Netherlands Journal. I.A. Meynaar, P.L. Tangkau, B.C. Verdouw, M. Wagemans, L. Dawson, E.F.Salm, F. Borst

Netherlands NetherlandsJournal Journal o o ff cCrr ii ttiiccaall Ccaarree

b i - m o n t h ly o f f i c i a l j o u r n a l

o f t h e d u t c h s o c i e t y o f i n t e n s i v e care (nvic)

Volume 10, No. 4 August 2006

In this issue

c a s e r e p o rt

Local toxicity of potassium chloride

479

B.L. Hübner c a s e r e p o rt

A case of mannitol-induced hyponatraemia, renal failure and respiratory insufficiency

480

I.A. Meynaar, P.L. Tangkau, B.C. Verdouw, M. Wagemans, L. Dawson, E.F.Salm, F. Borst review

Subarachnoid haemorrhage: a disorder requiring multidisciplinary intensive care

482

C. Hoedemaekers, J. De Vries, T. van der Vliet, F.E. De Leeuw, P.E. Vos, J.H. van der Hoeven review

Electrical impedance tomography

487

I. Frerichs, J. Scholz, N. Weiler review

What are the consequences of peepi during spontaneous and controlled ventilation in patients with chronic obstructive lung disease

494

L M. Dijkema, J.E. Tulleken, J.J.M Ligtenberg, J.H.J Meertens, J.S.W Lind, J.G. Zijlstra review

Critical Care and Emergency Research in the European Union under the European Clinical Trials Directive 2001/20/EC: Recommendations of the ‘VISEAR’ working group

498

E.J.O. Kompanje original

Dexamethasone in paediatric cardiac surgery; implications using two surrogate markers

502

I. Malagon, W. Onkenhout, J.G. Bovill, M.G. Hazekamp NVICatern

Nederlandse Vereniging

voor

Intensive Care (NVIC)

V NJCC_04 omslag 01.indd 2

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16-08-2006 13:58:58

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TOTAL PERFORMANCE SPEED STRENGTH ENDURANCE 06.tyg.6.8 Productinformatie zie elders in dit blad.

is all about:

Voor productinformatie zie elders in dit blad

NJCC_04 omslag 01.indd 3

16-08-2006 13:58:59

n eth e rlan ds jou rnal of critical care

Colophon Executive editorial board AB Johan Groeneveld, Editor in Chief Arthur RH van Zanten, Managing Editor Kees H Polderman, Internet Editor Peter HJ van der Voort, Correspondence Editor

ournal Netherlands J of critical care Vol. 10, No. 4, August 2006

Publisher Netherlands Journal of Critical Care issn: 1569-3511 nvic Stationsweg 73C 6711 PL Ede (Gld) Telephone: +31-318-69 33 37 Fax: +31-318-69 33 38 KvK Utrecht V30149527 Production

Information for authors

475

Case reports Local toxicity of potassium chloride B.L. Hübner

479

• A case of mannitol-induced hyponatraemia, renal failure and

480

Reviews Subarachnoid haemorrhage: a disorder requiring multidisciplinary intensive care C. Hoedemaekers, J. De Vries, T. van der Vliet, F.E. De Leeuw, P.E. Vos, J.H. van der Hoeven

•

482

• Electrical impedance tomography I. Frerichs, J. Scholz, N. Weiler • What are the consequences of peepi during spontaneous and controlled

487

•

Interactie, Ede Design v i l l a y, The Hague Layout Unit-1, The Hague Printing Perfect DM Groep, Rotterdam Advertising-exploitation/ Business contacts Eldering Studio BV Thomas Eldering Communication and media-specialists Zijlweg 12 2051 BA Overveen Telephone: +31-23-52 59 332 Fax: +31-23-52 53 265 E-mail: [email protected] Internet address Dutch IC society: www.nvic.nl Bankaccount ABN AMRO Ede 52.45.61.893 IBAN

NL 55ABNA0524561893

BIC

ABNANL 2 A

NVIC membership and subscriptions

respiratory insufficiency I.A. Meynaar, P.L. Tangkau, B.C. Verdouw, M. Wagemans, L. Dawson, E.F.Salm, F. Borst

ventilation in patients with chronic obstructive lung disease L M. Dijkema, J.E. Tulleken, J.J.M Ligtenberg, J.H.J Meertens, J.S.W Lind, J.G. Zijlstra

• Critical Care and Emergency Research in the European Union

494

498

under the European Clinical Trials Directive 2001/20/EC: Recommendations of the ‘VISEAR’ working group E.J.O. Kompanje

Original Dexamethasone in paediatric cardiac surgery; implications using two surrogate markers I. Malagon, W. Onkenhout, J.G. Bovill, M.G. Hazekamp

•

502

One year NVIC-membership costs € 165 (for registered intensivist) or € 110(otherwise). These costs include a subscrition for the Neth J Crit Care. Separate issues are available for € 27,50 excluding 6% VAT. Prices subject to change without notice. Further information can be obtained by telephone at +31-318-69 33 37 or by fax at +31-318-69 33 38 Copyright © 2006 nvic All information contained in this issue is the property of the NVIC. Reproduction in any kind is prohibited without prior written permission by the NVIC.

NVICatern

• Commissies en Afgevaardigden • Verenigingsnieuws • Agenda • Inschrijvingsformulier

n eth j crit care • volume 10 • no 4 • august 2006

NJCC_04 binnenwerk 01.indd 473

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(advertenties)

Scheper Ziekenhuis Emmen Het Scheper Ziekenhuis Emmen beschikt over een goed geoutilleerde Intensive Care (8 beademingsbedden) in combinatie met een Medium care (6 bedden). De intensivisten zijn hoofdbehandelaar op de IC. De afgelopen jaren heeft de Intensive Care van het Scheper Ziekenhuis een behoorlijke groei doorgemaakt, zowel in het aantal behandeldagen als in inhoudelijke ontwikkelingen. Zo is het afgelopen jaar een Patiënt Data Management Systeem ingevoerd. Het Scheper Ziekenhuis heeft besloten de IC door te ontwikkelen tot een Level 2 Intensive Care. Het ziekenhuis is momenteel bezig met het opzetten van een regionale samenwerkingsstructuur met andere omliggende ziekenhuizen. Om te kunnen voldoen aan de vraag uit het eigen verzorgingsgebied en de regio, is het ziekenhuis voornemens de IC-capaciteit in de aankomende jaren uit te breiden naar 12 IC beademingsbedden en 8 Medium Care bedden. Gezien de groei van de werkzaamheden op de Intensive Care is het ziekenhuis voornemens een nieuwe Maatschap Intensive Care op te richten.

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3 Intensivisten

Acquisitie n.a.v. deze advertentie wordt beslist niet op prijs gesteld.

Uw profiel U bent een (binnenkort) geregistreerd intensivist, beschikt over goede contactuele eigenschappen en werkt graag in multidisciplinair teamverband aan de zorg van de Intensive- en Medium Care patiënten. U bent gedreven en heeft visie op het verder innoveren van de Intensive Care geneeskunde samen met de collega’s in het regionale samenwerkingverband met de omliggende ziekenhuizen. Deeltijd werken is bespreekbaar. Procedure Nadere informatie over de functie kan worden verkregen bij de heer P.N.Th.M. Windt, voorzitter Raad van Bestuur, (0591) 69 18 00, bij de heer W. van der Hoek, internist-intensivist, (0591) 69 13 60 en Dr. L.S. Hofstra, internist-intensivist, (0591) 69 13 86.

De Zorggroep Suydevelt bundelt de krachten van een aantal zorginstellingen in de regio Zuidoost Drenthe, met als belangrijkste doel elke patiënt en cliënt die zorg te geven die hij nodig heeft en wel op een zo snel mogelijke wijze. Eén van onze uitgangspunten daarbij is de patiënt/ cliënt zo lang mogelijk in het eigen sociale netwerk te laten functioneren. De Zorggroep Suydevelt bestaat uit een aantal intramurale zorginstellingen: een ziekenhuis, een verpleeghuis, verschillende woon- en zorgcentra en een gespecialiseerde zorginstelling. Binnen de totale Zorggroep Suydevelt werken ca. 3400 medewer-

Uw schriftelijke sollicitaties kunt u binnen 4 weken na het verschijnen van deze advertentie richten aan Zorggroep Suydevelt, de heer P.N.Th.M. Windt, voorzitter Raad van Bestuur, Postbus 30002, 7800 RA Emmen.

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WORKSHOP L O N G S PA R E N D E B E A D E M I N G

Theoretische en praktische cursus beademenen

Datum: 2 november 2006 Voor meer informatie over de workshop kunt u contact opnemen met Mw. L.E. Haan, telefoon (020) 444 3697 of e-mail: [email protected].

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Editorial Board of the Netherlands Journal of Critical Care A.B. Johan Groeneveld, Editor in Chief Dept. of Intensive Care Medicine VU University Medical Center PO box 7057 1007 MB Amsterdam Arthur van Zanten, Managing Editor Dept. of Intensive Care Medicine Gelderse Vallei Hospital PO box 9025 6710 HN Ede

Kees Polderman, Internet Editor/ Section Editor Neuro Dept. of Intensive Care Medicine VU University Medical Center PO box 7057 1007 MB Amsterdam

Jan Bakker, Section Editor Hemodynamics Dept. of Intensive Care Medicine Erasmus Medical Center Rotterdam PO Box 2040 3000 CA Rotterdam

Armand Girbes, Section Editor General Dept. of Intensive Care Medicine VU University Medical Center PO box 7057 1007 MB Amsterdam

Johan Damen, Section Editor Anesthesiology Dept. of Cardiothoracic Anesthesiology and Intensive Care Medicine “Isala Klinieken”, location “Weezenlanden” Groot Weezenland 20/28 8011 GM Zwolle

Jan Hazelzet, Section Editor Pediatrics Pediatric Intensive Care Unit; Sophia Children’s Hospital; Erasmus Medical Center Rotterdam PO Box 2060 3000 CB Rotterdam

Paul van den Berg Dept. of Intensive Care Medicine Leids University Medical Center PO Box 9600 2300 RC Leiden

Anton van Kaam Dept. of Neonatal Intensive Care Emma Children’s Hospital Academic Medical Centre University of Amsterdam, Meibergdreef 9 1105 AZ Amsterdam

Alexander Bindels Dept. of Internal Medicine Catharina Hospital Michelangelolaan 2 5623 EJ Eindhoven Reinier Braams Dept. of Intensive Care Medicine University Medical Center Utrecht PO Box 85500 3508 GA Utrecht Can Ince Dept. of Physiology Academic Medical Center, University of Amsterdam Meibergdreef 9 1105 AZ Amsterdam

Hans van der Hoeven, Section Editor Mechanical Dept. of Intensive Care Medicine UMC St. Radboud PO Box 9101 6500 HB Nijmegen

Jozef Kesecioglu Division of Perioperative Medicine and Emergency Care, Cardiothoracic and Neurosurgical Intensive Care University Medical Center Utrecht Mail stop E03-511; PO Box 85500 3508 GA Utrecht Michael Kuiper Dept. of Intensive Care Medicine Medical Center Leeuwarden PO Box 888 8901 BR Leeuwarden

Peter van der Voort, Correspondence Editor Dept. of Intensive Care Medicine Medical Center Leeuwarden PO Box 888 8901 BR Leeuwarden

Evert de Jonge, Section Editor Scoring and quality assessment Dept. of Intensive Care Medicine Academic Medical Center, University of Amsterdam Mail stop G3-206 Meibergdreef 9 1105 AZ Amsterdam Heleen Oudemans-van Straaten, Section Editor Nephrology Dept. of Intensive Care Medicine Onze Lieve Vrouwe Gasthuis PO Box 95500 1090 HM Amsterdam

Peter Pickkers, Section Editor Sepsis and inflammation Dept. of Intensive Care Medicine UMC St. Radboud PO Box 9101 6500 HB Nijmegen Dick Tibboel, Section Editor Pediatrics Pediatric Intensive Care Unit; Sophia Children’s Hospital; Erasmus Medical Center Rotterdam PO Box 2060 3000 CB Rotterdam

Andrew Maas Dept. of Neurosurgery Erasmus Medical Center Rotterdam PO Box 2060 3000 CB Rotterdam

Peter Spronk Dept. of Intensive Care Medicine Gelre Hospital, location Lukas PO Box 9014 7300 DS Apeldoorn

Manu Malbrain Dept. of Intensive Care Medicine Academic Hospital Stuivenberg Lange Beeldekenstraat 267 B-2060 Antwerpen, Belgium

Tjip van der Werf Intensive and Respiratory Care Unit Dept. of Internal Medicine Groningen University Hospital PO Box 30001 9700 RB Groningen

Gerrit-Jan Scheffer Dept. of Anaesthesiology UMC St. Radboud PO Box 9101 6500 HB Nijmegen Marcus Schultz Dept. of Intensive Care Medicine Academic Medical Center, University of Amsterdam Mail stop G3-206 Meibergdreef 9 1105 AZ Amsterdam



Saskia Peerderman, Section Editor Neuro Dept. of Neurology Intensive Care VU University Medical Center PO box 7057 1007 MB Amsterdam

Durk Zandstra Dept. of Intensive Care Medicine Onze Lieve Vrouwe Gasthuis PO Box 95500 1090 HM Amsterdam

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16-08-2006 12:23:43

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Productinformatie Samenstelling en farmaceutische vorm: Pantozol ® 20 en Pantozol ® 40 maagsapresistente tabletten bevatten respectievelijk 22,6 mg en 45,1 mg pantoprazolnatriumsesquihydraat overeenkomend met respectievelijk 20 mg en 40 mg pantoprazol. Indicaties: Pantozol ® 20: onderhoudsbehandeling bij refluxoesofagitis, behandeling milde refluxziekte en daaraan gerelateerde symptomen, preventie van ulcera bij chronisch NSAID-gebruik. Pantozol ® 40: eradicatie van Helicobacter pylori in combinatie met twee geschikte antibiotica, ulcus duodeni, ulcus ventriculi en/of matige tot ernstige refluxoesofagitis, Zollinger-Ellison syndroom (ZES) en andere aandoeningen die gepaard gaan met pathologische hypersecretie. Dosering: Afhankelijk van de indicatie éénmaal daags één tablet Pantozol ® 20 of Pantozol ® 40. On demand gebruik van Pantozol ® 20 is mogelijk wanneer symptoomverlichting is bereikt. Doseerschema voor eradicatietherapie is opvraagbaar. Bij leverfunctiestoornissen maximaal 20 mg per dag. Ouderen en patiënten met verslechterde nierfunctie maximaal 40 mg pantoprazol per dag (met uitzondering van eradicatietherapie). Voor ZES: starten met 80 mg per dag, daarna aanpassen aan de klinische behoefte, tijdelijke verhoging boven 160 mg is mogelijk. Contra-indicaties: Overgevoeligheid voor pantoprazol of andere bestanddelen. De combinatietherapie voor eradicatie van Helicobacter pylori niet bij patiënten met matig tot ernstige nierof leverfunctiestoornissen. Waarschuwingen: Maligniteiten dienen uitgesloten te worden in verband met mogelijke maskering. Over gebruik bij kinderen zijn geen gegevens bekend. Bij patiënten met ernstige leverfunctiestoornissen moeten regelmatig leverenzymwaarden bepaald worden tijdens langdurige behandeling. Interacties: pH-afhankelijke absorptie van stoffen kan worden beïnvloed. Er zijn geen interacties waargenomen met antacida, carbamazepine, cafeïne, diazepam, diclofenac, digoxine, ethanol, glibenclamide, meto prolol, naproxen, nifedipine, piroxicam, fenytoïne, theofylline en orale contraceptiva. Daarnaast zijn er geen klinisch relevante interacties met metronidazol, amoxicilline en claritromycine. In de postmarketing periode is een aantal geïsoleerde gevallen van toename van INR-tijd waargenomen bij gelijktijdig gebruik met fenprocoumon en warfarine. Monitoring van de prothrombinetijd / INR wordt aanbevolen bij patiënten die behandeld worden met anticoagulantia uit de coumarinederivatengroep, na initiatie, beëindigen of gedurende onregelmatig gebruik van pantoprazol. Zwangerschap en borstvoeding: Er zijn onvoldoende gegevens bekend. Rijvaardigheid: Pantozol ® heeft geen invloed op de rijvaardigheid of het vermogen machines te bedienen. Bijwerkingen: Vaak maagdarmklachten en hoofdpijn. Soms allergische huidreacties, jeuk, duizeligheid en visusstoornissen. Zelden artralgie en droge mond. In enkele gevallen perifeer oedeem, leverbeschadiging, koorts, myalgia, leukopenie, thrombocytopenie, depressie, interstitiële nefritis en anafylactische reacties. Overige informatie: Verpakkingsgrootte: blisterverpakkingen met 15 of 30 tabletten en E.A.V. verpakking 50 stuks. Kanalisatie: UR. Vergoedingsstatus: volledig vergoed. Volledige informatie op aanvraag beschikbaar. Pantozol ® 20 RVG 23513; Pantozol ® 40 RVG 18300. (Augustus 2005)

WT bijsl 90x125

12-05-2006

08:46

Pagina 1

Tijd en energie over? De Intensivisten-pool!

