

Results I/R of the forearm induced endothelial dysfunction and resulted in a blunted dose response curve to acetylcholine (P= 0.001). He-EPC improved postischemic

Caption 1. acetylcholine dose response curve


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abstracts 2010 endothelial function and preserved response curve to acetylcholine (P=0,581). Even when administered 24 hours before I/R, He-LPC was able to improve postischemic endothelial function (P=0,165). This protection is comparable to protection elicited by IPC.

Conclusion These data show for the first time that helium induces early and late preconditioning in humans. Helium preconditioning showed to be as effective as ischemic preconditioning in protecting from I/R damage in this human forearm model.

references

1. Huhn, R., et al. Br J Anaesth. 102.5 (2009). 2. Pagel, P. S., et al. Anesth Analg. 105.3 (2007) supported by a CSRA of the IARS to B.P.

groep 4: divers

Effects of helium on H2O2 induced damage in HUVEC D. van de Vondervoort, K.F. Smit, M.W. Hollmann, B. Preckel, N.C. Weber AMC, Amsterdam, the Netherlands

Introduction Helium induces preconditioning in human endothelium in vivo. We used Human umbilical vein endothelial cells (HUVEC) to investigate the endothelium in vitro. We know that the noble gas xenon protects HUVEC against TNF- induced damage , and that propofol protects from H2O2 induced damage by suppressing Caspase 3 activity . We hypothesised that pretreatment with helium might protect the endothelium against H2O2 induced apoptosis.

Methods HUVEC were isolated from fresh umbilical cords and passaged upon confluency. Cells were given resting medium (M199, 10%FCS,

Pen/Strep, Amfo, L-glutamine) without addition of growth factors, 10hrs before start of experiment which were performed thrice. Cells were treated 3 x 5 min with Helium (5% CO2, 25% O2, 70% Helium) or control gas (5% CO2, 25% O2, 70% N2) at 37ºC in a gas chamber, medium was refreshed after the stimulus to assure washout. After treatment cells were either stimulated with H2O2 (100μM, 1.5 hours) or left untreated. Both adherent and detached cells were harvested for FACS analysis of Annexin V (AnV) and Propidium Iodide (PI).

Results Stimulation with H2O2 induced damage demonstrated by an increase of detached cells in both control gas- (32.1%±23.1) and helium pre-treated cells (25.9%±22.2), without statistically significant difference between groups. Pretreatment with helium

alone did not influence the amount of detached cells (1.0%±1.2) compared to controls (0.9%±0.5). AnV staining showed H2O2 induced apoptosis in both control and helium pretreated cells (50.8%±34.0 vs. 48.1%±37.1.p=0.93). PI staining revealed 94.4%±5.7 of the H2O2 stimulated cells and 97.5%±0.5 of the Helium pretreated cells were positive for PI, indicating either late apoptosis or direct necrosis.

Conclusion H2O2 (100 μM) induces detachment of endothelial cells, and cell death of adherent cells either by apoptosis (50%) or necrosis. Helium pretreatment had no effect on H2O2 induced cell damage, and helium treatment alone does not induce apoptosis or necrosis.

groep 4: divers

Ultrasound assistance for positioning of epidural catheters in neonates and infants M.F. Grapenthin, A.R. Absalom, J.K.G. Wietasch, R.J. Steur UMCG, GRONINGEN, the Netherlands

Introduction In young children, especially neonates, it is difficult to detect the epidural space with the loss of resistance (LOR) technique. Ultrasonography may assist epidural cannulation by demonstrating anatomic structures and verifying correct catheter placement.


Here we report the results of a comparison of clinical measurement of the depth until LOR with ultrasonic measurement of the distance between skin and dura.

Methods Pediatric patients scheduled for major abdominal surgery with planned epidural analgesia were included during a period of 16 months. After induction of anesthesia, ultrasound was used to identify the midline and the epidural space, and to measure the distance from skin to dura. Thereafter the epidural

catheter was inserted using the standard LOR technique and the depth at which LOR occurred was noted. When the epidural test bolus was administered, ultrasound was used to verify the position of the catheter tip. The two methods of depth measurement were compared using Bland- Altman analysis.

Results Five lumbosacral and 20 thoracic epidural catheters were placed in 25 patients with median (range) age 74 days (2 - 335) and weight 3.7 kg (1.6 - 10.2). In all patients the midline and dura were readily identified. The skin - dura distance with ultrasound

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technique was 6 mm (4-8) and 6.5 mm (5-9) with the LOR technique. The correlation coefficient between the measurements was 0.79. The Bland-Altman analysis of ultrasound vs. LOR showed good agreement with a bias of -0.6 mm and a precision of 1.5 mm.

groep 4 Conclusion This investigation shows that ultrasound assistance during placement of epidural catheters in neonates and infants can help to identify the relevant structures and gives a reliable indication of the depth of

the epidural space. This helps to improve safety in a normally “blindly”performed procedure.

groep 4: divers

Crystalloid Fluid restriction during pancreatic surgery has no measurable effect on delayed gastric emptying : the results of a doubleblinded prospective trial (EPOR) G. van Samkar, O.R.C. Busch, R.J. Bennink, W.J. Eshuis, T.M. Van Gulik, M.G.W. Dijkgraaf, B. Preckel, S.G. De Hert, D.J. Gouma, M.W. Hollmann AMC, Amsterdam, the Netherlands

Introduction A number of recent studies have shown beneficial effects of perioperative fluid restriction during intra-abdominal surgery on various outcome parameters including complications, recovery of gastrointestinal function and duration of hospital stay. Our aim was to investigate whether intraoperative crystalloid fluid restriction in pancreatic surgery would be beneficial. The main endpoint was delayed gastric emptying (DGE), measured 7 days postoperatively by Technetium scan.