Nederland heeft voorlopig nog een tekort aan intensivisten. Veel ziekenhuizen proberen er het beste van te maken, maar kunnen de zorg op hun IC afdeling niet altijd op het gewenste niveau leveren. Er wordt aan gewerkt, maar vooralsnog is er vraag naar intensivisten met interesse, tijd en energie om de nood te lenigen. ViaMedica is een gerenommeerd intermediair voor medisch specialisten in elke discipline. Op IC gebied verzorgt ViaMedica werving

ALTANA Pharma bv, Postbus 31, 2130 AA Hoofddorp, www.altanapharma.nl

en selectie van vaste/interim medewerkers alsmede het onderhouden van een IC pool

Verkorte productinformatie Tygacil

met intensivisten die in overleg “losse”

Tygacil 50 mg poeder voor oplossing voor infusie. Samenstelling: Elke 5 ml flacon Tygacil bevat 50 mg tigecycline. Na reconstitutie bevat 1 ml 10 mg tigecycline. Indicatie: Tygacil is geïndiceerd voor de behandeling van gecompliceerde huidinfecties en infecties van weke delen en voor de behandeling van gecompliceerde intra-abdominale infecties. Er dient rekening gehouden te worden met de officiële richtlijnen over het juiste gebruik van antibacteriële middelen. Contra-indicaties: Overgevoeligheid voor het actieve bestanddeel of voor één van de hulpstoffen. Patiënten die overgevoelig zijn voor tetracycline-klasse antibioticakunnen overgevoelig zijn voor tigecycline. Waarschuwingen/voorzorgsmaatregelen: Tigecycline kan dezelfde bijwerkingen als tetracycline-klasse antibiotica hebben. Er is beperkte ervaring met het gebruik van tigecycline voor de behandeling van infecties bij patiënten met ernstige onderliggende aandoeningen. Daarom is voorzichtigheid geboden bij het behandelen van zulke patiënten. Het gebruik van antibacteriële combinatietherapie dient steeds overwogen te worden wanneer tigecycline zal worden toegediend bij ernstig zieke patiënten met gecompliceerde intraabdominale infecties die secundair zijn aan een klinisch manifeste, intestinale perforatie of patiënten met beginnende sepsis of shock. Patiënten die cholestase vertonen moeten nauwkeurig gecontroleerd worden. Protrombinetijd of een andere geschikte anticoagulatietest dient gebruikt te worden om patiënten te controleren als tigecycline samen met anticoagulantia wordt toegediend. Pseudomembraneuze colitis is gemeld bij bijna alle antibacteriële geneesmiddelen en kan in ernst variëren van mild tot levensbedreigend. Het is daarom belangrijk deze diagnose te overwegen bij patiënten waarbij zich diarree voordoet tijdens toediening of nadat enig antibacterieel middel is toegediend. Het gebruik van tigecycline kan resulteren in overmatige groei van niet-gevoelige , waaronder schimmels. Patiënten dienen nauwkeurig gecontroleerd te worden gedurende de therapie. Als superinfectie optreedt, dienen passende maatregelen genomen te worden. Tygacil dient niet te worden gebruikt bij kinderen jonger dan 8 jaar vanwege het risico op verkleuring van de tanden en het wordt niet aanbevolen bij adolescenten jonger dan 18 jaar vanwege het gebrek aan gegevens met betrekking tot veiligheid en effectiviteit bij die leeftijdsgroep. Bijwerkingen: In klinische studies, waren de meest voorkomende, aan het geneesmiddel gerelateerde uit de behandeling voortkomende bijwerkingen reversibele misselijkheid en braken, wat gewoonlijk vroeg voorkwam (op behandelingsdagen 1-2) en over het algemeen mild tot matig in hevigheid was. Andere bijwerkingen die voorkwamen waren abcessen, infecties, sepsis/septische shock, verlengde geactiveerde partiële tromboplastinetijd (aPTT), verlengde protrombinetijd (PT), duizeligheid, flebitis, tromboflebitis, diarree, acute pancreatitis, verhoogd aspartaat-aminotransferase (AST) in serum en verhoogd alanine-aminotransferase (ALT) in serum, bilirubinemie, pruritus, uitslag, hoofdpijn, buikpijn, dyspepsie, anorexie, verhoogd amylase in het serum, verhoogd ‘blood urea nitrogen’ (BUN). Registratiehouder: Wyeth Europa Ltd., Verenigd Koninkrijk. U.R. April 2006

waarnemingen doen op andere ICU afdelingen in Nederland. Voor deze pool zoekt ViaMedica intensivisten die worden aangesproken door: •

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Uitstekende verdiensten

•

Nieuwe mensen ontmoeten in een

andere “keuken”

andere omgeving •

Direct in de patiëntenzorg werkzaam en geen bestuurlijke problemen

•

Na de dienst naar huis…

Heeft u interesse om in de ViaMedica IC pool te worden opgenomen dan kunt een email met uw CV sturen naar: [email protected]. Voor meer informatie kunt u bellen met dr. Nine van der Vange, 035-524 78 26

Voor de volledige SmPC zie wyeth.nl Conform de gedragscode van de CGR is dit promotiemateriaal uitsluitend bestemd voor artsen en apothekers. Wyeth Pharmaceuticals bv Postbus 255, 2130 AG Hoofddorp, www.wyeth.nl

06.tyg.6.8.

Leading the way to a healthier world


16-08-2006 12:23:46


Information for authors The Netherlands Journal of Critical Care (Neth J Crit Care) is the official journal of the Dutch Society of Intensive Care (‘Nederlandse Vereniging voor Intensive Care-NVIC’). Reports of research related to any aspect of the field of intensive care, whether laboratory, clinical, or epidemiological, will be considered for publication in Neth J Crit Care. All manuscripts will be subject to an independent reviewing process managed by the executive board.

Major Articles. Major articles report the results of original investigations that have been brought to an acceptable degree of completion. They should contain a maximum of 4,000 words and 50 references. Manuscript should be clear in outline (with subheadings) for maximum clarity. There is no fixed limit to the number of figures and tables; However, duplication of data from the text of the manuscript should be avoided. The first page of the manuscript should include: The title of the article, the names of all authors, footnotes to the title, complete address of all authors with identification of the corresponding author, and running title (for page heading). The text should contain the following sections: an Abstract, Introduction, Materials and Methods, Results, Discussion and Conclusion. An abstract should not exceed 250 words. In addition, writers are encouraged to write one or more short key-messages. For major articles the abstract should be divided into the following sections: Objective - Setting and Patients – Interventions - Measurements and Main Results - Conclusions.

(Systemic) reviews. Review articles are usually submitted after prior consultation with the editors, and are subject to the peer review process. They should contain a maximum of 4,000 words and 50 references. Systemic reviews should be focused: state the question to be addressed, the methods by which potential materials (original articles, published and unpublished abstracts, etc) have been selected, and the methods through which they are subsequently appraised. The text should contain an Abstract, Introduction, Search Results, Discussion and Conclusion section. An abstract should not exceed 250 words. For reviews it should be divided into the following sections: Objective - Search strategy – Summary of findings - Conclusions.

Editorials. Editorials may deal with any aspect of intensive care medicine. They are generally invited, but occasionally unsolicited editorials may be considered.

Clinical notes, images in intensive care medicine, and case reports Clinical notes should describe a specific intensive care medicine-related entity; images in intensive care medicine are photographic pictures in intensive care medicine, noteworthy for their scientific, emotional and/or challenging content; case reports are short presentations on cases that merit special attention. Clinical notes, images in

intensive care medicine, and case reports should include an abstract and must be limited to no more than 2000 words of text, a maximum of two inserts (tables or figures), and 15 references. In addition, writers are encouraged to write one or more short key-messages

Letters. Only correspondence submitted in reference to a previous publication in NJCC will be considered. Letters should be submitted within 8 weeks of publication of the paper to which it refers. Please prepare the letter in manuscript format, including a title page. Letters are limited to a maximum of 500 words of text, one table or figure, and a maximum of 5 references.

Guidelines. Guidelines, which are produced by the NVIC guideline committee (‘commissie richtlijnontwikkeling’) will be published in our Journal. Guidelines are usually preceded by a review on the topic of the guideline; these reviews should be in English, and are subject to the peer review process. Guidelines themselves will be published in both English and Dutch.

General information. Manuscripts should be submitted by e-mail (as attachments) to: [email protected]. The manuscript should be accompanied by a cover letter stating the following: the complete mailing address, E-mail address, telephone number and fax number of the corresponding author. Receipt of the manuscript will be acknowledged by E-mail within 14 days. If this should not be the case, authors are requested to check with the editor. Please submit your manuscript as a Word Perfect® or Microsoft Word® text-file. The language of the journal is English. Authors who are not fluent in the Englsih language should have their manuscript checked by a native English speaker. Tables. Tables should be numbered independently of the figures, with Arabic numerals, with headings, and kept separate from the text.

Figures. Figures should also be numbered using

be considered for publication, except for review articles, provided written permission from the original authors has been obtained and the source is clearly indicated. Colour figures are encouraged. Short, clear legends make additional description in the text unnecessary. The preferred location for figures and tables may be marked in the margins of the manuscript sheets. During the final lay-out process these remarks will be taken into account.

References. Only articles cited in the text should be listed. These should be arranged in order of appearance in the text […] and numbered sequentially. Only the reference number should appear in the text. The maximum number of listed authors is six; if there are more than six authors please list the first six and add et al. Article in journals: Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709. Books or book-sections: Thijs LG. Fluid therapy in septic shock. In: Sibbald WJ, Vincent JL (eds) Clinical trials for the treatment of sepsis. (Update in intensive care and emergency medicine, volume 19). Berlin Heidelberg New York, Springer 1995: pp 167-190.

Proofs. The corresponding author will receive

proofs by E-mail as a pdf-file (Adobe®-Acrobat®file). Corrected proofs must be returned by fax within 48 hours of receipt.

Production process. Decisions of the editors are final. All materials accepted for publication are subject to editing. The original manuscript will be discarded one month after publication unless the author requests the return of these original materials. The Neth J Crit Care reserves the right to edit manuscripts to conform to the journal style, and to improve clarity, precision of expression, and grammar. Authors may review these changes at the proof stage, but should limit any alterations in the proofs to correction of errors and clarification of misleading statements.

Arabic numerals, and kept separate from the text. Legends should be provided on a separate sheet. Schematic line drawings are preferred. Figures previously published elsewhere will generally not



477

16-08-2006 12:23:48

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VU medisch centrum is een universitair medisch centrum met nationale en internationale functies op het gebied van patiëntenzorg, onderwijs/opleiding en onderzoek. Er werken circa 6000 mensen.

Intensieve zorg begint met intensieve betrokkenheid

VU medisch centrum neemt als koploperziekenhuis deel in het VWSkwaliteitsprogramma ‘Sneller Beter’. Het wetenschappelijk onderzoek staat in de top 3 van de UMC’s en is georganiseerd in onderzoekinstituten: oncologisch/immunologisch, neurowetenschappelijk, cardiovasculair en extramuraal geneeskundig onderzoek. Met de faculteit Bewegingswetenschappen en ACTA vindt onderzoek plaats rond het thema ‘bewegen’. Het onderwijs en de opleidingen worden aangestuurd door een onderwijsinstituut en een opleidingscentrum.

VU medisch centrum. Kennis maakt ons beter.

Intensivist De afdeling Intensive Care Volwassenen beschikt over 28 niveau-III en 9 medium care-bedden. Naast patiëntenzorg zijn onderzoek en onderwijs belangrijke taken. De afdeling beschikt over opleidingsbevoegdheid voor het aandachtsgebied intensive care geneeskunde. Bij deze afdeling is, wegens het vertrek van een van de stafleden, een stafplaats vacant. U bent medisch specialist en (bijna) in het bezit van de GIC aantekening intensive care. Naast ruime ervaring in de patiëntenzorg, hebt u belangstelling voor en aantoonbare kwaliteiten in onderzoek en/of onderwijs. Een afgeronde promotie strekt tot aanbeveling. Wij bieden u een afwisselende functie bij een goed gestructureerde, dynamische afdeling met ruime wetenschappelijke output en alle mogelijkheden om u verder te ontplooien. Er wordt structureel ruimte geboden voor het doen van wetenschappelijk onderzoek. Gezien de samenstelling van de staf gaat de voorkeur uit naar een anesthesioloog-intensivist.

Voor meer informatie: prof. dr. A.R.J. Girbes, hoofd van de afdeling, en drs. R.J.M. Strack van Schijndel, plaatsvervangend hoofd van de afdeling; u kunt hen via het secretariaat bereiken, telefoon (020) 444 39 24.

Uw schriftelijke sollicitatie met cv stuurt of mailt u binnen twee weken naar VU medisch centrum, t.a.v. mevrouw C. Hoogenes, onder vermelding van vacaturenummer I4.2006.00037 op brief en envelop of als onderwerp van uw e-mail. VU medisch centrum, Postbus 7057, 1007 MB Amsterdam. E-mail: [email protected]. Voor meer informatie: www.VUmc.nl.

VUMED6024 176x228 Intensivist.in1 1 NJCC_04 binnenwerk 01.indd 478

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55:36 PM

n eth e rlan ds jou rnal of critical care Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved.

Received April 2006; accepted in revised form June 2006

c a s e

r e p o rt

Local toxicity of potassium chloride B.L. Hübner Department of Intensive Care, University Hospital Maastricht

Abstract. A 64 year-old female intensive care patient was accidentally given a concentration of 1 mmol/ml potassium chloride into a peripheral venous infusion in the dorsum of the left foot at a rate of 120 mmol/24 hours. Three hours after the start of the infusion, the patient developed an extensive but painless thrombophlebitis of her lower leg with involvement of the surrounding tissues and with blisters of the skin. Within a few weeks, the abnormalities disappeared spontaneously. This case report details the severe local toxicity of highly concentrated potassium fluid infusion.

Case history A 64 year-old female patient with a history of severe arterial occlusive disease was admitted to the Intensive Care Unit after she had twice undergone an emergency laparotomy for bleeding complications caused by elective abdominal aneurysm repair one day earlier. With the patient’s clinical condition rapidly improving, the endotracheal tube and central venous catheter were removed within hours of arrival. She received intravenous potassium chloride at a concentration of 1 mmol/ml and a rate of 120 mmol/24 hours to treat hypokalaemia. Originally, potassium chloride was given through the central venous catheter, but after removal of this device, all fluids and medications were transferred to peripheral venous catheters. Unintentionally, potassium chloride was likewise given at an unchanged dosage and concentration through a peripheral venous catheter in the dorsum of her left foot. Approximately three hours after peripheral potassium supplementation had been started, extensive skin abnormalities arose proximally to the infusion site. A conspicuous thrombophlebitis was present with involvement of the surrounding tissues including the skin (Figure 1). Blisters had formed around the entire venous flow tract of the lower leg which gave it the appearance of a burn.. Although the patient was fully awake, cooperative, and not under epidural analgesia, she did not report any pain. After the abnormalities were discovered, the intravenous catheter involved was immediately removed. Several weeks after this incident the skin changes have fully disappeared without specific treatment.

Discussion Medication errors involving potassium are among the most common avoidable causes of fatalities in emergency medicine [1]. It is also well known that supplementation of high dosages of potassium given through peripheral veins may have serious complications [2]. Hospital protocols and medical textbooks recommend strict limitations on potassium dosages and concentrations. Concentrated potassium chloride, containing 1 or 2 mmol/ml, is unsuitable for peripheral injection. Dilutions containing less than 0.1 mmol/ml of potassium chloride, and rates of infusion not exceeding 10-20 mmol/hour, are commonly advised [3]. This case, in which the concentration, rather than the total rate of infusion, was higher than recommended, highlights one of the risks involved with undiluted potassium solution. If administration had lasted longer, it is likely Correspondence: BL Hübner Email: [email protected]

Figure 1. Toxicity of potassium solution and injury of greater saphenous vein and overlying tissue.

that the tissue injuries would have been even more severe or even irreversible. Extravasation of potassium is another known cause of local tissue injury. In this case, extravasation seems unlikely because the skin abnormalities were distributed in parallel to the anatomical tract of the saphenous vein. Parenteral drug toxicity is often accompanied by complaints of painfulness on injection. In this case, it is demonstrated that even without pain, serious injury can occur. In English speaking countries, various quality and safety campaigns promoting the safe use of potassium by healthcare workers have been established [1, 4, 6]. In the Netherlands, such programmes do not yet exist: however, it is likely that focusing attention on this subject may improve safety. References 1. Joint Commission on Accreditation of Healthcare Organizations (homepage on the internet). Available from: http://www.jcaho.org/ (cited 2006 Mar 20) 2. Oh M.S., Carroll H.J.. Electrolyte and Acid-Base Disorders. In: Chernow B. (ed) The Pharmacologic Approach to the Critically Ill Patient. 3rd Edition. Baltimore, Williams and Wilkins, 1994: pp 962-3 3. Burger C.M.. Hypokalemia: Averting crisis with early recognition and intervention. Am J Nursing 2004 Nov;104(11):61-5. 4. National Patient Safety Agency. (homepage on the internet). Available from: http:// www.npsa.nhs.uk/ (cited 2006 Mar 20) 5. Medication Safety Taskforce of the Australian Council for Safety and Quality in Health Care. (homepage on the internet). Available from: http://www.safetyandquality.org/ index.cfm (cited 2006 Mar 20) 6. Institute for Safe Medication Practices Canada. (homepage on the internet). Available from: http://www.ismp-canada.org/ (cited 2006 Mar 20)



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c a s e

Received December 2005; accepted in revised form June 2006

r e p o rt

A case of mannitol-induced hyponatraemia, renal failure and respiratory insufficiency I.A. Meynaar1, P.L. Tangkau1, B.C. Verdouw1,2, M. Wagemans2, L. Dawson1, E.F. Salm1, F. Borst3 From the Intensive Care Unit (1), the Department of Anaesthesia (2) and the Department of Nephrology (3), Reinier de Graaf Hospital, Delft, Netherlands

Abstract. We describe a patient with mannitol-induced hyponatraemia, renal insufficiency and respiratory failure. Mannitol is mostly used as an osmotic agent for the treatment of intracranial hypertension, but can also be used as a radical scavenger in the treatment of complex regional pain syndrome. Mannitol toxicity can manifest itself by two distinct clinical pictures. Osmotic diuresis induced by mannitol can result in volume depletion and hypernatraemia. On the other hand, if mannitol is retained by the kidneys this results in oliguric renal insufficiency, volume overload and hyponatraemia. In the latter case, renal function can be restored only by removal of mannitol by haemofiltration or haemodialysis. To prevent mannitol toxicity careful monitoring of serum osmolality, serum sodium, serum creatinine and fluid balance are essential.

Case

Discussion

A 48-year-old woman, 97 kg, 158 cm, was admitted for treatment of complex regional pain syndrome type 2 (CRPS II), formerly known as reflex sympathetic dystrophy, of the left leg. She had previously been diagnosed with diabetes mellitus, hypertension, venous thromboembolism and brain stem infarction leaving her unable to walk and in a wheelchair. She had been treated for several pain syndromes over the previous 10 years and was a regular visitor at the pain clinic. At the time of admission she was taking phenprocoumon, omeprazol, tramadol, mebeverine, candesartan, sulpiride and metformin. The patient was admitted to the pain clinic on day 1 to be treated by a continuous intravenous infusion of mannitol 10%, 2000 ml daily as. Twelve days previously her serum sodium, potassium, urea and creatinine levels were normal (Table 1). No laboratory tests were done on the day of admission. On day 4 the patient complained of nausea and headache and subsequently started vomiting. She was awake and alert and she had no oedema, her blood pressure was 140/70 mmHg and her central venous pressure was normal. Her serum sodium was 112 mmol/L and creatinine was 370 µmol/L. The mannitol infusion was stopped. She was first treated with 100 ml of a 10% NaCl solution after which her sodium level rose to 116 mmol/L in 6 hours. Subsequently she was treated with 500 ml of a 2.5% NaCl solution over 12 hrs after which her sodium was 126 mmol/L and serum creatinine was 693 µmol/L. At that moment, on day 5, she became hypoxic with pulmonary oedema and a blood pressure of 150/90 mmHg. She was transferred to the ICU, where she was intubated and mechanical ventilation was started. Central venous pressure was 14 mmHg. Continuous venovenous haemofiltration (CVVH) was started. She was also treated by selective decontamination of the digestive tract, enteral nutrition, nitroglycerine and frusemide. On day 7, serum sodium was 136 mmol/L and serum creatinine was 143 µmol/L and CVVH was discontinued. On day 8, mechanical ventilation was stopped. She was transferred to the ward on day 9 and discharged home on day 15.