Methods The study was approved by the Ethics board. After written informed consent, 66 patients were randomized, and 50 patients completed the full protocol. 26 patients were subjected to a restricted (R) fluid protocol (5ml/kg/hr) and 24 patients to a standard (S) fluid protocol (10ml/kg/ hr) during the operation. Postoperative fluid was set at 2.5 liters / 24h in both groups. 33 pancreatoduodenectomies (PD) and 17 double bypass (DBP) operations were performed. All patients underwent preoperative and postoperative gastric emptying scintigraphy.


Caption 1. Trial profile

Results DGE occurred in 12 out of 26 patients in the R group and in 11 out of 24 patients in the S group. The time to empty half of the stomach contents (T½) was 194 min (CI 95% 133 - 254) in the S group, and 170 min (CI 95% 110 - 222) in the R group, with a P value of 0.543 (NS). Complications, weight gain and duration

of hospital stay were comparable in both groups.

Conclusion Our results do not support the hypothesis of a beneficial effect of crystalloid fluid restriction during pancreatic surgery on DGE incidence or clinical outcome.

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abstracts 2010

Caption 2. Results

groep 4: divers

A Macintosh laryngoscope blade for videolaryngoscopy reduces stylet use in patients with normal airways R.J. Willems1, A. Van Zundert2, R. Maassen1, R. Lee3

1 AZM, MAASTRICHT, the Netherlands 2 Catharina Ziekenhuis, EINDHOVEN, the Netherlands 3 Technische Universiteit, DElfT, the Netherlands

Introduction Recently, complications have been reported associated with the use of styletted tracheal tubes in combination with videolaryngoscopy. In this study, a comparison was made between three videolaryngoscopes (VLSs): the GlideScope® Ranger[TRADEMARK], the V-MAC[TRADEMARK] Storz® Berci DCI®, and the McGrath® and we tested whether it was feasible to intubate the trachea of patients with videolaryngoscopy without using a stylet.


Methods 450 adults undergoing tracheal intubation for elective surgery were randomly allocated for airway management with one of the three devices. An independent anesthesiologist scored the CormackLehande laryngoscopy grade, after which the trachea was intubated using one of the VLSs. During intubation, the following data were collected: intubation time, number of intubation attempts, use of extra tools to facilitate intubation, and overall satisfaction score of the intubation conditions.

Results All three VLSs offered equal or better view of the glottis as assessed by the mean Cormack-Lehane grade, compared with the traditional Macintosh laryngoscopy. Intubation with the Storz was faster than the other two VLS tested and necessitated fewer additional tools, resulting in a higher

first-pass successful intubation rate. A stylet had to be used in 7% of the patients in the Storz group versus about 50% of the patients when the other two VLS were used.

Conclusion A large proportion of patients with normal airways can be intubated successfully with certain VLS blades without using a stylet, although the three studied VLSs clearly differ in outcome. The Storz VLS displaces soft tissues in the fashion of a classic Macintosh scope, affording more room for tracheal tube insertion and limiting the need for stylet use compared with the other two scopes.

10-09-10 12:03

2010 N

Advertentie

ADVERTORIAL

Bridion® (sugammadex) in de praktijk bij Ludo Coenen, anesthesioloog Gelre Ziekenhuis in Apeldoorn:

“De pulmonaal belaste patiënt belicht”

Het is bekend dat de pulmonaal belaste patiënt een verhoogd risico heeft op postoperatieve pulmonale complicaties. Daarom heeft de Stuurgroep Zichtbare Zorg voor de pulmonaal belaste patiënt in de set externe kwaliteitsindicatoren aangeraden de pulmonaal belaste patiënt preoperatief als risicopatiënt aan te merken3. In de indicatoren set wordt de pulmonaal belaste patiënt als zodanig aangemerkt als er sprake is van, in onderstaande de tabel genoemde, operatie en/of patiënt gerelateerde risicofactoren. OperatIegerelateerDe patIëntgerelateerDe rISIcOfactOren rISIcOfactOren • abdominale chirurgie • (met name aortachirurgie) • • thoraxchirurgie • • neurochirurgie • • hoofd/halschirurgie • • perifere vaatchirurgie of: • • geplande operatieduur >2,5 uur • peroperatieve bloedtransfusie > 4 packed cells

leeftijd (> 60 jaar) cOpD instabiel astma hartfalen slechte functionele status (totale of partiële afhankelijkheid) laag albuminegehalte (< 39 g/l)

er wordt aangegeven dat, door een betere peri-operatieve behandeling, het aantal postoperatieve pulmonale complicaties kan afnemen3.