This case concerns a 48-year-old woman who developed hyponatraemia, pulmonary oedema and renal failure due to intravenous administration of mannitol for treatment of complex regional pain syndrome II. Mannitol is mostly used as a hypertonic solution for the treatment of intracranial hypertension. However, in the treatment of complex regional pain syndrome mannitol is used as a radical scavenger or antioxidant.1 In the past mannitol has been used for the treatment of glaucoma and for the prevention of nephrotoxic renal failure, [25] but these indications have virtually become obsolete [6, 7]. The administration of mannitol for intracranial hypertension is recommended by the Brain Trauma Foundation Guidelines [8]. Treatment of CPRS is largely based on physiotherapy and pain reduction and treatment with mannitol is only used as a last resort, and as it is not evidence-based, should probably be discouraged [1, 9, 10]. Mannitol therapy can result in two different kinds of metabolic derangement. Firstly volume depletion and hypernatraemia can occur since when mannitol acts as an osmotic diuretic, it results in loss of water and hypernatraemia [2-4, 11-15]. But if the kidneys fail to excrete and instead retain mannitol then plasma osmolality rises, resulting in osmotic movement of water from the intracellular compartment to the extracellular compartment and into the circulation, resulting in volume overload and dilutional hyponatraemia [2-4, 11-16]. Volume overload and hyponatraemia are aggravated by an increase in atrial natriuretic peptide (ANF) and antidiuretic hormone (ADH) [16]. The rise of plasma osmolality is reflected in the osmol gap, the difference between the calculated osmolality (plasma sodium x 2 + glucose + urea) and the measured osmolality. Fluid overload and hyponatraemia are aggravated by oliguria and renal insufficiency, which presumably develops because of renal vasoconstriction, swelling and vacuolization of tubular cells due to endocytosis and mannitol accumulation [2-4, 11-14]. This is mostly seen in patients with pre-existent renal insufficiency or when diuretics or nephrotoxic drugs are given concomitantly [4, 13]. In this patient, no diuretics or nephrotoxic drugs were given, but she did receive candesartan, an angiotensin II inhibitor. Her renal function as measured by serum creatinine and urea was normal before the event. Monitoring serum osmolality and stopping the mannitol infusion

Correspondence: IA Meynaar E-mail: [email protected]



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Table 1

Sodium (mmol/L) Potassium (mmol/L) Creatinine (µmol/L) Urea (mmol/L) Haemoglobin (mmol/L) Glucose (mmol/L) Measured Osmolality (mOsm/kg) Calculated Osmolality (2xNa + Gluc +Ur) Osmol gap (mOsm/kg) pH pCO2 (kPa) Act bic (mmol/L) BE (mmol/L) pO2 (kPa)

Reference Day–12

Day 4 8.00

Day 4 16.00

Day 5 9.00

Day 5 12.00

Day 5 20.00

Day 6 6.00

Day 7 6.00

137-145 3.6-5.0 60-110 2.5-7.0 7.3-9.8 3.5-6.0 280-300

112 4.4 370 8.2

116 4.9

126 5.5

128

9.1

10.1

8.0 308 249.1 58.9

8.0 336 270 65.9

126 4.9 693 11.4 7.0 9.9

7.28 4.4 16 -11.4 6.0

7.34 4.4 18 -8.0 15.3

136 3.3 422 8.9 6.5 8.0 311 289.9 22.1 7.45 4.1 22 -2.4 13.8

136 3.1 143 5.1 6.0 9.3 292 286.4 5.6 7.46 4.9 26 2.1 18.9

142 4.2 85 2.8 7.4

4.6

7.35-7.45 4.5-6.1 21-27 -5.0-5.0 10.0-13.3

when serum osmolality exceeds 320 mOsm/kg is mandatory to prevent mannitol- induced renal failure [8]. A recent study, however, did not confirm that this strategy prevents mannitol-induced renal failure [15]. The Brain Trauma Foundation recommends repeated boluses of mannitol rather than a continuous infusion and a maximum dose of 1 g/kg bodyweight while keeping serum osmolality below 320 mOsm/ kg.8 These guidelines do not specify how often the mannitol bolus may be repeated. In a study in healthy volunteers, mannitol had an elimination half time of 79 minutes.16 So it can be expected that the effect of a 0.5-1 g/kg mannitol bolus will taper off over a few hours. This is in agreement with clinical experience in traumatic brain injury where mannitol boluses are administered several times a day to treat intracranial hypertension and where the daily dose of mannitol will easily exceed 1 g/kg. This also implies that guidelines limiting mannitol bolus administration to 1 g/kg cannot be used simply to set the maximum dose of continuous infusion at 1 g/kg per day. There are no evidence-based guidelines for the use of mannitol in CPRS, but for this condition when it is used as a radical scavenger, mannitol should preferably be given by continuous infusion. The usual dose

Day 9 6.00

106 6.4

is 100-200 g/day [1, 5]. In our opinion mannitol should not be used as a first line of treatment in CPRS, but if it is used as a last resort, careful monitoring is mandatory. Monitoring should include laboratory investigations e.g. serum creatinine, serum sodium and serum osmolality, combined with clinical assessment, monitoring of fluid balance and a high degree of suspicion. This patient was treated with hypertonic saline to reverse the hyponatraemia. This must have aggravated fluid overload by attracting water from the intracellular compartment to the extracellular compartment and into the circulation, resulting in pulmonary oedema although hyponatraemia was indeed reversed. Treatment should instead be directed at removal of the mannitol rather than on the reversal of hyponatraemia only. In conclusion, this case illustrates that mannitol treatment should only be given in conjunction with careful monitoring of fluid balance, serum osmolality, serum creatinine and serum sodium, even in the absence of pre-existent renal insufficiency. However if fluid overload and oliguria develop, this can only be reversed by haemofiltration or dialysis.

References 1. Goris RJ. Treatment of reflex sympathetic dystrophy with hydroxyl radical scavengers. Unfallchirurg 1985;88(7):330-2. 2. Gadallah MF, Lynn M, Work J. Case report: mannitol nephrotoxicity syndrome: role of hemodialysis and postulate of mechanisms. Am J Med Sci 1995;309(4):219-22. 3. Horgan KJ, Ottaviano YL, Watson AJ. Acute renal failure due to mannitol intoxication. Am J Nephrol 1989;9(2):106-9. 4. Perez-Perez AJ, Pazos B, Sobrado J, Gonzalez L, Gandara A. Acute renal failure following massive mannitol infusion. Am J Nephrol 2002;22(5-6):573-5. 5. Warren SE, Blantz RC. Mannitol. Arch Intern Med 1981;141(4):493-7. 6. Solomon R, Werner C, Mann D, D’Elia J, Silva P. Effects of saline, mannitol, and furosemide to prevent acute

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7. 8. 9. 10. 11.

decreases in renal function induced by radiocontrast agents. N Engl J Med 1994;331(21):1416-20. Oudemans-van Straaten HM. Prevention of contrast nephropathy. NVIC Guideline 2005. www.nvic.nl. Brain Trauma Foundation. Guidelines for the treatment of traumatic brain injury 2000: www.braintrauma.org,. Rho RH, Brewer RP, Lamer TJ, Wilson PR. Complex regional pain syndrome. Mayo Clin Proc 2002;77(2):17480. Birklein F. Complex regional pain syndrome. J Neurol 2005;252(2):131-8. Sakemi T, Ikeda Y, Ohtsuka N, Ohtsuka Y, Tomiyoshi Y, Baba N. Acute renal failure associated with mannitol infusion and reversal with ultrafiltration and hemodialysis. Nephron 1996;73(4):733-4.

12. van Hengel P, Nikken JJ, de Jong GM, Hesp WL, van Bommel EF. Mannitol-induced acute renal failure. Neth J Med 1997;50(1):21-4. 13. Visweswaran P, Massin EK, Dubose TD, Jr. Mannitol-induced acute renal failure. J Am Soc Nephrol 1997;8(6):1028-33. 14. Weaver A, Sica DA. Mannitol-induced acute renal failure. Nephron 1987;45(3):233-5. 15. Gondim Fde A, Aiyagari V, Shackleford A, Diringer MN. Osmolality not predictive of mannitol-induced acute renal insufficiency. J Neurosurg 2005;103(3):444-7. 16. Ambuhl PM, Ballmer PE, Krahenbuhl S, Krapf R. Quantification and predictors of plasma volume expansion from mannitol treatment. Intensive Care Med 1997;23(11):1159-64.


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Received November 2005; accepted in revised form June 2006

r e v i e w

Subarachnoid haemorrhage: a disorder requiring multidisciplinary intensive care C. Hoedemaekers1, J. De Vries2, T. van der Vliet3, F.E. De Leeuw4, P.E. Vos4, J.H. van der Hoeven1 Radboud University Nijmegen Medical Centre, Departments of Intensive Care1, Neurosurgery2, Radiology3 and Neurology4.

Abstract. Objective: To provide an update on the pathophysiology, current state of monitoring in the intensive care unit and therapeutic options in patients with subarachnoid haemorrhage. Search strategy: Articles in the PubMed database were searched using the MESH keywords: Subarachnoid Hemorrhage, INTRACRANIAL ANEURYSM, VASOSPASM, INTRACRANIAL, BRAIN ISCHEMIA, CEREBRAL INFARCTION, Endovascular treatment. Summary of Findings: Knowledge of the pathophysiology of subarachnoid haemorrhage and subarachnoid haemorrhage-related vasospasm has increased over the past decade. The endothelium and the immune system have important parts to play and new treatment options based on pathophysiology appear promising. Endovascular treatment has assumed an important role in the obliteration of the aneurysm. Results from the ISAT trial comparing endovascular with surgical treatment support the use of coiling in a subgroup of patients. Conclusions: Although in recent years progress has been made, large prospective randomized trials are still necessary to develop the optimal treatment for patients with SAH. Effective treatment following SAH requires dedicated teamwork from intensivists, neurologists, neurosurgeons and intervention radiologists

Introduction

Pathophysiology

Subarachnoid haemorrhage [SAH] is a complex disease entity with a high mortality and morbidity. Although case fatality has slowly declined over the last three decades, it is still around 50% overall [1]. Approximately one-third of surviving patients remain supportdependent (on what?). In addition, these patients suffer from a large number of complications throughout the course of the disease such as acute cardiac dysfunction, pulmonary complications and metabolic derangement. Effective treatment of patients with a SAH requires dedicated teamworkfrom intensivists, neurologists, neurosurgeons and intervention radiologists. This review emphasizes the epidemiological and pathophysiological aspects of SAH, and current state of possible monitoring in the ICU. Re-bleed and vasospasm are the major causes of death and disability in patients who survive the initial episode of SAH. We focused on reviewing the options for treatment or prevention of these specific complications.

Epidemiology Recent studies have shown the incidence of SAH in Western Europe and North America to be 6-8/100.000/year [2]. Marked but unexplained regional differences exist with higher incidences in Finland and Japan compared to the rest of the world [22 and 23/100.000/year respectively]. The incidence of SAH increases with age 3 and women are at a 1.6 [95% CI 1.5-2.3] times higher risk than men. The major risk factors for the development of SAH are a first degree relative with SAH, hypertension, smoking and the use of more than 2 units alcohol/day [1, 2, 4].

Correspondence: C Hoedemaekers Email: [email protected]

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Aneurysm

SAH is most frequently [85%] caused by rupture of a saccular aneurysm originating from the wall of an intracerebral artery, and a small number of cases are due to perimesencephalic haemorrhage [10%] and a variety of other rare aetiologies [5%] [5]. The prevalence of saccular aneurysm in the general population is 2-5%, based on autopsy series, and increases with age. Saccular aneurysms usually arise at or close to the bifurcation of the main intracranial arteries. The majority are located within the anterior cerebral circulation, with 40% located in the internal carotid artery, 30% in the region of the anterior communicating artery and 20% in the proximal divisions of the middle cerebral artery. A minority of the aneurysms [5-10%] are located in the posterior cerebral or vertebrobasilar arteries [6]. Bleeding is caused by disruption of the extra cellular matrix of the arterial wall, and associated with a decreased number of structural proteins in this matrix including collagen type 3 and 4 and elastin [7]. It remains uncertain if this decrease is due to decreased synthesis of these proteins or to accelerated protein degradation [8]. Less frequently, haemorrhage may be caused by trauma, arteriovenous malformations/fistulae, vasculitides, intracranial arterial dissections or amyloid angiopathy. Vasospasm

Delayed cerebral ischaemia [DCI], caused by severe vasospasm, is the leading cause of morbidity and mortality in patients who survive the initial SAH. As many as 70% of patients show angiographic vasospasm from 4 to 12 days after SAH [9, 10]. Complex multifactorial pathogenic pathways are probably responsible for cerebral vasospasm after SAH. The exposure of cerebral blood vessels to blood products such as oxyhaemoglobin, is known to be a potent inducer


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of vasospasm [11]. More recent studies in both rodents and humans suggest that the endothelium plays an important role in the induction of vasospasm, including impaired endothelium-dependent relaxation, increased production of endothelial derived constriction factors, and impaired potassium channel activity [12]. Endothelin-1 [ET-1], a potent endothelium-derived vasoconstrictor plays an important role in the development of vasospasm and DCI. ET-1 can be released upon stimulation by thrombin and oxyhaemoglobin, which are both present in the subarachnoidal space after SAH [13, 14]. In patients with cerebral vasospasm the concentration of ET-1 in brain parenchyma and cerebrospinal fluid is increased [15, 16]. In a recently published multicentre phase II trial, clazosentan, an ET-A receptor antagonist significantly reduced the frequency and severity of cerebral vasospasm following severe aneurysmal SAH [17]. SAH induces an inflammatory response and this is another potential mechanism leading to cerebral vasospasm. The inflammatory process includes both cellular and humoral immunity. Within 2448 hours after SAH, inflammatory cells appear in the subarachnoid space and in large spastic arteries [18-20]. Cytokines are powerful mediators and regulators of immune responses. IL-6 and IL-8 are increased in cerebrospinal fluid in patients with SAH [21]. Fassbender et al showed that the release of IL-1β, TNFα and IL-6 in the subarachnoidal space of patients with SAH was associated with the development of increased flow velocities as measured by transcranial Doppler [22]. In these experiments, cerebrospinal fluid concentrations of IL-6 were significantly increased in patients with a poor clinical outcome. Diagnosis

The diagnosis is initially missed in 12-51% of SAH patients [23], most likely due to an atypical presentation. In classic cases, patients with SAH present with a history of an unusually severe headache [“worst pain ever”] that develops within seconds. Loss of consciousness is found in approximately half of the patients presenting with SAH, but may also occur in patients with thunderclap headache [24]. Other features equally unhelpful in making this distinction are vomiting, a history of previous attacks, seizures or double vision. One-third of patients presenting at the emergency department with SAH have focal neurological deficits but these do not help to distinguish between SAH and other acute neurological disorders. CT scanning is usually the first line investigation in most patients with suspected SAH and typically shows hyperdense extravasated blood in the subarachnoid space (Figure 1) [25]. The sensitivity of the CT in detecting SAH is time-dependent. If undertaken within 1-2 days after the ictus the sensitivity is approximately 95%, thereafter it shows a gradual decline with a sensitivity of 85% after 5 days, 50% after one week and almost zero after 3 weeks [26]. In patients with suspected SAH and a negative CT, lumbar puncture is the next step in the diagnosis of SAH and relies on detection of xanthochromia by spectrophotometry. To avoid formation of oxyhaemoglobulin in vitro, the specimens of cerebrospinal fluid should be immediately centrifuged and stored in the dark. The sensitivity of CSF spectophotometry in diagnosing SAH in patients with a compatible history is high, (in a recent retrospective analysis as high as100% ) although with a lower specificity than previous studies [27-29]. Conventional angiography is still considered the gold standard for detecting aneurysms in patients with SAH. A meta-analysis of prospective trials studying the complication rate of angiography in SAH patients revealed a 1.8% risk of transient or permanent neuro-

logical complications [30]. Other imaging modalities such as MR and CT angiography are increasingly being used in these patients. Compared to classic angiography, the sensitivity of these techniques is between 69-100% and 85-98% respectively [31]. Intensive monitoring

Intensive monitoring and early intervention may prevent secondary brain damage. Key mechanisms involved include a) ischemia, excitoxicity and energy failure; b) neuronal death cascades; c) cerebral swelling and d) inflammation. Repeated clinical examination of the patient is an important diagnostic measure, but only recognizes neurological changes when the damage has already occurred. In addition, neurological examination in the ICU is limited due to the use of sedation and neuromuscular blocking agents. The overall aim of monitoring is to alert the clinician to decreases in brain tissue oxygenation before permanent damage has occurred. In general, brain tissue hypoxia can be caused by insufficient blood flow, hypoxaemia, increased intracranial pressure, vasospasm or increased metabolic demand. In 1982 transcranial Doppler sonography [TCD] was introduced as a non-invasive technique for monitoring flow velocities in basal cerebral arteries [32]. Good correlation between the measured flow velocities, angiographically documented vasospasm, and neurological status was reported. However, considerable discrepancies between flow velocity and the corresponding neurological status have been found. These include both increased flow velocities in the middle cerebral artery in patients without neurological deficits [false positive TCD] and severe neurological deficits in the presence of normal TCD values [false negative TCD] [33]. These discrepancies may be due to the definition of normal and pathological TCD values, or to interobserver variability. Prospective blind comparison of TCD with cerebral angiography of 22 patients with acute subarachnoid haemorrhage showed that a TCD mean velocity threshold of 160 cm/s accurately detects clinically relevant vasospasm [34]. EEG monitoring provides continuous information about cerebral function, is tightly linked to cerebral metabolism, sensitive to ischaemia and hypoxia and can detect neuronal dysfunction at a reversible stage [35]. EEG abnormalities arise when cerebral blood flow declines to 25-30 ml/100g/min but cell death does not occur above values of 10-12 ml/100g/min. This suggests that the EEG may be a valuable tool in recognizing secondary insults and offers an opportunity for early intervention. Using a quantitative EEG parameter [relative alpha-variability] derived from 8-12 hour’s continuous registration, investigators were able to diagnose vasospasm in all patients with angiographically documented vasospasm, and to detect ischaemia a mean of 2.9 days earlier than by using TCD or angiography [36]. Changes in alpha-delta ratio from short EEG segments [1 minute traces] are also a sensitive parameter for the detection of DCI in patients with poor grade SAH [37]. Using a cut-off value of more than 10% decrease in alpha-delta ratio in 6 consecutive traces, or a decrease of > 50% in any one trace had a sensitivity of 100% with a specificity of 76% for detecting DCI. Jugular bulb oximetry [SjbO2] can provide a global assessment of brain oxygen supply and utilization. Few studies have used SjbO2 measurements in patients with SAH although a small pilot study in patients suggests that SjbO2 may be helpful in predicting vasospasm [38]. Further research is necessary to determine the diagnostic relevance of SjbO2 in patients after severe SAH. Brain tissue PO2 monitoring [ptiO2] is an invasive tool to monitor



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tissue oxygenation in the area at risk using intraparenchymal oxygen sensitive microelectrodes. In patients post-SAH, ptiO2 is associated with the severity of the disease, the occurrence of ischaemic events and can predict a poor outcome of aneurysm surgery [39-41]. Its role in guiding therapy in the ICU has not been established. Bedside cerebral microdialysis is a relatively new monitoring tool to detect local metabolic changes in brain tissue. Brain ischaemia is characterized by increases in lactate, pyruvate, and the lactate/pyruvate ratio. In SAH patients with acute focal deficits, microdialysis values of lactate, lactate/pyruvate ratio, glutamate, and glycerol were significantly higher compared to controls [42]. More importantly, these neurochemical changes preceded clinical signs by between 0-20 hours. In SAH, glutamate was found to be the earliest marker of ischemia, followed over time by lactate, lactate/pyruvate ratio and glycerol [43]. Although intensive monitoring is frequently used in most neurological ICUs, its role in the prevention of secondary brain damage is not undisputed. Large randomized controlled trials showing improved outcome in patients with intensive monitoring are not available. In addition, a recent retrospective review of patients after traumatic brain injury in two different hospitals showed no improved outcome in patients treated according to a protocol based on strict ICP/CPP targets [44]. The ICP/CPP-targeted intensive care treatment even resulted in prolonged mechanical ventilation and increased use of sedatives, vasopressors, mannitol, and barbiturates.

surgery [i.e. within three days after SAH] tended to be better than late surgery. The difference, however was not significant [49]. Results of a retrospective observational study in 1500 patients in eight hospitals in the Netherlands found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor condition, however, neurological outcome after early surgery was significantly better [50]. Furthermore, early operation simplifies the prevention and treatment of vasospasm. Minimal invasive therapy in which a tiny microcatheter is navigated from the femoral artery into the cerebral blood vessels allows the placement of specially designed coils into the dome of the aneurysm [51]. Under X-ray guidance coils are packed into the aneurysm, filling up its volume and thereby preventing blood from entering, thus protecting the patient from bleeding. The ISAT trial showed that following coiling patients had a significantly better outcome after one year than did surgically-treated patients [52]. Complete angiographic obliteration of the aneurysm was documented in 66% of coiled patients, compared to 82% of patients after surgery. After one year of follow-up there was an absolute risk reduction of 7.4% for mortality and morbidity favouring endovascular treatment. The risk of epilepsy was substantially lower in patients allocated to endovascular treatment. Long-term follow-up shows that the re-bleed rate for the coiled patients was 0.2% per patient year with a mean follow-up of 4 years [53]. The major drawback of this study is the fact that 9559 patients were assessed for eligibility and only 2143 patients were enrolled based on subjective criteria, leaving 7416 who were not included for a number of reasons. In the latter group there were no significant differences in outcome between patients who had undergone the coiling and clipping procedures. . The majority of patients randomized into ISAT were patients with good clinical status (Hunt and Hess scale I-II), relatively small aneurysms (10 mm or smaller in diameter) localized in the anterior circulation [52]. Patients admitted to the ICU usually represent a more severe category of patients meaning that the results of the ISAT trial are not directly applicable to this group. Another drawback of the study is the relatively high rate of post-clipping, residual abnormalities and surgical mortality compared to other published series. Patients were admitted from 42 neurosurgical centres, but five large centres in the United Kingdom enrolled more than half of the patients. Since procedure volumes and experience directly affect outcome, this may have biased the results. Therefore, in a substantial number of patients the best treatment option is still open to debate and strongly depends on local institutional experience and availability of the treatment options. For patients in good clinical condition with ruptured aneurysms in either the anterior or posterior circulation, coiling is associated with a better outcome if both treatment options could be followed. [54].

Treatment

Prevention and treatment of vasospasm

Figure 1. CT scan of a patient with SAH showing blood in the subarachnoidal space.

Neurosurgical and endovascular treatment

The main preventable complication of SAH is re-bleeding, which is disabling or fatal in 80% of the patients. In the first few hours after admission for the initial SAH, up to 15% of patients have a sudden episode of clinical deterioration suggesting re-bleeding [45-47]. After day 0 the re-bleeding rate is 1.5% per day to a total of 27% at two weeks and 35-40% at four weeks [45, 48]. To prevent re-bleeding obliteration of the aneurysm as early as possible is warranted. In the only randomized controlled trial, early

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Current strategies in the management of cerebral vasospasm include the calcium-channel blocker nimodipine and hypertensive hypervolemic haemodilution therapy [“triple-H therapy”]. A recent Cochrane analysis of the literature reviewed the use of calcium antagonists and magnesium in the prevention and treatment of vasospasms after SAH [55]. Oral nimodipine reduced the risk of poor outcome with a relative risk of [RR] 0.70 [95% CI 0.58 to 084]. This positive effect of nimodipine is mostly due to one large study by Pickard et al., with other differences in the management of the treatment groups. There is no evidence that intravenous nimodipine or other calcium antago-


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nists improve outcome. Intravenous nimodipine is often used in the acute phase of SAH in the ICU, and can induce severe arterial hypotension. Since there is no evidence of efficacy, routine intravenous administration of nimodipine should be questioned and best avoided in case of hypotension. In experimental models of stroke and SAH magnesium sulphate has been shown to have a neuroprotective effect. Hypomagnesaemia occurs in more than 50% of patients with SAH and is related to the occurrence of DCI and poor outcome after 3 months [56]. Administration of magnesium sulphate within four days of SAH reduced the incidence of DCI, however, the results of this phase II trial were not statistically significant and need to be confirmed in a phase III trial [57]. Another, recently published phase II trial in SAH patients has shown that treatment with pravastatin ameliorates vasospasm, improves cerebral auto regulation and reduces DCI [58]. Although widely used, the efficacy of triple-H therapy has not been proven in large prospective randomized trials. Triple-H therapy was instituted after the publication of a small prospective trial reporting an improved outcome in 15 patients treated with fluid expansion instead of diuretics [59]. Results from a recent Cochrane review indicate that volume expansion therapy does not improve outcome nor the occurrence of secondary ischaemia [60]. Complications of tripleH therapy that have been reported in 10-20% of patients, include exacerbation of cerebral oedema, increased intracranial pressure and

pulmonary oedema [61]. Pathophysiological data support the use of inotropes in these patients. There is abundant sympathetic innervation of the cerebral vasculature [62]. Since cerebral autoregulation is frequently disturbed in patients with SAH, induced hypertension can result in altered cerebral blood flow velocities [63] and increased cerebral blood flow [64]. The use of phenylephrine to increase mean arterial pressure [MAP] results in increased cerebral blood flow velocities as measured by transcranial Doppler ultrasound [63]. Recent experiments in patients with vasospasm after SAH showed that increasing cardiac output without changes in MAP can elevate cerebral blood flow in ischaemic areas [65]. Further research is needed to support the widespread use of triple-H therapy. Currently, many other therapies are being investigated including magnesium sulphate, endothelin antagonists, and statins.

Conclusion The medical and surgical management of aneurysmal SAH has changed dramatically over the past few decades. Although new intensive monitoring techniques are becoming available, the value of these monitoring modalities in improving outcome still has to be assessed. New drugs in the treatment of cerebral vasospasm might substantially improve the prognosis. For a subgroup of patients, surgical treatment can be replaced by endovascular treatment.

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Received March 2006; accepted in revised form May 2006

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Electrical impedance tomography I. Frerichs, J. Scholz, N. Weiler Department of Anaesthesiology and Intensive Care Medicine, University Medical Centre of Schleswig-Holstein, Campus Kiel, Kiel, Germany

Abstract. Electrical impedance tomography (EIT) is a relatively new medical imaging modality with the potential to become a bedside monitoring tool for intensive care patients. It is anticipated that EIT will optimize ventilator therapy due to its capacity to determine changes in regional lung aeration and ventilation over time. The use of EIT for imaging pulmonary perfusion-related impedance changes is also feasible. This review gives a brief overview of the development of this radiation-free imaging modality, explains the measuring principle of EIT and the basics of EIT image generation and presents the results of validation studies related to pulmonary applications of EIT. Recent experimental and clinical studies with postulated relevance for the future clinical use of EIT are discussed. Finally, the perspectives and limitations of this method are outlined. Introduction Electrical impedance tomography (EIT) is a relatively new non-invasive, radiation-free medical imaging technique. Over the last few years, intensivists have become increasingly interested in this method. This is mainly related to the fact that EIT offers the possibility of bedside monitoring of regional lung aeration and ventilation. Potentially, regional lung perfusion might also be monitored by EIT. Recent editorials, published in leading critical care journals [1, 2], provide good evidence of this rising clinical interest. This review briefly presents the basic characteristics of the EIT technique, summarizes the main results of lung-oriented EIT studies performed so far and gives an overview of possible clinically relevant applications in intensive care patients.

Historical overview EIT was invented more than 20 years ago. In 1984, the first EIT tomogram (a cross-sectional image of the human forearm) was generated [3]. Only one year later in 1985, the first EIT scan of the human chest, clearly showing both lungs, followed [4]. Over the two decades, immense development of this method took place. About twenty research groups, most of them located in Europe, significantly improved the EIT hardware and software, identified the major fields of possible future application and conducted multiple methodological validation studies, as well as experimental animal and clinical studies. The European lead in EIT has largely been promoted by the meetings programme of the European Concerted Action on Electrical Impedance Tomography. Since the mid 1990s the development of multifrequency EIT systems has also been pursued. The application of EIT in pulmonary conditions has always been thought promising, although other applications (e.g. detection or monitoring of breast cancer, pharyngeal and gastric motility, cortical brain activity, pulmonary and peripheral blood perfusion, cardiac performance, urinary bladder emptying, uterus activity) have also been considered [5-7]. In 2000, a review of all EIT research activities related to lung and

Correspondence: I Frerichs E-mail: [email protected]

Figure 1. Basic principle of electrical impedance tomography (EIT). Rotating electrical current (I) injection is performed between pairs of adjacent surface electrodes (denoted by numbers 1-16), and resulting voltages (U) are measured between pairs of remaining electrode pairs. Reprinted from [18] with permission from The American Physiological Society.

ventilation, summarized the major results that had been achieved and outlined the perspectives and limitations of EIT in this field [8]. From the results of various lung-oriented EIT studies available at that time, it was concluded that mechanically ventilated intensive care patients would benefit the most from the use of EIT. Several experimental and clinical studies, performed over the recent years [9-13], seem to confirm this conclusion.

Measuring principle of EIT Biological tissues conduct electrical current because they contain ions which act as charge carriers. The number of ions in a defined volume differs within human tissues which is the reason why there are large differences in the conductivity (or resistivity) of different tissues [14]. For instance, blood and muscle are good conductors, whereas bone and fat are poor conductors. The idea of imaging the human body using electricity is based on the existence of the dissimilar electrical properties of tissues and organs. EIT makes use of this fact and generates cross-sectional images (i.e. scans) of internal distribution of electrical impedance (i.e. resistance to alternating electrical current) within a chosen part of the human body. To determine the electrical properties of the tissues



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Figure 2. Generation of a functional EIT scan of regional lung ventilation (right) from a series of EIT scans (left) acquired during tidal breathing. The individual scans in the series show the instantaneous local changes in electrical impedance within the chest cross-section with respect to the average local electrical impedance determined from all tidal respiratory cycles measured. Expiration decreases the local air content and leads to a fall in regional electrical impedance, inspiration is accompanied by an increase in regional electrical impedance. The fall in local electrical impedance is shown in dark tones and the lungs appear black during expiration shown in the first EIT scan of the series. The rise in local electrical impedance is depicted in light tones and the lungs appear white during inspiration shown in the last scan of the series. The local time courses of relative impedance change (rel. ΔZ) in two out of a total of 912 pixels show tidal fluctuations in local electrical impedance synchronous with the breathing rate (centre). The differences between the end-inspiratory and end-expiratory relative impedance changes (vertical arrows to the right of both diagrams) are proportional to the local tidal changes in air content. The calculated local end-inspiratory-to-end-expiratory relative impedance changes are plotted in the corresponding pixel locations using a black-and-white scale. In this way, one functional EIT scan of regional lung ventilation is generated from a series of hundreds of primary EIT scans. Reprinted from [43] with permission from Elsevier.

contained in the body segment under study, very small alternating currents are repeatedly applied through a set of electrodes placed on the surface of the body and the resulting potential differences are measured. The measuring principle of EIT is depicted in Figure 1 showing schematically an EIT measurement of the chest. The boundary voltage data acquired during the cyclic and rotating application of electrical currents are then processed to generate the EIT images. This process is called image reconstruction.

Generation of EIT images In general, there are three ways of EIT imaging [15]: 1) imaging the distribution of impedance within the body, 2) imaging the frequency variation of impedance within the body, and 3) imaging the variation in impedance during a physiological process e.g. breathing or cardiac activity. The first two approaches are essentially anatomical because they show how different tissues are distributed within the section under study. The resulting EIT scans reflect the momentary distribution of regional electrical tissue properties. The first two approaches are inferior to established imaging techniques like computed tomography (CT) or magnetic resonance tomography (MRT) because of the lower spatial resolution of EIT scans. The philosophy of the third approach is different as it is oriented to imaging the function and not merely anatomy. In this respect EIT is superior to established methods as it enables detection of changes in organ function.

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Figure 3. Correlation between the changes in lung air content determined by electronic beam computed tomography (EBCT) and electrical impedance tomography (EIT) at the dorsal (top), middle (middle) and ventral lung regions (bottom) of the right and left lungs. The data were obtained in six pigs ventilated in a volume-controlled mode with five different tidal volumes at three PEEP levels. R, correlation coefficient. Reprinted from [22] with permission from The American Physiological Society.


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Figure 4. EIT measurement performed during volume-controlled ventilation with different tidal volumes (VT) at a constant positive end-expiratory pressure (PEEP) of 5 cmH2O (left) and a constant VT of 500 ml at varying PEEP levels (right). The breath-by-breath amplitudes of the EIT signal clearly reflect the stepwise changes in VT (top left). The shifts in the end-expiratory values of the EIT signal are representative of the lung volume changes associated with the stepwise variation of PEEP (top right). Reprinted from [19] with permission (©1999 IEEE).

Moreover, it is suitable for long-term monitoring of such functional changes because of its radiation-free measuring principle. The first functional EIT images were published in the mid-1990s [16, 17]. The generation of functional EIT scans is based on the acquisition of time series of EIT scans with subsequent off-line or online evaluation. In the case of lung imaging, the most promising approach is to quantify the ventilation-related changes in regional impedance. This approach, based on the determination of impedance changes occurring between inspiration and expiration, is shown in Figure 2. Other types of functional EIT data evaluation are also feasible. For instance, if a change in regional lung aeration takes place during the EIT scanning period, the corresponding shift in local air content is accompanied by a shift in local impedance which can be quantified and a functional EIT scan showing this change in local lung air volume generated. Functional scans of this type have previously been generated both during spontaneous breathing manoeuvres and mechanical ventilation [18, 19]. They can be applied to study the changes in local aeration over a period of time. Similarly, changes in fluid content may induce impedance changes which can also be visualized. Another type of functional EIT scan has been developed to characterize the regional dynamic behaviour of lungs [18] based on the following consideration: the differences in regional lung mechanics result in different patterns of regional lung filling and emptying during ventilation which is accompanied by regionally dissimilar changes in impedance over time. Thanks to the good time resolution of EIT scanning, the local changes in impedance can be sampled at a high rate and the local filling or emptying characteristics of the lung tissue mathematically described (e.g. by fitting a polynomial function

to the EIT data). These scans and the quantitative variables derived from such evaluation may provide valuable information, e.g. on lung overdistension. In summary, functional EIT in ventilation-oriented applications is capable of assessing different aspects of regional lung function, e.g. regional tidal volume distribution, shifts in regional lung aeration or regional filling and emptying behaviour. The positive side effect of functional EIT data evaluation is the elimination of the problem of interpreting a time series of hundreds or thousands of simple EIT images. We expect that new functional evaluation tools will be applied in the future to extract further information from EIT measurements and enhance the clinical relevance of the findings.

EIT studies related to lung ventilation and perfusion The validity of EIT with respect to its ability to correctly measure regional changes in lung air content is the crucial prerequisite for the clinical application of this technique as a monitoring tool of regional lung ventilation. The early validation studies used simple spirometry to establish the relationship between the global changes in lung volume and the EIT signal [16, 20, 21]. Later, more efficient reference techniques like CT [10], electron beam CT [22], single photon emission CT [23], ventilation scintigraphy [24] and nitrogen washout [12] were applied. Good correlation between the regional air content changes determined by EIT and the respective reference technique was found ( Figure 3). In mechanically ventilated patients, changes in ventilator settings influence the regional distribution of ventilation and aeration and several EIT studies have demonstrated that these changes are discernible by EIT. Figure 4 shows the instantaneous changes in the



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Figure 5. Tracings of local relative impedance change (right top, dark thick lines) during volume controlled ventilation at different PEEP levels in four regions of interest in the right lung (left top) before and after surfactant treatment. An increase in local aeration is accompanied by an increase in electrical impedance, the small fluctuations of the impedance signal represent the individual breaths. For better comparison and identification of instantaneous changes of end-expiratory lung volume and tidal volume with PEEP, the individual tracings were normalized and plotted together with the tracing of average relative impedance change in the whole thoracic cross-section (light thin lines). Timing of the PEEP manoeuvre (left bottom) and the tracings of airway pressure (right bottom) are shown. Z impedance; Pao pressure at the airway opening. Reprinted from [29] with permission from Springer.