Welke rol kan Bridion in dit geheel spelen? Deze vraag werd gesteld aan anesthesioloog ludo coenen uit het gelre Ziekenhuis te apeldoorn postoperatieve pulmonale complicaties komen inderdaad frequent voor en leveren een belangrijke bijdrage aan het operatierisico4. Ook hiervoor geldt voorkomen is beter dan genezen. De start maken we op de preoperatieve polikliniek, waar risicofactoren die kunnen bijdragen aan peri-operatieve complicaties (dus ook pulmonale postoperatieve complicaties) worden gesignaleerd en gedocumenteerd. preoperatief kunnen we dan al maatregelen treffen om het risico zoveel mogelijk te verkleinen. peroperatief gebruiken we, indien mogelijk, bij de pulmonaal gecompromitteerde patiënt bij voorkeur een neuraxiale blokkade. De patiënten die geïntubeerd worden krijgen zoveel mogelijk ook een vorm van locoregionale anesthesie omdat hiermee de postoperatieve pijn het best kan worden bestreden5. Ook maakt het een vroege mobilisatie mogelijk, waardoor de kans op postoperatieve pulmonale complicaties kleiner wordt6. Het monitoren van de neuromusculaire blokkade tijdens de operatie is belangrijk om restverslapping op het einde van de OK uit te sluiten. restverslapping wil je zeker bij de pulmonaal belaste patiënt voorkomen. als er maar enigszins restverslapping aanwezig is, antagoneer ik, na gebruik van esmeron® (rocuronium), standaard met Bridion. Juist in deze patiëntengroep wil je bijwerkingen zoals bronchospasme en slijmvorming (naast de brady/tachycardie) van de neostigmine/ atropine combinatie voorkomen7. Daarnaast heb je de zekerheid dat door het werkingsmechanisme van Bridion, (alle nog aanwezige spierrelaxans zal worden geïnactiveerd) de patiënt weer over zijn/haar volledige spierkracht kan beschikken, zodat de patiënt direct postoperatief goed kan ophoesten en doorademen8. In het afgelopen jaar hebben we veel ervaring opgedaan met het gebruik van Bridion, we zijn zeer enthousiast. Bridion heeft in onze praktijkvoering een vaste en niet meer weg te denken plaats gekregen.

Referenties: 1.

Murphy et al; MInerVa aneSteSIOl 2006;72:97-109

5.

Ballantyne et al; anesth analg 1998;86:598-612)

2.

Murphy et al; anesth analg 2010;111:120–8

6.

rodgers et al; BMJ 2000; 321: 1-12

3.

Stuurgroep Zichtbare Zorg voor de pulmonaal belaste patiënt

7.

Smpc tekst neostigmine en atropine

4.

lawrence et al ann Intern Med 2006; 144: 596-608

8.

Smpc tekst Bridion

2010-nl-539

Restverslapping is een bekend verschijnsel bij het gebruik van spierverslappers. Restverslapping wordt door een gebrek aan objectieve monitoring, echter vaak nog niet goed (h)erkend. Om restverslapping uit te sluiten is het daarom belangrijk te zorgen voor een objectieve monitoring. De gouden standaard voor een veilige extubatie is een TOF ratio waarde van 90%1. Een restverslapping (TOF ratio < 90%) kan leiden tot pulmonale complicaties postoperatief2.

Dit interview is mogelijk gemaakt door MSD nederland

2010 NL 539 Bridion advertorial 6.indd 1 2010 Eldering_NTvA 04 v3.indd 29

01-09-10 10:58 10-09-10 12:03

Advertentie

Referenties: 1. SmPC Instanyl® 50, 100, 200 µg/dosis, juli 2009 2. Christrup LL et al. Pharmacokinetics, efficacy, and tolerability of fentanyl following intranasal versus intravenous administration in adults undergoing third-molar extraction: a randomized, double-blind, double-dummy, two-way, crossover study. Clin Ther 2008;30:469-481 3. Kress HG et al. Efficacy and tolerability of intranasal fentanyl spray 50 to 200 mg for breakthrough pain in patients with cancer: a phase III, multinational, randomized, double blind, placebo-controlled, crossover trial with a 10-month, open-label extension treatment period. Clin Ther 2009;31 4. Mercadante S et al. A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain – an open-label, randomised, crossover trial. Curr Med Res Opin 2009;25(11):2805-2815