EIT signal reflecting the changes in two basic ventilator parameters: tidal volume (VT) and positive end-expiratory pressure (PEEP). The data presented in the figure originate from an animal experimental study. The effects of various types of mechanical ventilation (e.g. intermittent and continuous positive pressure ventilation, synchronized intermittent mandatory ventilation, spontaneous breathing with continuous positive airway pressure, high frequency oscillatory ventilation) on regional lung ventilation have been established by EIT

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both in adult and neonatal intensive care patients [10, 11, 25-27]. EIT has also been shown to detect the changes in regional lung ventilation, aeration and lung mechanics associated with acute lung injury or lung oedema both in experimental [9, 28-31] and clinical settings [32]. Regional pressure-volume curves were generated by EIT in surfactant depleted animals [29, 33, 34] and patients [35] clearly demonstrating the topographic heterogeneity of the relationship between the imposed airway pressure and regional lung vol-


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Figure 6. Local time-impedance (six left-hand diagrams) and time-density curves (six right-hand diagrams) in a pig during the administration of a bolus of hypertonic saline solution and radiographic contrast material, respectively. The black crosses in the dorsal regions of the right and left lungs in the functional EIT images of lung ventilation and in the electronic beam computed tomography images (top) indicate the pixel locations at which the data were obtained. Three drawings of the lungs show schematically the position of the Swan-Ganz catheter in a branch of the left pulmonary artery and the bolus administration sites (black arrows). The bolus was administered either through the distal (upper drawing) or the proximal opening of the catheter with the balloon at the tip of the catheter being inflated (middle drawing) or deflated (lower drawing). Reprinted from [38] with permission (©2002 IEEE).

umes. Figure 5 shows the results of an EIT measurement performed in an experimental animal with acute lung injury induced by repeated bronchoalveolar lavage. Large dissimilarities in regional lung filling and emptying existed during the slow inflation and deflation manoeuvres. This figure also shows the beneficial effect of surfactant administration on regional lung mechanics detected by EIT. An improvement of regional lung ventilation distribution in response to surfactant treatment has also been documented by EIT examinations in preterm infants suffering from the infant respiratory distress syndrome [11]. The generation of regional pressure-volume curves by EIT enabling the identification of regional inflection points both during interrupted conventional mechanical [35, 36] and high-frequency oscillatory ventilation [9] opens the possibility of quasi-online PEEP titration at the bedside. There are a few studies which indicate that EIT might be suitable not only for assessing regional lung ventilation but also for lung perfusion [37-40]. Changes in regional electrical impedance associated with cardiac activity and pulmonary perfusion are much lower than those elicited by ventilation. However, filtering procedures or ECG-

gated EIT data acquisition make the impedance changes occurring synchronously with the heart rate accessible for analysis and interpretation. The size of the microvascular bed has been found to significantly influence the EIT signal whereas the cardiac stroke volume and pulmonary artery distensibility did not have this effect [40, 41]. Consequently, these studies show the potential of EIT for measuring the pulmonary vascular reactivity. EIT results obtained after pharmacologically induced pulmonary vasodilation [39] also indicate this possibility. Promising results have also been achieved by the use of an EIT contrast agent (hypertonic saline solution) applied as an intravenous bolus for generation of regional pulmonary dilution curves and calculation of regional pulmonary blood flow [38] (Figure 6).

Need for a new lung imaging modality EIT is able to detect highly interesting physiological and pathological phenomena in regional lung function. It is difficult to asses if this justifies the introduction of this technique into a clinical setting already at the present state of development. Nevertheless, several nega-



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tive features of existing medical techniques indicate the need for a new diagnostic and monitoring modality. At present there are several well established medical techniques which, along with the personal experience of the physicians, are applied as guidance for ventilator therapy. To assess the overall efficacy of pulmonary gas exchange, arterial, capillary and venous blood gas analysis, pulse oximetry, transcutaneous O2 and CO2 measurement, as well as end-tidal CO2 measurement are used. However, these methods provide only global information on lung function and may mask regional differences in gas exchange. Morphological information on the lung structure may be obtained from chest X-ray, CT or MRT examinations. However, the use of these techniques is limited by several factors. Chest radiography and CT increase the radiation exposure which is extremely unfavourable especially in critically ill neonates. Although simple chest X-ray examinations can be performed at the bedside, the use of other imaging techniques requires the transport of patients. Transport from the ICU is associated with an increased risk because of the interruption and/or disturbance of therapy. The established imaging modalities are not suitable for monitoring regional lung function as they primarily provide only a momentary anatomical image of lungs, albeit with excellent spatial resolution. Thus, there is still a need for a new monitoring technique which is able to 1) determine regional lung aeration and ventilation directly at the bedside and 2) provide immediate feedback information on regional response of the lung tissue to changes in, primarily ventilator, therapy. There is rising clinical awareness of this deficit in lung function monitoring due to the increasing amount of knowledge of the heterogeneity of regional lung function. Even under physiological conditions, regional lung volumes, ventilation, perfusion and gas exchange are not homogeneously distributed within the lungs. All lung diseases further increase this pulmonary functional heterogeneity mainly due to regionally dissimilar changes in lung mechanics. It is well-known that, an acute lung injury for example, produces a marked heterogeneity of mechanical properties of lung tissue which make different lung regions susceptible to traumatic events elicited by mechanical ventilation. Overextended, atelectatic, cyclically opening and collapsing regions as well as normally ventilated regions can exist in the lungs at the same time. Established techniques providing global information on lung function (blood gas analysis, spirometry, generation of pressure-volume curves) do not allow conclusions to be drawn on regional behaviour of the lung tissue and, consequently, optimum ventilator settings.

Perspectives and limitations of EIT use in intensive care patients EIT has the potential for becoming a new monitoring technique in the ICU primarily as a tool for optimizing ventilator therapy. EIT is able to assess changes in regional ventilation, aeration, perfusion and lung mechanics. Several experimental and clinical studies have provided proof of this ability to determine several aspects of lung function on a regional level. EIT has no known hazards, it is fully non-invasive and uses a radiation-free measuring principle. The technology is relatively cheap, the devices are small and further miniaturization is to be expected.

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Thus, EIT can easily be applied at the bedside. EIT examinations can be performed with an excellent time resolution (at present, scan rates up to about 40 scans per second are possible). In spite of all these positive features and advantages the method has also certain limitations which may limit its future clinical use. 1) the spatial resolution of EIT scans is low when compared with radiographic imaging techniques. For instance, the EIT scans shown in this review have a resolution of only 32 x 32 pixels. The resolution of EIT images cannot be significantly improved even if higher numbers of electrodes are used [42]. Therefore, EIT can only be recommended for functional and not purely anatomical imaging. 2) the method requires the use of self-adhesive electrodes which have to be placed on the chest circumference. Patients have to be turned to both sides to allow the application of electrodes. The cables connecting the electrodes to the EIT device make nursing care more difficult. 3) EIT is still an experimental method and the existing EIT data evaluation tools have been developed for specific research projects and are not universally applicable. Therefore, complex and innovative evaluation of EIT data is only accessible to experts. 4) changes in regional lung impedance may result from different physiological and pathophysiological processes. For instance, both an increase in regional fluid content and a decrease in air content result in a fall of local lung impedance. Only the measurement of absolute values of electrical impedance and/or measurement using electrical currents of multiple frequencies may allow a differentiation of such processes. 5) EIT use in an electrically noisy environment like ICU is challenging. Although modern EIT devices are rather robust and EIT measurements in a clinical setting are usually not problematic, the possible disturbances of the measurements caused by other electrical devices leading to decreased quality of EIT data should not be neglected. Nevertheless, many of the limitations of the existing EIT technology can be eliminated in the future. For instance, new electrode belts and software for data evaluation may be developed. Further development of EIT hardware may improve the quality of EIT measurements and even make the determination of absolute impedance and multifrequency measurements possible and reliable. Potential benefits and advantages of EIT prevail and make the further development of this technique worthwhile and its future use in ICU possible.

Conclusion EIT is a new, portable imaging technique which is increasingly being considered as a future tool for evaluation of immediate effects of a change in ventilation or other therapeutic intervention in critically ill patients. The method is suitable for monitoring regional lung function directly at the bedside. The steady advance in the development of EIT technology over the past 20 years indicates that routine application in a clinical setting in the next decade will be possible. Nevertheless, further development of both EIT hardware and software is necessary to increase the quality of data, user-friendliness and clinical acceptance. Proof of clinical efficiency has to be provided. Results of several studies indicate that EIT might be of benefit in optimizing ventilator therapy and minimizing the incidence of ventilator-associated lung injury but this has to be proved in larger clinical trials.


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References 1. Arnold JH. 2004. Electrical impedance tomography: on the path to the Holy Grail. Crit Care Med. 32:894-5. 2. Hedenstierna G. 2004. Using electric impedance tomography to assess regional ventilation at the bedside. Am J Respir Crit Care Med. 169:777-8. 3. Barber D, Brown B. 1984. Applied potential tomography. J Phys E:Sci Instrum. 17:723-33. 4. Brown BH, Barber DC, Seagar AD. 1985. Applied potential tomography: possible clinical applications. Clin Phys Physiol Meas. 6:109-21. 5. Kotre CJ. 1997. Electrical impedance tomography. Br J Radiol. 70 Spec No:S200-5. 6. Holder DS, Brown BH. 1994. Biomedical applications of EIT: a critical review. In: Holder DS (ed). Clinical and Physiological Applications of Electrical Impedance Tomography. London, UCL press. pp 6-40 7. Avill R, Mangnall YF, Bird NC, Brown BH, Barber DC, Seagar AD, Johnson AG, Read NW. 1987. Applied potential tomography. A new noninvasive technique for measuring gastric emptying. Gastroenterology. 92:1019-26. 8. Frerichs I. 2000. Electrical impedance tomography (EIT) in applications related to lung and ventilation: a review of experimental and clinical activities. Physiol Meas. 21:R1-21. 9. van Genderingen HR, van Vught AJ, Jansen JR. 2004. Regional lung volume during high-frequency oscillatory ventilation by electrical impedance tomography. Crit Care Med. 32:787-94. 10. Victorino JA, Borges JB, Okamoto VN, Matos GF, Tucci MR, Caramez MP, Tanaka H, Sipmann FS, Santos DC, Barbas CS, Carvalho CR, Amato MB. 2004. Imbalances in regional lung ventilation: a validation study on electrical impedance tomography. Am J Respir Crit Care Med. 169:791-800. 11. Frerichs I, Schiffmann H, Hahn G, Hellige G. 2001. Noninvasive radiation-free monitoring of regional lung ventilation in critically ill infants. Intensive Care Med. 27:1385-94. 12. Hinz J, Hahn G, Neumann P, Sydow M, Mohrenweiser P, Hellige G, Burchardi H. 2003. End-expiratory lung impedance change enables bedside monitoring of endexpiratory lung volume change. Intensive Care Med. 29:37-43. 13. Odenstedt H, Lindgren S, Olegard C, Erlandsson K, Lethvall S, Aneman A, Stenqvist O, Lundin S. 2005. Slow moderate pressure recruitment maneuver minimizes negative circulatory and lung mechanic side effects: evaluation of recruitment maneuvers using electric impedance tomography. Intensive Care Med. 31:170614. 14. Geddes LA, Baker LE. 1967. The specific resistance of biological material-a compendium of data for the biomedical engineer and physiologist. Med Biol Eng. 5:271-93. 15. Boone K, Barber D, Brown B. 1997. Imaging with electricity: report of the European Concerted Action on Impedance Tomography. J Med Eng Technol. 21:201-32. 16. Hahn G, Sipinkova I, Baisch F, Hellige G. 1995. Changes in the thoracic impedance distribution under different ventilatory conditions. Physiol Meas. 16:A161-73. 17. Leathard AD, Brown BH, Campbell J, Zhang F, Morice AH, Tayler D. 1994. A comparison of ventilatory and car-

diac related changes in EIT images of normal human lungs and of lungs with pulmonary emboli. Physiol Meas. 15 Suppl 2a:A137-46. 18. Frerichs I, Dudykevych T, Hinz J, Bodenstein M, Hahn G, Hellige G. 2001. Gravity effects on regional lung ventilation determined by functional EIT during parabolic flights. J Appl Physiol. 91:39-50. 19. Frerichs I, Hahn G, Hellige G. 1999. Thoracic electrical impedance tomographic measurements during volume controlled ventilation-effects of tidal volume and positive end-expiratory pressure. IEEE Trans Med Imaging. 18:764-73. 20. Harris ND, Suggett AJ, Barber DC, Brown BH. 1987. Applications of applied potential tomography (APT) in respiratory medicine. Clin Phys Physiol Meas. 8 Suppl A:155-65. 21. Harris ND, Suggett AJ, Barber DC, Brown BH. 1988. Applied potential tomography: a new technique for monitoring pulmonary function. Clin Phys Physiol Meas. 9 Suppl A:79-85. 22. Frerichs I, Hinz J, Herrmann P, Weisser G, Hahn G, Dudykevych T, Quintel M, Hellige G. 2002. Detection of local lung air content by electrical impedance tomography compared with electron beam CT. J Appl Physiol. 93:660-6. 23. Hinz J, Neumann P, Dudykevych T, Andersson LG, Wrigge H, Burchardi H, Hedenstierna G. 2003. Regional ventilation by electrical impedance tomography: a comparison with ventilation scintigraphy in pigs. Chest. 124:314-22. 24. Kunst PW, Vonk Noordegraaf A, Hoekstra OS, Postmus PE, de Vries PM. 1998. Ventilation and perfusion imaging by electrical impedance tomography: a comparison with radionuclide scanning. Physiol Meas. 19:481-90. 25. Frerichs I, Hahn G, Golisch W, Kurpitz M, Burchardi H, Hellige G. 1998. Monitoring perioperative changes in distribution of pulmonary ventilation by functional electrical impedance tomography. Acta Anaesthesiol Scand. 42:721-6. 26. Kunst PW, de Vries PM, Postmus PE, Bakker J. 1999. Evaluation of electrical impedance tomography in the measurement of PEEP-induced changes in lung volume. Chest. 115:1102-6. 27. Wolf GK, Arnold JH. 2005. Noninvasive assessment of lung volume: respiratory inductance plethysmography and electrical impedance tomography. Crit Care Med. 33:S163-9. 28. Brown BH, Flewelling R, Griffiths H, Harris ND, Leathard AD, Lu L, Morice AH, Neufeld GR, Nopp P, Wang W. 1996. EITS changes following oleic acid induced lung water. Physiol Meas. 17 Suppl 4A:A117-30. 29. Frerichs I, Dargaville PA, Dudykevych T, Rimensberger PC. 2003. Electrical impedance tomography: a method for monitoring regional lung aeration and tidal volume distribution? Intensive Care Med. 29:2312-6. 30. Frerichs I, Hahn G, Schroder T, Hellige G. 1998. Electrical impedance tomography in monitoring experimental lung injury. Intensive Care Med. 24:829-36. 31. Newell JC, Edic PM, Ren X, Larson-Wiseman JL, Danyleiko MD. 1996. Assessment of acute pulmonary edema in dogs by electrical impedance imaging. IEEE Trans Biomed Eng. 43:133-8.

32. Kunst PW, Vonk Noordegraaf A, Raaijmakers E, Bakker J, Groeneveld AB, Postmus PE, de Vries PM. 1999. Electrical impedance tomography in the assessment of extravascular lung water in noncardiogenic acute respiratory failure. Chest. 116:1695-702. 33. Kunst PW, Bohm SH, Vazquez de Anda G, Amato MB, Lachmann B, Postmus PE, de Vries PM. 2000. Regional pressure volume curves by electrical impedance tomography in a model of acute lung injury. Crit Care Med. 28:178-83. 34. van Genderingen HR, van Vught AJ, Jansen JR. 2003. Estimation of regional lung volume changes by electrical impedance pressures tomography during a pressure-volume maneuver. Intensive Care Med. 29:233-40. 35. Hinz J, Moerer O, Neumann P, Dudykevych T, Frerichs I, Hellige G, Quintel M. 2006. Regional pulmonary pressure volume curves in mechanically ventilated patients with acute respiratory failure measured by electrical impedance tomography. Acta Anaesthesiol Scand. 50:331-9. 36. Kunst PW, Vazquez de Anda G, Bohm SH, Faes TJ, Lachmann B, Postmus PE, de Vries PM. 2000. Monitoring of recruitment and derecruitment by electrical impedance tomography in a model of acute lung injury. Crit Care Med. 28:3891-5. 37. Brown BH, Leathard A, Sinton A, McArdle FJ, Smith RW, Barber DC. 1992. Blood flow imaging using electrical impedance tomography. Clin Phys Physiol Meas. 13 Suppl A:175-9. 38. Frerichs I, Hinz J, Herrmann P, Weisser G, Hahn G, Quintel M, Hellige G. 2002. Regional lung perfusion as determined by electrical impedance tomography in comparison with electron beam CT imaging. IEEE Trans Med Imaging. 21:646-52. 39. Smit HJ, Vonk Noordegraaf A, Roeleveld RJ, Bronzwaer JG, Postmus PE, de Vries PM, Boonstra A. 2002. Epoprostenol-induced pulmonary vasodilatation in patients with pulmonary hypertension measured by electrical impedance tomography. Physiol Meas. 23:237-43. 40. Vonk Noordegraaf A, Kunst PW, Janse A, Marcus JT, Postmus PE, Faes TJ, de Vries PM. 1998. Pulmonary perfusion measured by means of electrical impedance tomography. Physiol Meas. 19:263-73. 41. Smit HJ, Vonk Noordegraaf A, Marcus JT, Boonstra A, de Vries PM, Postmus PE. 2004. Determinants of pulmonary perfusion measured by electrical impedance tomography. Eur J Appl Physiol. 92:45-9. 42. Seagar AD, Barber DC, Brown BH. 1987. Theoretical limits to sensitivity and resolution in impedance imaging. Clin Phys Physiol Meas. 8 Suppl A:13-31. 43. Frerichs I, Braun P, Dudykevych T, Hahn G, Genee D, Hellige G. 2004. Distribution of ventilation in young and elderly adults determined by electrical impedance tomography. Respir Physiol Neurobiol. 143:63-75.



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What are the consequences of PEEPi during spontaneous and controlled ventilation in patients with chronic obstructive lung disease L.M. Dijkema, J.E. Tulleken, J.J.M. Ligtenberg, J.H.J. Meertens, J.S.W. Lind, J.G. Zijlstra Intensive & Respiratory Care Unit (ICB), University Medical Center Groningen

Introduction. PEEPi, intrinsic PEEP, dynamic hyperinflation, occult PEEP and auto-PEEP are various terms used to describe the presence of a positive end-expiratory alveolar pressure greater than the applied extrinsic PEEP, due to incomplete expiration. The possible consequences of intrinsic positive end-expiratory pressure (PEEPi) were first described by Pepe and Marini in 1982 [1]. In this article we will focus on the effects of PEEPi in the context of severe airway obstruction, because in this situation PEEPi is most pronounced and its consequences the most serious. The principles described, however, apply to all situations in which PEEPi occurs.

What is PEEPi ? In the normal physiological situation expiration is a passive process. The elastic energy stored in the respiratory system during the preceding inspiration is sufficient to deflate the lungs until the expiratory flow ceases. The amount of air that remains in the lungs and airways at the end of expiration is the functional residual capacity (FRC). FRC is determined by the opposing elastic forces of the lungs and the chest wall. If expiration time is too short, the next inspiration will start before expiration is complete and the lung volume will increase to a level greater than FRC. There will thus be raised residual endexpiratory alveolar pressure: PEEPi. If this phenomenon is repeated there will be a progressive increase in FRC exceeding the elastic equilibrium volume of the total respiratory system (dynamic hyperinflation) (Figure 1) [2]. Patients with COPD and asthma are at high risk of developing PEEPi, as will be discussed below. Diminished expiration can also be seen in other patients such as after foreign body aspiration or endobronchial located clots following thoracic trauma. The foreign body or clot acts like a ball-valve, causing hyperinflation in the affected part of the lungs with each breath. In COPD patients PEEPi is a consequence of the limited elastic recoil of their lungs causing prolonged expiratory time and the presence of expiratory flow obstruction. The chance, therefore, that the next inspiration starts before the end of expiration is high. Furthermore, they have highly compliant lungs; the air flows easily into the lungs and the inspiratory volume is large. The time needed to fully expire this large inspiratory volume may be as long as 20 seconds. Bronchospasm, inflammation, air-trapping and increased secretions are patient-related factors that can lead to expiratory flow obstruction. Physicians can further add to this expiratory flow resistance with an endotracheal tube, the ventilator tubing and kinking of the tubes. Another factor that influences the development of PEEPi is the ventilatory pattern [2-4]: ventilatory frequency and I/E ratio directly determine expiratory time. High tidal volumes also increase the risk of PEEPi due to the larger volume to be expired. The highest PEEPi Correspondence: JE Tulleken E-mail: [email protected]

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is, therefore, measured in patients with obstructive airway disease (asthma, COPD) and may worsen with assisted and mechanical ventilation. There are, as in ARDS, also possible benefits of PEEPi. In this situation PEEPi is mostly induced by the lower tidal volume ventilatory strategy aiming to improve oxygenation and prevent lung injury [5]. The hazards of PEEPi are its variability (a small change in airway resistance can lead to a rapid increase in the level of PEEPi) and the fact that it often goes undetected (in mechanically ventilated patients this pressure is not transmitted to the ventilator pressure sensors at the airway opening). PEEPi raises both alveolar pressure and intrathoracic pressures. High intrathoracic pressure impedes venous return to the heart, thereby reducing cardiac output [6]. This phenomenon has been likened to applying a tourniquet to the right cardiac system [7]. These effects are exaggerated in patients with COPD because highly compliant lungs enhance transmission of alveolar pressure to intrathoracic vessels. Another negative haemodynamic effect is an increased afterload of the right ventricle due to the high pulmonary capillary resistance secondary to the high alveolar volume.

Measurement of PEEPi. The presence of PEEPi can be identified by inspection of the expiratory flow-time curve. When expiratory time is sufficient for full expiration, expiratory flow declines from a maximum to zero. The presence of expiratory flow at the end of expiration indicates that the end-expiratory alveolar pressure is higher than the atmospheric pressure or the applied PEEP. If expiration is interrupted there will be an abrupt change in the slope of the curve, immediately followed by the next inspiratory flow (figure 2). A ventilator cannot generate flow into the patient’s lungs until the pressure at the airway opening exceeds the end-expiratory pressure. One way to measure the level of PEEPi is, therefore, to determine the airway pressure at the precise time of inspiratory flow commencement. This is called the dynamic PEEPi. As time constants of different lung units are unequal, PEEPi is not distributed homogeneously within the lungs: there are lung units with long time constants and slow expiration and lung units with short time constants and rapid expiration. Consequently when inspiratory flow commences, only


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6000

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Figure 1. The first part of this figure shows the different lung volumes. The second part (dotted line) shows the mechanism of dynamic hyperinflation in the presence of expiratory flow obstruction. There is a progressive increase in FRC. If the process of dynamic hyperinflation continues the inspiratory capacity declines because the lungs are “full”.

the units with short time constants start filling, while the units with long time constants are still emptying. Measurement of dynamic PEEPi will thus reflect the lowest regional PEEPi and underestimate the actual level of PEEPi [8]. PEEPi can also be measured by end-expiratory occlusion of the expiratory port of the ventilator. The airway pressure can then equiliPEEPi brate with mean alveolar pressure. In the case of heterogenous lungs it takes a number of seconds to reach the plateau pressure, making this method only possible in the absence of spontaneous breathing. The level of PEEPi obtained by this technique is the static PEEPi. Measurement of PEEPi during assisted spontaneous ventilation is much more difficult than during controlled ventilation as respiratory 15 muscles are active. The only reliable and readily available method in this scenario is to use an oesophageal balloon catheter to measure the drop in oesophageal pressure that occurs before the flow becomes inspiratory [9, 10]. In practice, identification of PEEPi is more important than its exact quantification. In mechanically ventilated patients continuous display of the flow-volume curve on the ventilator is therefore recommended. Auscultation of the chest or the tube during expiration is also helpful in detecting PEEPi: if the expiratory sound does not cease, there is still expiratory flow. One has to bear in mind that in the case of extreme airway obstruction the flow can be too small to be detected either by auscultation or the displayed flow measurement. Hyperresonant percussion, decreased tidal volume with higher plateau pressure, abdominal distension, hypotension and pulsus paradoxus are additional signs of the presence of PEEPi. The most important difAlveolus ferential diagnosis to be excluded is a tension pneumothorax [11].

Consequences of PEEPi Once the physiology of PEEPi is understood, it is easier to work out what the consequences are. PEEPi can have ventilatory as well as circulatory consequences.

Ventilatory consequences

In the presence of PEEPi the lungs and chest wall are overstretched. This leads to an increased breathing workload, because the lungs and respiratory muscles function on a non-optimal part of their pressure-volume and length-tension curve. In the presence of airflow obstruction the work of breathing is further increased by the use of PEEPe expiratory muscles as expiration becomes active instead of passive. In assisted mechanical ventilation the presence of PEEPi impairs triggering of the ventilator because the level of PEEPi has to be overcome before the triggering threshold is reached. All these factors may contribute to difficulty in weaning from the ventilator [8,12]. In pressure controlled mechanical ventilation there will be a low12 8 0 er tidal volume with the same peak pressure due to lower compliance of the lungs. High levels of PEEPi will thus lead to impaired ventilation. In volume controlled ventilation the peak and plateau pressures will steadily increase leading to dynamic hyperinflation with increased risk of barotrauma. In the presence of extremely high levels of PEEPi it can become almost impossible to further inflate the lungs, because they are “full”. This leads to markedly impaired ventilation. Circulatory consequences

The high intrathoracic pressure in the presence of PEEPi can lead to reduced diastolic filling, decreased venous return, decreased cardiac output and hypotension. In extreme cases this can even cause electrical mechanical dissociation (EMD) [11, 13]. EMD can also develop during CPR in a patient with obstructive pulmonary disease as vigorous positive pressure ventilation, allowing insufficient expiration Ventilator time, is frequently administered in this situation. Misinterpretation of the elevated central venous pressure, endexpiratory pulmonary artery wedge pressure, reduced cardiac output and blood pressure may lead to inappropriate fluid restriction or unnecessary vasopressor therapy.

20 n eth j crit care • volume 10 • no 4 • august 2006


Alveolar Pressure (cmH20)

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20

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Figure 2. Pressure and flow curves demonstrating the generation if intrinsic PEEP(PEEPi). The first part of the figure portrays the normal situation in which the expiratory flow returns to zero before the next inspiration starts. The second part of the figure shows what happens in the presence of expiratory flow obstruction: there is still expiratory flow at the start of the next inspiration causing a subsequent rise in end-expiratory alveolar pressure (PEEPi).

Treatment of PEEPi. Prevention and reduction of PEEPi has a major impact on patients with obstructive airways disease like COPD and asthma, as it frequently occurs in these patients and may reach excessive values [14]. The ventilation strategy used is very important. However, recommendations for the optimal ventilator setting are difficult to be made. Is volume controlled ventilation the answer to PEEPi in severe COPD in ICU patients? Many intensivists believe so, as do we, but conclusive research still is lacking. We feel that, first, in volume controlled ventilation the ventilator should be set so as to provide the longest expiratory time compatible with patient comfort and gas exchange. This can be achieved with low frequency (e.g. 8-10 breaths/min) and short but sufficient inspiratory time with high inspiratory flow(e.g. Tinsp 1.0 second, flow 70-100 l/min). The latter will lead to high peak pressures, due to the high intrinsic resistance of the ventilator tubing and the conductive airways, but will not affect alveolar pressure. It is important to adjust the ventilator peak pressure (to e.g. 80 cmH2O) and to aim for a plateau pressure under 30 cmH2O by adjusting the programmed tidal volume. The large difference between peak pressure and plateau pressure is the reason why pressure controlled ventilation is not recommended in the presence of severe airflow obstruction. Second, although often applied, the use of extrinsic PEEP in volume controlled ventilation in chronic obstructive lung disease remains controversial. Theoretically, extrinsic PEEP possibly prevents air-trapping by splinting the airways open(figure 3). However, if the applied extrinsic PEEP is larger than the PEEPi airway trapping will worsen. Due to the difficulty in measuring the exact level of PEEPi it is recommended to minimize the use of extrinsic PEEP and to never exceed levels greater than 80% of PEEPi [17]. Furthermore, it is important to assess the effect of the applied extrinsic PEEP by continuous careful observation [18]. Addition of extrinsic PEEP is advocated in assisted ventilation so as to reduce the work of breathing by attenuating the inspiratory muscle effort needed to trigger the ventilator. The patient must otherwise overcome the PEEPi completely before the ventilator senses a spontaneous breathing attempt.

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PEEPi

PEEPe

15

0

12

8

Alveolus

Ventilator

Figure 3. This figure demonstrates how the use of extrinsic PEEP(PEEPe) may be useful in the presence of air trapping to prevent airway collapse by splinting the airways open. PEEPe minimizes the difference between alveolar and upstream pressures. The level of intrinsic PEEP(PEEPi) will decrease because a greater volume is expired.

The measures above may not be sufficient. The time needed for full expiration in severe airway obstruction can be as long as 20 seconds. Another strategy to limit PEEPi is controlled hypoventilation with decreased tidal volumes so that the amount of gas to be exhaled is reduced. This will result in carbon dioxide retention but this “permissive hypercapnia”, which maintains a pH above 7.20 or a pCO2 below 12 kPa, has gained widespread acceptance. Adequate sedation and analgesia are essential in lowering carbon dioxide production and subsequently ventilatory requirements. The use of neuromuscular blocking agents should be limited to short periods and only when absolutely necessary because of the evidence of the risk of developing myopathy, especially when combined with steroids.


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Treatment of airway obstruction with bronchodilators is recommended 15], as is the use of steroids to reduce inflammation and the amount of secretions [16]. Other treatment recommendations are avoidance of rapid ventilation during CPR, especially in patients with known obstructive airway disease, and the use of a trial of ventilator disconnection during CPR for EMD.

Conclusion PEEPi is frequently seen in patients on the ICU, operating theatre, emergency department, during transport of ventilated patients and during CPR. PEEPi is easily overlooked although intensivists are trained to recognize the signs and symptoms indicating the presence of PEEPi. PEEPi can cause severe ventilatory and circulatory impairment and may be potentially life-threatening. Treatment includes, allowing sufficient time for expiration and careful appliance of extrinsic PEEP.

References 1. 2.

3. 4. 5.

6.

7. 8.

Pepe PE, Marini JJ. Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction. Am Rev Respir Dis 1982;126:166-170. Lumb A. Artificial ventilation. In: Lumb E (ed) Nunn’s Applied Respiratory Physiology. Fifth edition. Oxfort Auckland Boston Johannesburg Melbourne New Delhi. Butterworth Heineman 2000:pp 605-607. Rossi A, Polese G, Brandi G, Conti G. Intrinsic positive end-expiratory pressure (PEEPi). Intensive Care Med 1995;21:522-536. Brochard L. Intrinsic (or auto-) PEEP during controlled mechanical ventilation. Intensive Care Med 2002;28:1376-1378. Durante G de, Turco M del, Rustichini L, Cosimini P, Giunta F, Hudson LD, et.al. ARDSNet Lower Tidal Volume Ventilatory Strategy May Generate Intrinsic Positive End-Expiratory Pressure in Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2002;165:1271-1274. Connery LE, Deignan MJ, Gujer MW, Richardson MG. Cardiovascular collapse associated with extreme iatrogenic PEEPi in patients with obstructive airways disease. Br J Anaesth 1999;83:493-495. Conacher ID. Dynamic hyperinflation-the anaesthetist applying a tourniquet to the right heart. British Journal of Anaesthesia 1998;81:116-117. Maltais F, Reissmann H, Navalesi P, Hernandez P, Gursahaney A, Ranieri VM, et al. Comparison of static and dynamic measurements of intrinsic PEEP in mechani-

9. 10.

11.

12.

13. 14. 15.

cally ventilated patients. Am J Respir Crit Care Med 1994;150:1318-1324. Brochard L. Intrinsic (or auto-) positive end-expiratory pressure during spontaneous or assisted ventilation. Intensive Care Med 2002;28:1552-1554. Blanch L, Bernabe F, Lucangelo U. Measurement of Air Trapping, Intrinsic Positive End-Expiratory Pressure, and Dynamic Hyperinflation in Mechanically Ventilated Patients. Respir Care 2005;50(1):110-123. Komdeur R, van der Werf TS, Ligtenberg JJM, Tulleken JE, Zijlstra JG. Hemodynamische en ventilatoire complicaties van beademing met hoge intrinsieke positieve eindexpiratoire druk. Ned Tijdschr Geneesk 2000;144(30)1445-1450. Ranieri VM, Mascia L, Petruzelli V, Bruno F, Brienza A, Guiliani R. Inspiratory effort and measurement of dynamic intrinsic PEEP in COPD patients: effects of ventilator triggering systems. Intensive Care Med 1995;21:896-903. Lapinsky SE, Leung RS. Auto-PEEP and Electromechanical Dissociation. N Engl J Med 1996;335:674-675. Stather DR, Stewart TE. Clinical review: Mechanical ventilation in severe asthma. Critical Care 2005;9:581-587. Fernandez A, Lazaro A, Garcia A, Aragon C, Cerda E. Bronchodilators in patients with chronic obstructive pulmonary disease on mechanical ventilation. Utilization of metered-dose inhalers. Am Rev Respir Dis 1990;141(1):164-8.

16. Rubini F, Rampulla C, Nava S. Acute effect of corticosteroids on respiratory mechanics in mechanically ventilated patients with chronic airflow obstruction and acute respiratory failure. Am J Respir Crit Care Med 1994;149:306-10. 17. Ranieri VM, Guiliani R, Cinnella G, Pesce C, Brienza N, Ippolito EL, Pomo V, Fiore T, Gottfried SB, Brienza A. Physiologic effects of positive end-expiratory pressure in patients with chronic obstructive pulmonary disease during acute ventilatory failure and controlled mechanical ventilation. Am Rev Respir Dis 1993;147(1):5-13. 18. Caramez MP, Borges JB, Tucci MR, Okamoto VN, Carvalho CR, Kacmarek RM, et.al. Paradoxical responses to positive end-expiratory pressure in patients with airway obstruction during controlled ventilation. Crit Care Med;2005:33:1519-1528.



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Received January 2006; accepted in revised form July 2006

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Critical Care and Emergency Research in the European Union under the European Clinical Trials Directive 2001/20/EC:

Recommendations of the ‘VISEAR’ working group E.J.O. Kompanje Department of Intensive Care, Erasmus MC University Medical Center Rotterdam, The Netherlands

Introduction. The European Clinical trial Directive 2001/20/EC was intended to be a European-wide harmonization of the provisions concerning clinical pharmacological trials, with the focus on the facilitation of multinational clinical research [1]. Since its publication in 2001, several articles have drawn attention to the serious threat to the development of critical care and emergency research within the European Union (EU) posed by the Directive 2001/20/EC which requires prior informed written consent before subjects can be recruited to clinical trials of medicinal products [2-16]. The Directive makes no direct exceptions for critical care and emergency situations, thus threatening to prevent all trials that involve patients with acute catastrophic illness which entails the loss of decision-making capacity and very short therapeutic time windows. These include conditions such as severe shock, circulatory arrest, acute myocardial infarction, severe infectious diseases, severe stroke and other acute neurological conditions, as well as patients suffering from moderate and severe traumatic brain injury. Implementation by all EU countries was required by May 2004. The wording of the Directive permitted some flexibility so that variations were expected that might impact on emergency research. Lemaire et al [4] described the variations in national legislative responses to the Directive within Europe; they called on legislators to permit waivers of informed consent for critical care and emergency medicine research, to clarify terms and definitions, and to remove the artificial distinction between interventional and observational research. In the Netherlands, the requirements of the Directive have been transposed into the revision of the Medical Research in Human Subjects Act (WMO) and the Medicines Act (WOG) [17]. The amended WMO has changed the rules governing drug studies in the Netherlands. There is little, if any, change to non-drug-related research. The Dutch Parliament accepted the plans for the amendment of the WMO on November 22 2005 and the revised Act became effective in the Netherlands on 1 March 2006. The Directive was conceived in part to ensure that participants enrolled in research projects are given adequate information about the nature of the trials and their associated risks. Legislation to protect the interests of patients was necessary and timely. Most of the articles in the Directive were welcomed by the research community; they offer guidance and will help to maintain confidence in the probity of medical research. Unfortunately however, neither those responsible for the Directive, nor many who drafted enabling legislation within the Member States, considered the particular problems relating to research in emergency and critical care situations, where consent

Correspondence: EJO Kompanje E-mail: [email protected]

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cannot be obtained from subjects and where the need for emergency treatment does not allow time for contact with relatives or other legal representatives. Moreover, in 1996 in the United States the FDA announced a waiver of informed consent for certain types of critical care and emergency medicine research after earlier, stricter provisions had brought to a halt important progress in some critical clinical situations. This shortcoming and the variable response within European Member States to the requirements of the Directive, prompted the convening of an expert meeting in Vienna, Austria on 30 May 2005 (‘Vienna Initiative to save European Research’ [VISEAR]). This initiative was supported by the Department for Ethics in Medical Research of the Vienna Medical University, in cooperation with the European Forum for Good Clinical Practice (EFGCP), the European Clinical Research Infrastructures Network (ECRIN), and the Vienna School of Clinical Research. One of the six working groups aimed at ‘clinical trials including patients who are not able to consent; the concept of individual direct benefit from research and informed consent in case of the temporarily incapacitated patient’ (Members of this working group; Prof dr C.Wiedermann [Medical University of Innsbruck, Austria & Hospital of Bolzano, Italy], Dr K. Liddell [Faculty of Law, University of Cambridge, United Kingdom], dr E.J.O. Kompanje [Department of Intensive Care and Department of Neurosurgery, Erasmus MC University Medical Center Rotterdam, The Netherlands], Prof dr B. Vrhovac [Medical school University of Zagreb, Croatia,], dr F.J.P. Lemaire [Service de Réanimation, Hôpital Henri Mondor, Créteil, France], Prof D.K. Menon [Division of Anaesthesia, University of Cambridge, United Kingdom], Prof J. Bion [Department of Intensive Care, University of Birmingham, United Kingdom], Prof D. Chamberlain [Resuscitation Council, University of Cardiff, Wales, United Kingdom]) and dr E. Nimmesgern [Directorate Health, European Commission, Brussels, Belgium]. The final VISEAR report was presented in December 2005 [18] and was published in the Wiener Klinische Wochenschrift in April 2006 [19]. Reports with recommendations from the sixth working group (‘clinical trials including patients who are not able to consent; the concept of individual direct benefit from research and informed consent in case of the temporarily incapacitated patient’) appeared this year in Resuscitation and the Wiener Klinische Wochenschrift [20,21]. This article summarizes the recommendations made by this working group, which could be of


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interest for Dutch critical care and emergency medicine researchers conducting trials in the European Community.