Nieuw verschenen bij De Tijdstroom

Instanyl 50 microgram/dosis neusspray, oplossing. Instanyl 100 microgram/dosis neusspray, oplossing. Instanyl 200 microgram/dosis neusspray, oplossing. Kwalitatieve en kwantitatieve samenstelling: 1 ml oplossing bevat fentanylcitraat equivalent aan respectievelijk 500, 1000 en 2000 microgram fentanyl. 1 dosis (100 microliter) bevat respectievelijk 50, 100 en 200 microgram fentanyl. Farmaceutische vorm: Neusspray, oplossing. Heldere, kleurloze oplossing. Therapeutische indicaties: Instanyl is geïndiceerd voor de behandeling van doorbraakpijn bij volwassenen die al een onderhoudsbehandeling met opioïden ontvangen tegen chronische kankerpijn. Doorbraakpijn is een tijdelijke exacerbatie van pijn die optreedt bovenop een bestaande, aanhoudende pijn die reeds onder controle is. Patiënten die een onderhoudsbehandeling met opioïden ontvangen, gebruiken minstens 60 mg orale morfine per dag, minstens 25 microgram transdermale fentanyl per uur, minstens 30 mg oxycodon per dag, minstens 8 mg orale hydromorfon per dag of een equianalgetische dosis van een ander opioïd gedurende één week of langer. Dosering en wijze van toediening: De behandeling dient te worden ingesteld door en onder toezicht te blijven van een arts met ervaring in de behandeling van kankerpatiënten met opioïden. Voor verdere informatie, zie de volledige IB-tekst. Contra-indicaties: Overgevoeligheid voor het werkzame bestanddeel of voor één van de hulpstoffen. Gebruik bij opioïd-naïeve patiënten. Ernstige respiratoire depressie of ernstige obstructieve longaandoeningen. Eerdere faciale radiotherapie. Terugkerende epistaxisaanvallen. Bijzondere waarschuwingen en voorzorgen bij gebruik: Zoals bij alle krachtige opioïden kan er klinisch significante respiratoire depressie optreden bij gebruik van fentanyl en moeten patiënten geobserveerd worden op deze effecten. Patiënten met pijn die een chronische opioïdbehandeling ontvangen, ontwikkelen een tolerantie voor respiratoire depressie en dus is het risico op respiratoire depressie bij deze patiënten lager. Gelijktijdig gebruik van geneesmiddelen die het centrale zenuwstelsel onderdrukken kan het risico op respiratoire depressie verhogen. Bij patiënten met chronische obstructieve longaandoeningen kan fentanyl ernstigere bijwerkingen hebben. Bij deze patiënten kunnen opioïden de ademhalingsprikkel onderdrukken en de weerstand van de luchtwegen verhogen. Fentanyl dient met zorg te worden toegediend aan patiënten met matige tot ernstige lever- of nierfunctiestoornissen. De invloed van leveren nierfunctiestoornissen op de farmacokinetiek van Instanyl is niet geëvalueerd; wanneer fentanyl echter intraveneus wordt toegediend, is de klaring gewijzigd als gevolg van leveren nierfunctiestoornissen, veroorzaakt door veranderingen in metabole klaring en plasma-eiwitten. Fentanyl dient met zorg te worden gebruikt bij patiënten met tekenen van een verhoogde intracraniale druk, een verminderd bewustzijn of coma. Instanyl dient met zorg te worden gebruikt bij patiënten met een hersentumor of hoofdletsel. Fentanyl kan bradycardie veroorzaken. Fentanyl dient daarom met zorg te worden toegediend aan patiënten met bradyaritmie. Opioïden kunnen hypotonie veroorzaken, vooral bij patiënten met hypovolemie. Instanyl dient daarom met zorg te worden gebruikt bij patiënten met hypotonie en/of hypovolemie. Als de patiënt herhaalde episodes van epistaxis of nasaal ongemak ervaart bij het gebruik van Instanyl, dient een andere toedieningsvorm voor de behandeling van doorbraakpijn overwogen te worden. De totale blootstelling aan fentanyl bij personen met een verkoudheid, zonder eerdere behandeling met een nasale vasoconstrictor, is vergelijkbaar met die bij gezonde personen. Tolerantie en lichamelijke en/ of psychische fhankelijkheid kan optreden na herhaald gebruik van opioïden zoals fentanyl. Iatrogene verslaving na therapeutisch gebruik van opioïden komt echter zelden voor bij de behandeling van kankergerelateerde pijn. Ontwenningsverschijnselen kunnen optreden door de toediening van stoffen met opioïd-antagonistische activiteit, bijv. naloxon, of door analgetica met een gecombineerde agonistische en antagonistische werking (bijv. pentazocine, butorfanol, buprenorfine, nalbufine). Wanneer de behandeling met Instanyl wordt gestart, dienen andere toedieningsvormen overwogen te worden voor gelijktijdige behandeling van samenlopende ziektes die via de neus kunnen worden behandeld. Bijwerkingen: Met het gebruik van Instanyl kunnen typische opioïd-gerelateerde bijwerkingen worden verwacht. Vaak zullen na voortgezet gebruik van het geneesmiddel de meeste van deze bijwerkingen verdwijnen of in intensiteit afnemen. De meest ernstige bijwerkingen zijn respiratoire depressie (mogelijk leidend tot apneu of ademstilstand), circulatoire depressie, hypotensie en shock. Alle patiënten dienen nauwlettend te worden geobserveerd op deze bijwerkingen. De volgende categorieën worden gebruikt om de bijwerkingen volgens frequentie van voorkomen te rangschikken: zeer vaak (≥1/10); vaak (>1/100 en <1/10); soms (>1/1.000 en <1/100); zelden (>1/10.000 en <1/1.000); en zeer zelden (<1/10.000), niet bekend (kan met de beschikbare gegevens niet worden bepaald). Binnen elke frequentiegroep worden bijwerkingen gerangschikt naar afnemende ernst. Psychische stoornissen: Soms: afhankelijkheid, insomnia. Zenuwstelselaandoeningen: Vaak: somnolentie, duizeligheid, hoofdpijn. Soms: sedatie, myoclonus, paresthesie, dysesthesie, dysgeusie. Evenwichtsorgaan- en ooraandoeningen: Vaak: vertigo. Soms: kinetosis. Hartaandoeningen: Soms: hypotensie. Bloedvataandoeningen: Vaak: blozen, opvliegers. Ademhalingsstelsel-, borstkast- en mediastinumaandoeningen: Vaak: keelirritatie. Soms: respiratoire depressie, epistaxis, neuszweer, rhinorrhea. Maagdarmstelselaandoeningen: Vaak: misselijkheid, braken. Soms: constipatie, stomatitis, droge mond. Huid- en onderhuidaandoeningen: Vaak: hyperhidrose. Soms: pijnlijke huid, pruritus. Algemene aandoeningen en toedieningsplaatsstoornissen: Soms: pyrexie. Overige informatie: Farmacotherapeutische groep: fenylpiperidinederivaten. ATC-code: N02AB03. Kanalisatie: UR. Registratiehouder: Nycomed Danmark ApS, Langebjerg 1, DK-4000 Roskilde, Denemarken. Volledige informatie is verkrijgbaar via de lokale vertegenwoordiger in Nederland: Nycomed bv, Hoofddorp. In het Register ingeschreven onder EU/1/09/531/001-009.