Items discussed The items discussed by the working group are: 1. The implementation of the EU Directive 2001/20/EC insofar as it related to research involving adult patients unable to give consent 2. Legal, ethical and practical difficulties experienced as a result of implementation of the directive 3. Possible solutions to the problems experienced As those problems in the Directive concerning intensive care and emergency research are especially relevant to Article 5 (Clinical trials on incapacitated adults not able to give informed legal consent), these were the main focus of the VISEAR working group.

Article 5 of the Directive Article 5 of the Directive starts with the statement that: ‘In the case of other persons incapable of giving informed consent, all relevant requirements listed for persons capable of giving such consent shall apply. In addition to these requirements, inclusion in clinical trials of incapacitated adults who have not given or not refused informed consent before onset of their incapacity shall be allowed only if…’ Nine further conditions follow, four of which warrant further comment concerning critical care and emergency research: 1. Article 5 (a): “…the informed consent of the legal representative has been obtained; consent must represent the subject’s presumed will and may be revoked at any time, without detriment to the subject”. In circumstances of critical care or emergency medicine, the strict requirement to obtain prior consent from a legal representative in order to enrol incapacitated patients in clinical trials can make such research either extremely difficult or impossible to perform, especially if the intervention has to be made as a matter of urgency. The relevant clinical conditions include stroke, acute and severe coronary disease, severe and moderate head injury, severe shock, infectious diseases complicated by organ failure, and circulatory arrest. The effects of Article 5a, and its implementation in many EU Member States, seriously limits research in these groups of patients in a manner that the working group believes was unintended and is certainly undesirable. The commonly used term ‘legal representative’ is not defined in the Directive, and it was explicitly stated that it was to be determined by national law. Thus Member States understandably have differing interpretations [4]. In Austria and Germany the surrogate decisionmaker must be appointed by a judge. In Norway, the impact of the Biobank Act of 2003 is such that research involving tissue sampling (e.g. blood analysis) requires the consent of the subjects themselves [15]. Most other Member States are however less restrictive, recognizing a close or appointed relative as a legitimate representative. But even this is problematic as it erroneously assumes that there is sufficient time to obtain proper informed consent from a representative before the research can start. This is not the case in many of critical and life-threatening conditions. In one study, 83% of the European neuro-trauma centres sampled, reported that consent procedures significantly delayed the initiation of study treatment in patients with traumatic brain injury [8]. The varying interpretation of ‘legal representative’ creates difficulties for international trials where protocols and practice are expected to be uniform.

The working group emphasized the need for further work to harmonize international terminology and recommended solutions adopted in other countries. Some of the EU Member States have deferred or waived the requirement to obtain the consent of a legal representative where treatment must be started within a short time: a limit of eight hours has been suggested. This has some support in the literature. Ågård et al. found that 84% of patients with myocardial infarction were willing to allow the physician to make the decision on including them in the trial in the event of their being too ill to be asked about participation [22]. More recently, a study about consent for stroke research found that 92% of a small sample of patients thought the physician should be able to decide whether the patient is enrolled in a study if there is insufficient time to seek consent from a family member or surrogate [23]. Similarly 76% of European neuro-trauma centres (n=79) questioned the ethics of raising the issue of trial inclusion with relatives of a patient with severe traumatic brain injury so soon after admission [8]. A study in the United States by the National Acute Brain Injury Study: Hypothermia (NABIS-H) straddled a change in the law. This led to the finding that waiving the requirement for consent reduces the time to treatment by approximately 45 minutes and safely enrols a substantially larger number of patients [24]. This was highly significant for the study, which had a treatment window of less than six hours. An alternative approach adopted by some Member States is to defer the need for consent for an agreed interval either until the subject regains capacity or until a legal representative is available and able to cooperate. This is advantageous in that it responds to the problems of the consent process without eliminating the involvement of family members. Revocation of consent presents other potential difficulties. The practical implications are unclear and have caused confusion. Accepting that many treatments must be started as soon as possible if any benefit is to be obtained, and that this may inevitably precede any opportunity to consult, the question is whether or not participation can be continued. Nobody doubts a legal representative’s power to halt the administration of a medicinal product or to order that no additional data be collected. But what should be done with data collected up to that point? Bias could arise from revocation of consent by survivors whereas non-survivors would not of course be able to do so. On the other hand, survivors who are aware that they have recovered from serious illness as a result of treatment would be unlikely to withdraw consent for data to be used, whereas a relative functioning as the legal representative may well do so if treatment is unsuccessful. Bias can be averted only if data collected up to the point of withdrawal from the trial can be included in final analyses. 2. Article 5 (e): “…such research is essential to validate data obtained in clinical trials on persons able to give informed consent or by other research methods and relates directly to a life-threatening or debilitating clinical condition from which the incapacitated adult concerned suffers”. In most cases the first condition in relation to validation presents no problem. Although some forms of treatment will be appropriate only for incapacitated individuals and will therefore never be used in other clinical trials, data will always be available from animal studies or other sources. The second condition, however, that research must relate directly to a life-threatening or debilitating condition could be interpreted in an unfavourable way that the legislators may not have intended. Patients who are critically ill require a great deal of therapeutic support, including mechanical ventilation, sedation and artificial feeding. Research may indeed be required to improve adjunctive patient care. Valid and necessary studies must be permitted in order



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to improve clinical care in situations where the incapacity arises from the treatment and not from the condition. 3. Article 5 (g): “ … the Ethics Committee, with expertise in the relevant disease and the patient population concerned or after taking advice in clinical, ethical and psychosocial questions in the field of the relevant disease and patient population concerned, has endorsed the protocol”. Ethics committees are often the only arbiters of the acceptability of a research project. An ill-advised adverse decision leads to much delay or, all too frequently, to appropriate and necessary research being abandoned. The resources available to ethics committees and their degree of expertise vary appreciably within the EU and also within individual Member States. Multi-centre and international research projects may have to be submitted to several committees and different decisions are sometimes made on the same protocol. To a degree such problems reflect the lack of necessary expertise; this is understandable within a committee but many do not have systems for routinely making use of expert advice. Multi-centre committees may also require local committees to endorse their decisions, thus adding an additional layer of bureaucracy and increasing delays. Every effort should be made to simplify the process consistent with ensuring fair and appropriate decisions that safeguard the interests both of individuals and the wider population. A prerequisite for patient protection is careful and independent safety monitoring to limit risks. Current practice is that safety monitoring committees, although independent, are convened and sponsored by the pharmaceutical companies who initiate the trials, consequently leading to a potential conflict of interest. For emergency and intensive care trials, especially those conducted under waiver of consent or deferred consent, we would prefer the institution of an independent safety committee, under the auspices of regulatory authorities. 4. Article 5 (i): “ … there are grounds for expecting that administering the medicinal product to be tested will produce a benefit to the patient outweighing the risks or produce no risk at all”. There are two serious problems with this Article. The first is that the requirement that the medicinal product should be expected ‘to produce a benefit to the patient outweighing the risks or no risk at all’ is incompatible with the well-established ethical principle of equipoise. The second is that Article 5i (and the Directive as a whole) does not take into account observational research, where there can be no direct benefit to the individual patient, but there may be substantial benefit to future patients though improved understanding of diseases processes and established treatments. Equipoise is a necessary prior condition for conducting any prospective randomized trial comparing a promising but unproven therapy against an alternative treatment or placebo. This is the only mechanism for determining the risk-benefit ratio of a new treatment, and is therefore, a favourable ratio, logically cannot be a condition for performing a clinical trial. If benefit can be expected for patients in critical or emergency situations, how can a placebo group be an ethical component? Enrolling patients in a trial in which some subjects will be known from the outset to be receiving inferior treatment would be contrary to the duty of care, particularly where consent cannot be obtained because of mental incapacity. On the other hand, a randomized trial can be expected to show a worse outcome in one arm (the placebo) compared with the other, by the time it has been successfully concluded [25]. If the stipulation for risk also extends to the necessary investigations, then other problems arise. For example, who could guarantee that even simple intravenous line placement would involve no risk?

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And in a placebo arm, likely to be 50% of the trial population, how could there be benefit that would outweigh even these miniscule risks?

Conclusion The primary purpose of research is to produce knowledge that can be put into general use by those communities who have a similar clinical situation to that of those enrolled. In doing so, any risks must be weighed carefully so that participants are not put at unnecessary or disproportionate risk; there should also be at least the possibility of benefit where active treatments are administered. But the wording of Article 5 is too strong, possibly unintentionally, where it states ‘grounds to expect that [it] will produce a benefit’ and not ‘may produce a benefit’. The requirement to ascertain a favourable risk/benefit ratio should, however, be carried out in relation to the non-therapeutic components of the trial. The wording of the Directive cannot be changed but the legal implementation within Member States can still be modified to achieve the intended purpose of the Directive. It is in the interests of those who will require critical or emergency care in the future that intensivists should be prepared to do so. The situation as it now appears does not makes the European Union a particularly attractive place to do multi-national critical care research, with a negative effect on ongoing research.

Recommendations made by the working group The working group made 16 recommendations concerning ‘clinical trials including patients who are not able to consent; the concept of individual direct benefit from research and informed consent in case of the temporarily incapacitated patient’ [18]: 1. Article 5(a) should be amended as necessary (by extension, deferral or waiver) to permit and harmonize critical care and emergency research involving incapacitated persons where treatment must be commenced as a matter of urgency. 2. Member States should implement systems for legal representation that are compatible with critical illness research. Countries which ordinarily rely on court-appointed representatives should check the system is making timely appointments. 3. Countries which usually rely on family members to act as legal representatives should permit decisions to be made by other persons (unconnected with the research) when family members are too overwhelmed, or stressed to decide, or should defer or waive the consent requirement. 4. Further legal research should be undertaken to ascertain the definitions of ‘legal representative’ that apply in Member States. This could be used as a resource to ensure the lawfulness of international trials, for the basis of public debate and discussion papers, and to analyze the extent to which current definitions cause problems for research about emergency and critical illness. 5. The EC and Member States should clarify the extent of a legal representative’s power to revoke the individual’s participation in a clinical trial with reference to the future analysis for research purposes of data or tissue already collected. 6. Ethics committees should ensure that they interpret the phrase ‘research…directly related to a life-threatening or debilitating clinical condition’ in the case of critical care of emergency medicine appropriately, and not too narrowly. The interpretation should permit research in conditions accompanied by incapacity, research in settings where incapacity is the consequence of essential therapy, research that addresses the common complications of incapaci-


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tating conditions, and research to improve methods of supportive therapy. 7. The EC and Member States should increase the resources available for Ethics Committees to secure members or advisors with specialist knowledge relevant to clinical trials with incapacitated patients. 8. The EC and Member States should develop centralized bodies, guidelines and records of precedent decisions for ethics committees to increase the efficiency, consistency and predictability of their decisions. 9. The EC and Member States should recognize that in circumstances of clinical equipoise there will be substantial uncertainty whether administering a medicinal product will benefit a patient. The requirement that the trial be expected to produce benefits outweighing risks (or no risk at all) must be interpreted in this light. 10. The EC and Member States should publish guidance about ‘component analysis’ to clarify that when assessing whether a trial will produce a benefit to the patient outweighing the risks (or no risk at all), the judgment should be made with reference to the benefits and risks associated with the research component of the trial (rather than components of the trial that reflect accepted medical therapies or treatments in equipoise). 11. In conjunction with component analysis, the EC and Member

States should review or clarify the requirement that the trial produce “a benefit to the patient outweighing the risks or produce no risk at all”. This should allow a protocol to include non-therapeutic components (e.g. scans, chart checks, blood tests) of no benefit to the individual, provided they represent no more than minimal risk, are minimized and proportionate to the knowledge gained. 12. When national legislation implementing the Directive covers more than clinical drug trials, Member States should ensure it permits research with no therapeutic benefit for the individual provided it poses them no more than minimal risk (for example observational studies, research using human tissue samples). 13. Researchers should document instances where non-therapeutic research has been unwisely prohibited by inappropriate implementation or extension of the Directive. 14. The EC and Member States should support ethical and legal research to develop guidelines for difficult risk comparisons. 15. Member States should monitor the impact of their laws on research involving incapacitated patients, particularly Member States which have applied the conditions of the Clinical Trials Directive to medical research other than clinical drug trials. 16. The EC and Member States should publish guidance to assist researchers and ethics committees with the interpretation of the Directive and implementing legislation.

References 1.

2. 3. 4.

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Directive 2001/20/EC of the European Parliament and the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Off J Eur Comm 2001: L 121-134. Visser HKA. Non-therapeutic research in the EU in adults incapable of giving consent? The Lancet 2001; 357: 818-819. Baeyens AJ. Implementation of the Clinical Trials Directive: pitfalls and benefits. Eur J Health Law 2002; 9: 31-47. Lemaire F, Bion J, Blanco J, Damas P, Druml C, Falke K, et al. The European Union Directive on Clinical Research: present status of implementation in EU member states’ legislation with regard to the incompetent patient. Intensive Care Med 2005;31:476-479. Stertz F, Singer EA, Böttiger B, Chamberlain D, Baskett P, Bossaert L, Steen P. A serious threat to evidence based resuscitation within the European Union. Resuscitation 2002;53:237-8. Kompanje EJO, Maas AIR, Dippel DWJ. Klinisch geneesmiddelenonderzoek bij acuut beslissingsonbekwame patiënten in de neurologie en de neurochirurgie; implicaties van nieuwe Europese regelgeving. Ned Tijdschr Geneeskd 2003; 147: 1585-1589. Kompanje EJO, Maas AIR. ‘Treat first, ask later?’ Emergency research in acute neurology and neurotraumatology in the European Union. Intensive Care Med 2004; 30: 168-169. Kompanje EJO, Maas AIR, Hilhorst MT, Slieker FJA, Teasdale GM. Ethical considerations on consent procedures for emergency research in severe and moderate traumatic brain injury. Acta Neurochir 2005; 147: 633-640.

9. Silverman HJ, Druml C, Lemaire F, Nelson R. The European Union Directive and the protection of incapacitated subjects in research: an ethical analysis. Intensive Care Med 2004; 1723-1729. 10. Singer EA, Druml C. Collateral damage or apocalypse now for European academic research. Intensive Care Med 2005; 31: 271. 11. Lemaire FJP. A European Directive for clinical research. Intensive Care Med 2003; 29: 1818-1820. 12. Lemaire F. Waiving consent for emergency research. Eur J Clin Investig 2005; 35: 287-289. 13. Druml C. Informed consent of incapable (ICU) patients in Europe: existing laws and the EU Directive. Curr Opin Crit Care 2004; 10: 570-573. 14. Truog RD. Will ethical requirements bring critical care research to a halt? Intensive Care Med 2005; 31: 338344. 15. Klepsted P, Dale O. Further restrictions for ICU research. Intensive Care Med 2006; 32: 175 16. Larsson A, Tønnesen E. ICU research in Denmark: difficult but possible. Intensive Care Med 2006; 32: 934 17. The Working party for implementation of Directive 2001/20/EC. Clinical Research with medicinal products in the Netherlands. Ministry of Health, Welfare and Sport, 2005. 18. Report of the 1st Meeting of the “Vienna Initiative to Save European Academic Research (VISEAR)” organised by the Medical University of Vienna Department Ethics of Medical research, in collaboration with the European Forum for Good Clinical Practice (EFGCP), the European Clinical Research Infrastructures Network (ECRIN), and the Vienna School of Clinical Research (VSCR), December 2005. 19. Druml C, Singer EA, Wolzt M. Report of the 1st Meeting of the “Vienna Initiative to Save European Academic

20.

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23. 24. 25.



Research (VISEAR)”. Wien Klin Wochenschr 2006; 118 [Suppl.]: 1-12 Liddell K, Chamberlain D, Menon DK, Bion J, Kompanje EJO, Lemaire F, Druml C, Vrhovac B, Wiedermann CJ, Sterz F. The European Clinical trials Directive revisited: the VISEAR recommendations. Resuscitation 2006; 69: 9-14 Liddell K, Kompanje EJO, Lemaire F, Vrhovac B, Menon DK, Bion J, Chamberlain D, Wiedermann CJ, Druml C. Recommendations in relation to the EU Clinical Trials Directive and medical research involving incapacitated adults. Wien Klin Wochenschr 2006; 118: 183-191 Ågård A, Hermerén G, Herlitz J. Patients experiences of intervention trials on the treatment of myocardial infarction: is it time to adjust the informed consent procedure to the patients capacity? Heart 2001; 86: 632-637. Blixen CE, Agich GJ. Stroke patients preferences and values about emergency research. J Med Ethics 2005; 31: 608-611. Clifton GL, Knudson P, McDonald M. Waiver of consent in studies of acute brain injury. J Neurotrauma 2002; 19: 1121-1126. Freeman DB. Safeguarding patients in clinical trials with high mortality rates. Am J Crit Care Med 2001; 164: 190-192

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Received March 2006; accepted in revised form July 2006

o r i g i n a l

Dexamethasone in paediatric cardiac surgery; implications using two surrogate markers I. Malagon1, W. Onkenhout2, J.G. Bovill1, M.G. Hazekamp3 1Department of Anaesthesia, 2Department of Paediatrics, 3Department of Paediatric Cardiac Surgery Leiden University Medical Centre The Netherlands

Abstract. The use of steroids in cardiac surgery remains controversial. In adult cardiac surgery there are studies showing a clear benefit, no benefit at all, and in some even detrimental effects. While there seems to be consensus that steroids should be used in paediatric cardiac surgery, there is no clear agreement over which drug should be used, in what dosage and how many times around the operation. We have studied the effect of dexamethasone during cardiac surgery using two surrogate markers; gut permeability and cardiac troponin T. In this article we present our results together with a short historical review.