Klinische anesthesiologie dr. P.G. Noordzij dr. M. Klimek A.J. Stamer [redactie]

Ook beschikbaar: Klinische anesthesiologie

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Medicatie

Redactie: dr. P.G. Noordzij dr. M. Klimek A.J. Stamer ISBN 9789058981608 195 x 270 mm. 574 blz. Gebonden E 65,00

De Tijdstroom Uitgeverij BV Postbus 775 3500 AT Utrecht 030 2364450 [email protected] Voor meer informatie: www.klinische-anesthesiologie.nl www.tijdstroom.nl

Ts Adv. Klinische anesthesiologie.indd 1

Zeker Zaldiar

Voor ondersteunend educatief materiaal, zie www.instanyl.nl (augustus 2009)

Launch bijsluiter 09-09-10 11:26

90x120mm.indd 1

Verkorte productinformatie Bridion 100 mg/ml oplossing voor injectie

Referenties: 1. Registratietekst Zaldiar. 2. Rosenthal et al. J Am Geriatr Soc. 2004 Mar;52(3):374-380. 3. Silverfield et al. Clin Ther. 2002 Feb;24(2):282-297. 4. Emkey et al. J Rheumatol. 2004 Jan;31(1):150-6.

ZAL-ADV-20100426-16

Verkorte Productinformatie Zaldiar® / Zaldiar® Bruis 37,5 mg/325 mg Samenstelling: ZALDIAR filmomhulde tabletten en ZALDIAR BRUIS bruistabletten bevatten 37,5 mg tramadol en 325 mg paracetamol. Indicaties: ZALDIAR en ZALDIAR BRUIS zijn bestemd voor de symptomatische behandeling van matige tot ernstige pijn. Dosering: Het wordt aanbevolen de behandeling te starten met twee (bruis)tabletten, maximale dosering per dag is acht (bruis)tabletten (overeenkomend met 300 mg tramadol en 2600 mg paracetamol). ZALDIAR en ZALDIAR BRUIS worden niet aanbevolen bij kinderen jonger dan 12 jaar. Contra-indicaties: Overgevoeligheid voor tramadol, paracetamol of voor één van de hulpstoffen. Acute intoxicatie met alcohol, hypnotica, centraal werkende analgetica, opioïden of psychotrope middelen. Gebruik van MAO-remmers, ernstige leverfunctiestoornissen, epilepsie die niet voldoende onder controle is door middel van behandeling. Speciale waarschuwingen: ZALDIAR en ZALDIAR BRUIS worden niet aanbevolen bij patiënten met ernstige nierinsufficiëntie (creatinineklaring < 10 ml/min) of bij ernstige ademhalingsinsufficiënte. Niet gelijktijdig gebruiken met andere paracetamol of tramadol bevattende geneesmiddelen zonder een arts te raadplegen. Epilepsiepatiënten die met behandeling onder controle zijn of patiënten die ontvankelijk zijn voor aanvallen, mogen alleen met ZALDIAR of ZALDIAR BRUIS worden behandeld als dat absoluut noodzakelijk is. Gelijktijdig gebruik van opioïd-agonisten-antagonisten (nalbufine, buprenorfine, pentazocine) wordt niet aangeraden. ZALDIAR en ZALDIAR BRUIS moeten met voorzichtigheid worden gebruikt bij opioïd-afhankelijke patiënten of bij patiënten met een craniaal trauma, met een aanleg voor convulsieve aandoeningen, galwegaandoeningen, in een toestand van shock, in een toestand van veranderd bewustzijn van onbekende oorzaak, met problemen van het ademhalingscentrum of de ademhalingsfunctie, of met een verhoogde intracraniale druk. Interacties: MAO-remmers, alcohol, carbamazepine en andere enzyminductoren, opioïd-agonisten-antagonisten, SSRI’s, triptanen, andere opioïdderivaten, benzodiazepinen, barbituraten, anxiolytica, hypnotica, sedatieve antidepressiva, sedatieve antihistaminica, neuroleptica, centraal werkende antihypertensieve middelen, thalidomide, baclofen, warfarines, andere geneesmiddelen waarvan bekend is dat ze CYP3A4 remmen, bupropion. Meest voorkomende bijwerkingen: misselijkheid, duizeligheid en slaperigheid, hoofdpijn, beven, verwardheid, stemmingswisselingen, slaapstoornissen, braken, constipatie, droge mond, diarree, abdominale pijn, dyspepsie, flatulentie, zweten, pruritus. Houdbaarheid: ZALDIAR 3 jaar / ZALDIAR BRUIS 2 jaar. Verpakking en prijs: ZALDIAR 30 of 60 tabletten per verpakking / ZALDIAR BRUIS 30 tabletten per verpakking. Prijs: zie Z-Index taxe. Registratienummer: ZALDIAR RVG 28113 / ZALDIAR BRUIS RVG 101592. Afleverstatus: UR. Vergoeding: volledig vergoed. Datering IB tekst: ZALDIAR April 2008 en ZALDIAR BRUIS Maart 2010. Volledige productinformatie is op aanvraag verkrijgbaar: Grünenthal B.V., Kosterijland 70-78, 3981 AJ Bunnik. Tel: 030 – 60 463 70. E-mail: [email protected]

Samenstelling: 1 ml Bridion 100mg/ml, oplossing voor injectie, bevat sugammadex als natriumzout equivalent aan 100 mg sugammadex. Elke ml bevat 9,7 mg natrium. Indicatie: Opheffing van de door rocuronium of vecuronium geïnduceerde neuromusculaire blokkade. Bij kinderen en adolescenten wordt het gebruik van sugammadex alleen aanbevolen bij standaardopheffing van een door rocuronium geïnduceerde neuromusculaire blokkade. Dosering: Sugammadex dient intraveneus te worden toegediend als eenmalige bolusinjectie. Sugammadex mag alleen worden toegediend door of onder supervisie van een anesthesist. Het gebruik van een geschikte neuromusculaire monitortechniek wordt aanbevolen om het herstel van de neuromusculaire blokkade te bewaken. De aanbevolen dosis sugammadex is afhankelijk van het niveau van de neuromusculaire blokkade. De aanbevolen dosis is niet afhankelijk van de toegediende anesthesie. Bridion kan worden verdund tot 10 mg/ml ten behoeve van een betere nauwkeurigheid van de dosering bij kinderen (zie rubriek 6.6*). Standaardopheffing: Er wordt een dosis van 4 mg/kg sugammadex aanbevolen indien het herstel ten minste 1-2 posttetanische tellingen (PTC) heeft bereikt na een door rocuronium of vecuronium geïnduceerde blokkade. Een dosis van 2 mg/kg sugammadex wordt aanbevolen als spontaan herstel is opgetreden tot minimaal het terugkeren van T2 na een door rocuronium of vecuronium geïnduceerde blokkade. Bij kinderen en adolescenten (2 17 jaar) wordt voor standaardopheffing bij terugkeer van T2 na een door rocuronium geïnduceerde blokkade 2 mg/ kg sugammadex aanbevolen. Andere situaties van standaardopheffing bij kinderen en adolescenten zijn niet onderzocht en worden daarom niet aanbevolen. Het gebruik van sugammadex bij voldragen pasgeborenen en zuigelingen wordt niet aanbevolen. Onmiddellijke opheffing: Als er klinische noodzaak bestaat van onmiddellijke opheffing na toediening van rocuronium, wordt een dosis van 16 mg/kg sugammadex aanbevolen. Onmiddellijke opheffing is bij kinderen en adolescenten niet onderzocht en wordt daarom niet aanbevolen. Hernieuwde toediening sugammadex: In de uitzonderlijke situatie dat zich postoperatief, na een initiële dosis van 2 mg/ kg of 4 mg/kg, opnieuw een blokkade voordoet (zie rubriek 4.4*), wordt een herhalingsdosis van 4 mg/kg sugammadex aanbevolen. Contra-indicaties: Overgevoeligheid voor het werkzame bestanddeel of voor één van de hulpstoffen. Waarschuwingen: Patiënten moeten kunstmatig worden beademd totdat de spontane ademhaling voldoende is hersteld. Andere geneesmiddelen, die tijdens en na de operatie zijn gebruikt, kunnen de ademhalingsfunctie onderdrukken. In geval dat hernieuwd optreden van een neuromusculaire blokkade wordt waargenomen, kunnen kunstmatige beademing en hernieuwde toediening van sugammadex noodzakelijk zijn (zie rubriek 4.2*). Om hernieuwd optreden van neuromusculaire blokkade te voorkomen, dienen de aanbevolen doses van sugammadex te worden gebruikt. Een verhoogd risico op bloedingen kan niet worden uitgesloten bij patiënten: met erfelijke vitamine K afhankelijke stollingsfactorgerelateerde deficiënties; met reeds bestaande coagulopathiën; die coumarinederivaten gebruiken en met een INR boven 3,5; die antistollingsmiddelen gebruiken en een dosis van 16 mg/kg sugammadex ontvangen. Sugammadex mag niet worden gebruikt voor opheffing van blokkades geïnduceerd door niet steroïde neuromusculair blokkerende stoffen en door steroïde neuromusculair blokkerende stoffen, anders dan rocuronium of vecuronium. Indien de neuromusculaire blokkade wordt opgeheven onder voortzetting van de anesthesie, dienen aanvullende doses van het anestheticum en/of opioïd te worden gegeven op geleide van de klinische indicatie. Indien hernieuwde neuromusculaire blokkade is vereist vóór het verstrijken van de aanbevolen wachttijd van 24 uur, dient een niet-steroïde neuromusculair blokkerende stof te worden gebruikt. Sugammadex is niet onderzocht bij patiënten, die rocuronium of vecuronium krijgen op de Intensive Care. Mogelijke interacties: In situaties waar mogelijke verdringingsinteracties verwacht kunnen worden, dienen patiënten (na parenterale toediening van een ander geneesmiddel binnen 6 uur na toediening van sugammadex) zorgvuldig gecontroleerd te worden op tekenen van hernieuwd optreden van een blokkade (voor maximaal ongeveer 15 minuten). In situaties waar mogelijke bindingsinteracties kunnen optreden wordt de arts geadviseerd om het geneesmiddel opnieuw toe te dienen of de toediening van een therapeutisch gelijkwaardig geneesmiddel en/of niet farmacologische interventies te overwegen (zie rubriek 4.5*). Nierfunctiestoornis: Het gebruik van sugammadex bij patiënten met een ernstige nierfunctiestoornis wordt niet aanbevolen. Leverfunctiestoornis: Patiënten met een ernstige leverfunctiestoornis moeten met grote voorzichtigheid worden behandeld. Vertraagd herstel: Aandoeningen waarbij sprake is van een verlengde circulatietijd, zoals cardiovasculaire aandoeningen, gevorderde leeftijd of oedeemvorming kunnen gepaard gaan met langere hersteltijden. Allergische reacties: Artsen moeten voorbereid zijn op de mogelijkheid van allergische reacties en de nodige voorzorgsmaatregelen treffen. Natriumbeperkt dieet: Indien er meer dan 2,4 ml oplossing moet worden toegediend, dient hier rekening mee te worden gehouden bij patiënten met een natriumbeperkt dieet. Verlenging van het QTc-interval: De routinematige voorzorgsmaatregelen voor de behandeling van aritmie moeten in overweging worden genomen. Pediatrische populatie: De interacties en waarschuwingen voor volwassenen gelden ook voor kinderen. Interacties: Voor toremifeen kunnen verdringingsinteracties niet worden uitgesloten. Het gebruik van fusidinezuur in de preoperatieve fase kan het herstel van de T4/T1 ratio tot 0,9 enigszins vertragen. Voor hormonale anticonceptiva kon een klinisch relevante bindingsinteractie niet worden uitgesloten. In het algemeen interfereert sugammadex niet met laboratoriumtests, met als mogelijke uitzondering de progesteronbepaling in serum. Doseringen van 4 mg/kg en 16 mg/kg sugammadex kunnen de geactiveerde partiële tromboplastinetijd (aPTT) en protrombinetijd (PT) voor korte duur (< 30 minuten) licht verlengen. Bijwerkingen: De veiligheid van sugammadex is beoordeeld op basis van een geïntegreerde veiligheidsdatabase van ongeveer 1700 patiënten en 120 vrijwilligers. Zeer vaak: Dysgeusie (metalen of bittere smaak), werd vooral waargenomen na doses van 32 mg/kg sugammadex of hoger. Vaak: Complicaties bij anesthesie, indicatief voor herstel van neuromusculaire functie. Soms: In een paar gevallen zijn allergieachtige reacties (bijv. bloedstuwing, erythemateuze huiduitslag) gerapporteerd na gebruik van sugammadex waarvan er een als milde allergische reactie is bevestigd. Na behandeling met sugammadex zijn enkele gevallen van awareness gerapporteerd. Hernieuwd optreden van een blokkade: De incidentie van het hernieuwd optreden van een blokkade was 2% na gebruik van sugammadex en 0% in de placebogroep. Vrijwel al deze gevallen kwamen voor in dose finding onderzoeken met suboptimale doses (minder dan 2 mg/kg) (zie rubriek 4.4*). Longpatiënten: Net als bij alle patiënten met een voorgeschiedenis van longcomplicaties, dient de arts zich bewust te zijn van het mogelijke optreden van bronchospasmen. Houder van de vergunning voor het in de handel brengen: N.V. Organon, Kloosterstraat 6, 5349 AB Oss, Nederland. Nummers van de vergunning voor het in de handel brengen: EU/1/08/466/001-2 Afleverstatus: U.R. Datum van eerste verlening van de vergunning: 25 juli 2008. Datum van wijziging van de (verkorte) productinformatie: 2 juni 2010 * Voor de volledige productinformatie verwijzen wij naar de huidig goedgekeurde SPC.

Nu ook als bruis beschikbaar

100727 Bridion bijsluiter zww1.indd 1


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groep 4: divers

In vitro testing of a computer-driven model for Sevoflurane infusion through AnaConDa® C.R.M. Barends1, J.K. Oosterhuis1, Ir. T. De Smet2, M. Enlund3, M.M.R.F Struys1

1

Universitair Medisch Centrum Groningen, GRONINGEN, the Netherlands 2 Demed, TEMSE, Belgium 3 Department of Anesthesia & Intensive Care, Central Hospital, VÄSTERAS, Sweden

Introduction AnaConDa® (Sedana Medical AB) is a disposable device for Sevoflurane delivery using high-flow semi-open systems. The dosing nomogram requires manual setting of the syringepump to control end-tidal concentrations. Enlund et al. proposed a 2-compartment model of the pharmacokinetics for Sevoflurane for AnaConda® . We tested proof of concept and safety combining this model as a computer-driven delivery-paradigm with AnaConDa.

Methods AnaConDa® was used with a syringepump (Alaris Asena® TIVA Mk II), Dräger Primus ventilator and Dräger LungensimulatorLS800. Sevoflurane infusion rates where regulated using RuGLoopII programmed with Enlunds model. 200ml/min was sampled from the gasmixture and CO2 added, maintaining etCO2 at 28-35 mmHg and FiO2 at 38-40%, emulating patient ventilation. 3,5 and 7 liters Minute Volumes (MV) were tested. 10 testruns (5 for both 3,5 and 7,0ltr MV) consisted of 4 consecutive 45 minute periods. Central compartmental concentrations during these periods were targeted at 0,5%, 0,75%, 1,0%. and 0% respectively. Observed versus predicted end-tidal concentrations were compared using prediction error calculations.

Results At 3,5ltr MV mean (±SD) median prediction error (MDPE) was 233,77% (±16,66),

Caption 1. Measured etSevo% at 3,5ltr MV

mean (±SD) median absolute prediction error (MDAPE) was 233,77% (±16,66), mean (±SD) wobble was 28,29% (±6,18). At 7,0ltr MV mean MDPE was 182,98% (±10,97), mean MDAPE 182,98% (±10,97), mean wobble 29,66% (±5,16). Overshoot was apparent throughout all runs. During testing, we revealed additionally that temperature and angulation had to be kept constant within minute margins. Angulation of AnaConDa® from the horizontal plane quickly and consistently lead to liquid Sevoflurane collecting in AnaConDa® and the endotracheal tube, as was the case with temperature drops of more than 1°C.

Conclusion Combining AnaConDa® and the proposed computer-driven model does not seem to be accurate. Observed end-tidal concentrations were much higher than predicted.

Caption 2. Measured etSevo% at 7,0ltr MV

groep 4: divers

The effects of epidural analgesia on delivery in a dutch teaching hospital: does the rate of caesarean section or instrumental delivery increase? P. Bruins1, A.C. Werger, L.S.M. Ribbert2, M.E. Kars1, H.P.A van Dongen1

1

Department of Anesthesiology, Intensive Care and pain Medicine, St Antonius Ziekenhuis Nieuwegein, NIEUWEGEIN, the Netherlands 2 Department of Obstetrics and Gynecology, St Antonius Ziekenhuis Nieuwegein, NIEUWEGEIN, the Netherlands


Introduction

Methods

There is consensus that epidural analgesia does not increase the risk of caesarean section, however controversy remains whether it increases the risk of instrumental vaginal delivery. We conducted a retrospective review of patients admitted for vaginal delivery to evaluate the effect of epidural analgesia on caesarean section and instrumental delivery rates.

Between January 1st and September 30th 2009, 1.364 women with singleton pregnancies, started labor at a gestational age ≥ 36 weeks. This population was divided in an epidural and a non-epidural group, and subdivided in a nulliparous and a multiparous group.

Results Of the 1.364 parturients (736 nullipara (54%)

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abstracts 2010 and 628 multipara (46%)), 504 requested epidural analgesia (37%). Of these, 358 were nulliparous (71%) and 146 multiparous (29%). More instrumental deliveries were seen in the nulliparous non-epidural group compared to the nulliparous epidural group (32.5% vs. 25.4 %, p< 0.033), the multiparous population showed no difference (7.5 % vs. 4.8%). However, the caesarean

section rate showed an increase in both parity groups with epidural analgesia (nulliparous 22.1% vs. 12.7 %, p<0.001 and multiparous 16.4 vs 6.8%, p<0.001). When corrected for birth weight, maternal age, early initiation of epidural (< 4 cm cervix dilatation) and for previous caesarean section (multiparous group only), the increase was still significant.

Conclusion In our hospital epidural analgesia did not increase the risk for instrumental delivery. However, the risk of a caesarean section increased in both nulliparous and multiparous parturients.

groep 4: divers

Can sugammadex save a patient in a simulated ‘cannot intubate cannot ventilate’ situation at a large teaching hospital? M.M.A. Bisschops, C Holleman, J.M. Huitink VU medisch centrum, Amsterdam, the Netherlands

Introduction The main advantage of succinylcholine over rocuronium is a fast spontaneous recouvery of the neuromuscular blockade. Recent studies have shown that administration of sugammadex after a high dose rocuronium provides a faster time to recouvery. The intubation conditions are comparable when rocuronium is compared to succinylcholine and rocuronium will provide a blockade faster. In our study we wanted to measure the time it takes from the decision to reverse the effect of a rocuronium until the actual intravenous administration of sugammadex.


Methods In a room in our operation complex we simulated a normal operating theatre. We asked 18 teams of either anaesthetists and nurse (A-team) either anaesthetists-trainee and nurse (AT-team) to prepare and administer sugammadex to a patient who had just been given a high dose rocuronium. We made sure all materials involved could be found at the normal place.

Results Our patient should have received 113 (kg) x 16 (mg) = 1808mg sugammadex. Only 4 teams gave a correct dose. The mean total time until administration of sugammadex was 402 ± 90 seconds. None of the A-teams gave the correct dose versus 4 out of 11 of the AT-teams. The teams that overdosed gave 2000 mg

sugammadex. The teams that gave too less administered 1600 mg and one AT-team team gave 1400 mg sugammadex.

Conclusions During a simulated case of cannot intubate cannot ventilate, our anesthesia teams had difficulty with the timely administration of the correct dose of sugammadex shortly after the introduction for clinical use. The fastest time to administer sugammadex in our study was 130 seconds (investigators) after which it will take 130 seconds for the TOF ratio to recouver to 0.9. The mean time was until administration was 402 seconds after which critical desaturation will most likely occur.

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Changing tomorrow

Innovatie in pijn management Onder het motto ‘Changing tomorrow’ zet Astellas zich in om een aantal uitdagende medische aandoeningen op een fundamenteel andere, innovatieve wijze aan te pakken. Pijnbehandeling is één van deze speerpunten. De fysieke en emotionele uitdagingen die patiënten met pijn ervaren staan hierbij centraal. Astellas werkt vanuit die optiek in haar R&D programma aan alternatieve oplossingen om de pijn te bestrijden. Momenteel werkt Astellas aan nieuwe, eﬀectieve behandelingen om het lichamelijk en geestelijk lijden van patiënten met pijn zo goed mogelijk te verlichten. Met een zo minimaal mogelijke belasting voor de patiënt. In de hoop en overtuiging de dag van morgen voor pijnpatiënten structureel te veranderen. www.astellas.nl 2010 Eldering_NTvA 04 v3.indd 3

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Nu kunt u snel en veilig antagoneren onafhankelijk van diepte

BRIDION® heft snel en veilig het neuromusculaire blok op, onafhankelijk van de diepte:

bridion_adv_NtvA.indd 1 2010 Eldering_NTvA 04 v3.indd 4

Nu ook snelle opheffing van een diep blok – 2,7 minuten bij een rocuronium blok* – 3,3 minuten bij een vecuronium blok* Weinig kans op bijwerkingen Geen anticholinergica nodig

NIEUW 2008-NL-467

* Mediane waarde Verkorte productinformatie zie elders in dit blad

Uniek werkingsmechanisme: BRIDION inactiveert rocuronium en vecuronium door inkapseling.

Grip op spierverslapping 23-02-2009 12:17:03 10-09-10 12:07

anesthesiologie Nederlands tijdschrift voor Wetenschap special volume 22, september Selectie van abstracts C. Boer Abstracts Wetenschapsdag 2010

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