Introduction and historical perspective Steroids have been used in cardiac surgery for nearly fifty years. After all this time its use remains controversial. A recent postal survey showed that although the majority of the institutions surveyed used steroids in paediatric cardiac surgery, there is lack of agreement over which drug, what dosage should be used and how many times should be prescribed [1]. Following animal studies carried out in the 1960s, methylprednisolone became the drug of choice in adult cardiac surgery because of its anti-inflammatory potency and minimal tendency to induce sodium and water retention. An intravenous dose of 30 mg/kg was considered optimal because clinical studies had shown to be beneficial [2], yet caused no detrimental effects when administered to a small group of healthy volunteers [3]. A landmark study published in 1970 by Dietzman and colleagues [4] reported that methylprednisolone (30 mg/kg) was effective in treating the low cardiac output syndrome in dogs and humans following cardiac surgery. In 98 dogs, methylprednisolone administration decreased systemic vascular resistance, increased cardiac index, improved tissue perfusion, and increased survival from 22 to 65%. In 19 humans following cardiac valve replacement the same beneficial haemodynamic effects were observed. In the early 1980s the pivotal role that complement activation played in the basic physiological insults caused by CPB was demonstrated. This triggered a number of investigations focusing on the effect of steroids on post-bypass complement activation and cytokines production. An overwhelming number of these studies demonstrated that the use of steroids was associated with a considerable reduction of proinflammatory cytokines production in the postoperative period, although the complement activation was not affected [5]. However we had to wait another decade to see investigators moving away from biochemical parameters and focusing on clinical outcome. In 1999 Tassani and colleagues [6] showed that patients given methylprednisolone had better haemodynamic parameters in the postoperative period although extubation time was not affected. More recently, Yared and colleagues [7] reported, in a study involving

Correspondence: I. Malagon E-mail: [email protected]

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more than 200 patients, that giving dexamethasone before starting CPB was associated with earlier tracheal extubation than the placebo group. In contrast to these two previous studies Chaney and colleagues [8,9] demonstrated in two prospective randomized trials that the use of methylprednisolone was associated with delayed tracheal extubation and was not associated with any haemodynamic improvements. In paediatric cardiac surgery the use of steroids has not been investigated to the same extent as in adults, and its use is as controversial. Lindberg and colleagues [10] considered that it was unethical not to use dexamethasone in children weighing less than 10 kg scheduled for cardiac surgery. Dexamethasone appears to reduce postoperative troponin I production [11]. It has also been shown to reduce the production of C-reactive protein without any effect on the release of protein S100B and Von Willebrand factor [10]. The concentration of proinflammatory cytokines decreases when steroids are used before starting CPB [12]. The reduction is even more remarkable if steroids are given before and during CPB [13]. Oxygen delivery and cardiac output improve faster when steroids were used in an animal model [14]. Even the timing of the administration seems to be relevant [15]. However, when clinical end points have been used to test the benefits of steroids the results are not so impressive [16]. Our aim was to investigate how dexamethasone could influence the side effects associated with CPB in two organs, the small intestine and the heart. To that purpose we chose two surrogate markers, gut permeability and cardiac troponin T production.

The dual sugar permeability test in paediatric cardiac surgery Intestinal mucosal ischaemia, although transient, can occur in infants and children during and after CPB [17]. Severe decreases in mucosal perfusion may be a causative factor for postoperative mortality or complications such as necrotizing enterocolitis (NEC). Neonates with aortic arch anomalies and infants subjected to CPB-induced profound hypothermia may be at particular risk of developing splanchnic ischaemia in the perioperative period [18]. These studies used indirect indicators of intestinal mucosal perfusion (e.g. laser Doppler probe or gastric tonometry). Patients with coarctation of the aorta may, on the other hand, be exposed to reperfusion injuries after the surgical repair, manifesting as the postcoarctectomy syndrome [19]. The dual sugar permeability test (DSPT) to assess gut permeabil-


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Table 1: Patient characteristics. Values expressed as median (95% confidence intervals). No CPB CPB P value 17 17 Number of patients Age (months) 2 (0.2-24) 5 (2-47) 0.17 Sex (M/F) 8/9 6/11 0.72 Weight (kg) 4.8 (2.5-15) 6 (4-14) 0.24 Surgery time (min) 83 (45-160) 73 (176-360) 0.01 0 105 (73-202) Bypass time (min) Aortic clamp time (min) 0 (0-21) 73 (0-150) Ventilator hours 24 (6-144) 48 (24-168) 0.11

ity was introduced in the 1970s to overcome the problems associated with the use of single markers [20]. After thirty years it has stood the test of time and remains in use for clinical and research purposes. Gut permeability had not been investigated in paediatric patients undergoing cardiac surgery. Intestinal permeability can be evaluated noninvasively by measuring the urinary excretion of orally administered water-soluble, nondegradable test molecules [21,22]. This barrier function test is based on the comparison of intestinal permeation of larger molecules with that of smaller molecules by measuring the ratio of their urinary excretion. These two types of molecules follow different routes of intestinal permeation: the larger molecules are assumed to permeate paracellularly, and the smaller molecules transcellularly. Preabsorption factors such as gastric emptying, dilution by secretion and intestinal transit time, and post-absorption factors such as systemic distribution and renal clearance are assumed to affect both molecules equally. Four saccharides, 3-O-methyl-D-glucose (molecular weight 194 Da), D-xylose (molecular weight 150 Da), L-rhamnose (R, molecular weight 164 Da) and lactulose (L, molecular weight 342 Da) are employed to assess active carrier-mediated, passive carriermediated, transcellular, and paracellular transport, respectively in the small intestine. Intestinal permeability is considered to be normal if the lactulose (% recovery)/rhamnose (% recovery) (L/R) ratio is below 0.05 [21]. Intestinal absorptive capacity for saccharides is considered to be normal when the recoveries of D-xylose (passive carrier-mediated transport) and 3-O-methyl-D-glucose (active carrier–mediated transport) are around 10% and 30% respectively [23]. The accuracy of the DSPT relies on the complete collection of urine samples during the study period. This is a limiting factor on the applicability of the test in non-cooperative patients without a urinary catheter. A high percentage of patients are discharged to the ward the day after surgery with the consequent removal of urinary catheters. For this reason we performed the test during the first 24 hours after the operation. There has been criticism concerning the interpretation and significance of the DSPT in the literature [24,25]. In an animal model it was shown that fluid loading increased the L/R ratios independent of changes in intestinal permeability. Over an 8-hour period rats received in a fluid bolus equivalent to twice the daily fluid oral intake. Put into perspective, this means an infant of 10 kg would receive approximately 2 litres fluid intravenously over an 8-hour period. We carefully documented the fluid balance during the study period. On average patients received less than the daily maintenance fluid expected for their age. There are other limiting factors which affect the use of the DSPT. The type of sugars must be chosen carefully. Mannitol is present in some blood products and is part of the prime during CPB. The test

Table 2: Type of operations performed in each group. Atrioventricular septal defect (AVSD). Mitral valve anuloplasty (MVA). Total anomalous pulmonary venous connection (TAPVC). Tetralogy of Fallot (ToF). Ventricular septal defect (VSD). No CPB CPB 1 Coarctation of the aorta 7 Aortic stenosis Banding pulmonary artery 3 AVSD 2 Blalock-Taussig shunt 7 Glenn 2 MVA 2 TAPVC 2 ToF 1 VSD 7 Total 17 17 Table 3: Lactulose/rhamnose ratios (L/R) and percentage recovery for lactulose, rhamnose, 3-O-methyl-glucose (3OMG) and xylose without and with cardiopulmonary bypass (CPB). Values are expressed as median (95% confidence intervals). * Denotes statistical significance between groups. † Denotes statistical significance within groups. T0 T12 T24 L/R No CPB 0.39 (0.07-1.8) 0.22 (0.03-0.85) 0.11 (0-0.48) CPB 0.30 (0.02-2.6) 0.32 (0.07-6.9) 0.24 (0.05-3.2)* Lactulose No CPB 0.18 (0.02-0.73) 0.35 (0.01-1.2) 0.41 (0.2-0.92)† CPB 0.03 (0.01-0.3)* 0.29 (0.07-1.76) 0.82 (0.05-3.32) † Rhamnose No CPB 0.29 (0.04-1.56) 1.56 (0.12-11.1) 3.64 (1.2-17.6) † CPB 0.08 (0.03-1.14)* 1.17 (0.06-4.23) 3.8 (0.04-18.1) † 3OMG No CPB 0.64 (0.11-9.21) 3.9 (0.11-25.34) 14.1 (2.2-55.3) † CPB 0.19 (0.04-1.88)* 1.31 (0.1-12.93) 7.4 (0.03-48.6)† Xylose No CPB 0.72 (0.17-2.89) 1.34 (0.27-14.81) 3.3 (0.92-38.31) † CPB 0.2 (0.04-1)* 0.73 (0.07-7.3) 2.1 (0.04-18.14) †

can produce spurious results as we found out in one of our studies (26). Finally, it has been assumed that rhamnose is an inert sugar not metabolized by the human body. We found increased concentrations of rhamnitol (a metabolite of rhamnose) in the urine samples of 34 paediatric patients undergoing the DSPT and in an adult volunteer. This may be an indication that rhamnose is not an inert sugar after all [27]. Before examining the effect of dexamethasone on gut permeability we first had to evaluate the changes in intestinal permeability during the perioperative period in patients undergoing surgery with and without cardiopulmonary bypass. Thirty-four patients undergoing cardiac surgery were investigated. Demographic data and type of operations are presented in tables 1 and 2 respectively. Our study showed [28] that from the outset L/R ratios (Table 3) were well above the normal values expected in patients of similar age without cardiac defects. Patients undergoing surgery without CPB showed a progressive improvement in L/R ratios, while in those with CPB the L/R ratio either deteriorated or did not improve. Only patients undergoing repair of coarctation of the aorta had near normal L/R ratios 24 h after the surgical procedure. Proinflammatory cytokines have a deleterious effect on the intestinal barrier when studied in vitro [29]. In the same in vitro model, when the intestinal mucosa is exposed to anti-inflammatory cytokines, the gap between the epithelial cells of the intestinal mucosa improves [30]. Animal studies have shown that steroids accelerate the maturation and stimulate the growth of the intestinal mucosa in ex-premature animals and it has long been accepted that steroids given to the pregnant mother reduce the risk of NEC in the premature baby. The effect of dexamethasone on gut permeability when administered during induction of anaesthesia in paediatric patients undergo-



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Table 4: Lactulose/rhamnose ratios (L/R) and percentage recovery for lactulose, rhamnose, D-xylose and 3-O-methyl-glucose (3OMG) without and with dexamethasone. Values are expressed as mean (95% confidence intervals). P values represent statistical significance between groups using repeated measures ANOVA. T0 T12 T24 P value L/R ratios No dexamethasone 0.57 (0.24 – 0.91) 0.77 (0 – 1.64) 0.46 (0.06 – 0.85) Dexamethasone 0.76 (0.35 – 1.17) 0.29 (0.17 – 0.42) 0.17 (0.08 – 0.15) 0.019 Lactulose No dexamethasone 0.07 (0.02 – 0.12) 0.31 (0.22 – 0.4) 0.87 (0.51 – 1.23) Dexamethasone 0.08 (0.02 – 0.14) 0.62 (0.34 – 0.89) 1.07 (0.11 – 2.04) 0.056 Rhamnose No dexamethasone 0.16 (0.02 – 0.30) 1.44 (0.68 – 2.2) 4.59 (2.23 – 6.94) Dexamthasone 0.16 (0.02 – 0.31) 3.02 (1.36 – 4.69) 6.18 (3.35 – 9) 0.047 D-xylose No dexamethasone 0.29 (0.14 – 0.45) 1.58 (0.42 – 2.75) 5.69 (2.41 – 8.96) Dexamethasone 0.34 (0.08 – 0.60) 2.96 (1.83 – 4.09) 5.47 (2.59 – 8.34) 0.056 3OMG No dexamethasone 0.38 (0.12 – 0.64) 3.37 (1.21 – 5.54) 14.42 (6.19 – 22.6) Dexamethasone 0.33 (0.09 – 0.57) 7.32 (3.32 – 11.33) 13 (6.59 – 19.42) 0.041

ing cardiac surgery with cardiopulmonary bypass was subsequently studied [31]. The results confirmed what had been already shown in in vitro studies; although the mechanism is not clear, dexamethasone reduces gut permeability when given before CPB starts (Table 4). Neonates with a hypoplastic left heart syndrome (HLHS) undergoing stage I of the Norwood operation are at higher risk of intestinal ischaemia in the perioperative period. In these patients the systemic and pulmonary circulations depend on one functioning ventricle. This can expose the patient to periods when there is an imbalance between the systemic and pulmonary circulations, with excessive pulmonary flow to the detriment of mesenteric perfusion. The surgical procedure requires a period of deep hypothermic circulatory arrest (DHCA), adding an extra insult to the mesenteric circulation. NEC is relatively uncommon in children undergoing cardiac surgery, however mortality is nearly 100% in patients with hypoplastic left heart syndrome [32]. In a recent retrospective study [33] of 107 patients undergoing stage 1 of the Norwood procedure, NEC occurred in 21% of the patients with 38% mortality. However, gastrointestinal complications (NEC, enteral feeding at discharge, gastroesophageal reflux, and prolonged hospital stay due to feeding difficulties) were present in 48% of the study population. With this data in mind, it comes to no surprise that investigators assessing flow in the superior mesenteric artery of HLHS patients found diastolic flow reversal before and shortly after stage 1 of the Norwood procedure [34]. It had been common practice at our institution to use steroids only in patients requiring a period of DHCA. We felt that preoperative and intraoperative insults to the intestinal mucosa in this group of patients warranted a separate investigation. Seven patients undergoing stage 1 of the Norwood procedure were investigated [26]. Gut permeability as assessed by the DSPT was abnormal in patients with HLHS up to 24 hours after surgery (Table 5). Of the seven patients investigated, six had uneventful stays in the intensive care unit, and were mechanically ventilated for between two and five days. Patient 4 died of NEC three days after the surgical procedure. Patient 5 was readmitted to the paediatric intensive care unit thirteen days after discharge with severe cardiac failure requiring cardiopulmonary resuscitation, which was unsuccessful. The cause of the cardiac failure was never diagnosed although severe sepsis was suspected. L/R ratios 46 times the normal value reflect a highly permeable small intestine. This may be a sign of a low output state and may help to identify patients at risk of developing NEC.

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Pre-emptive treatment of NEC before obvious clinical signs appear could have benefits in terms of morbidity and/or mortality.

Cardiac troponin T in paediatric cardiac surgery Cardiac troponin T (cTnT) is a specific marker of myocardial infarction [35]. It is also a reliable marker of myocardial injury in the paediatric population [36]. Preliminary data indicate that cTnT values shortly after surgery for congenital heart disease are potentially useful prognostic indicators of postoperative recovery [37,38]. Both cardiac troponin I (cTnI) and cTnT seem to evolve in a similar way after paediatric cardiac surgery [39]. Reported baseline values for cTnT in paediatric patients before surgery remain below the standard cut-off point of 0.1 ng ml-1. Some concerns have been raised regarding the use of cTnT in patients with chronic renal failure [40]. False pathological values of cTnT in patients with renal failure make cTnI theoretically a better choice. However cTnI also has its limitations. Sasse and colleagues [41] showed that for up to nine months after birth in healthy infants, and for up to two years in infants with congenital heart disease, cTnI is not expressed solely in the myocardium. Slow twitch skeletal muscle troponin I is expressed in variable amounts in these infants. Atriotomy [42] and ventriculotomy [43] influence cTnI production independent of myocardial damage related to other factors. Before we investigated the effect of dexamethasone on postoperative release of cTnT another issue had to be addressed. The anaesthetic agent used during the surgical procedure could influence cTnT concentrations postoperatively. Several studies have demonstrated that sevoflurane and other volatile anaesthetics reduce the postoperative production of cardiac troponin I when compared to other anaesthetic agents in adult patients undergoing coronary graft surgery [44,45]. The theoretical explanation for this benefit can be found in the process of anaesthetic preconditioning. Exposing the adult myocardium to brief periods of ischaemia and reperfusion induces greater tolerance to a subsequent, more prolonged ischaemic insult, a phenomenon known as ischaemic preconditioning (IP). Animal experiments have shown that inhalational anaesthetics, morphine, and possibly other opioids mimic the effects of IP. This is often referred to as anaesthetic preconditioning. Our study showed [46] that the postoperative production of cTnT in paediatric patients undergoing cardiac surgery is similar with


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Table 5: Lactulose/Rhamnose (L/R) ratios during the three study periods. Missing values are due to the volume of urine being too small to perform the test. Patient 4 developed NEC postoperatively. L/R Ratios Bypass (min) Arrest (min) Clamp (min) T0 T12 T24 Patient 1 0.18 0.08 0.22 300 80 270 Patient 2 1.55 0.63 0.19 180 80 80 Patient 3 0.04 0.14 0.11 162 65 87 Patient 4 2.30 238 96 92 Patient 5 27.6 2.37 0.23 345 150 174 Patient 6 0.20 0.57 0.23 140 26 71 Patient 7 0.25 0.33 180 88 88 Table 6: Cardiac troponin T concentrations (ng ml-1) in blood immediately after admission to PICU and at 8, 15 and 24 h after admission. Values are expressed as mean (95% confidence intervals). T0 T8 T15 T24 Midazolam 1.9 (1.5 – 2.3) 2.7 (1.9 – 3.5) 2.4 (1.8 – 2.9) 1.9 (1.5 – 2.3) Propofol 1.9 (1.4 – 2.4) 2.6 (1.7 – 3.5) 2.3 (1.5 – 3.1) 2.1 (1.3 – 2.8) Sevoflurane 1.7 (1.3 – 2.1) 1.7 (1.3 – 2.2) 1.6 (1.2 – 1.9) 1.5 (1.2 – 1.8) Table 7: Cardiac troponin T concentrations (ng ml-1) in blood immediately after admission to PICU and at 8, 15 and 24 h after admission. Values are expressed as mean (95% confidence intervals). * Denotes statistical significance difference between groups. T0 T8 T15 T24t No Dexamethasone 2 (1.56 – 2.51) 3.1 (2.5 – 3.7) 2.6 (2.1 – 3.2) 2.3 (1.7 – 2.7) Dexamethasone 1.84 (1.55 – 2.15) 2 (1.5 – 2.4)* 1.9 (1.5 – 2.4) 1.8 (1.3 – 2.3)

midazolam, propofol or sevoflurane anaesthesia (Table 6). Peak concentrations of cTnT 2.7 (1.9 – 3.5) ng ml-1 (mean (95 % Confidence Intervals)) are similar to those reported in other studies. Immer and colleagues [36,37] reported mean cTnT concentrations of 4.06 ng ml-1 and 5.5 ng ml-1 in two consecutive studies with a patient population similar to ours. Hovels-Gurich and colleagues [38] reported a mean value of 5 ng ml-1 in neonates with transposition of the great arteries undergoing arterial switch operation. However all these patients underwent surgery with circulatory arrest. Seven patients in our study underwent a similar period of circulatory arrest, with a maximum cTnT concentration at T8 of 3.9 ng ml-1. If IP occurs in children, sevoflurane seems to lack the IP-like effect demonstrated in the adult population [44]. Propofol and sevoflurane may provide protection to the adult myocardium by different mechanisms. However, they both appeared equally effective in our study. A possible consequence of the systemic inflammatory response syndrome related to the use of CPB is myocardial damage. This can manifest itself as a low output syndrome with a need for high inotropic support in the postoperative period. Concentrations of cTnT rise up to three fold postoperatively in children undergoing cardiac surgery when compared to adults undergoing coronary bypass surgery [47]. When cTnT was used as an end point to test the effect of dexamethasone on myocardial protection [48], patients receiving dexamethasone before CPB had lower concentrations of cTnT in the postoperative period (Table 7). Differences between the two groups were statistically significant (p < 0.035). Both groups had comparable cTnT concentrations on PICU admission (T0); 2 (1.56 – 2.51) ng ml-1 in the group without dexamethasone and 1.8 (1.54 – 2.14) ng ml-1 in the group given dexamethasone. However, subgroup analysis demonstrated that only at 8 h after admission, the cTnT concentrations were significantly higher (p < 0.005) in the non-dexamethasone group (3.1 (2.5 – 3.7) ng ml-1) than in the dexamethasone group (1.9 (1.5 – 2.4) ng ml-1). There were no significant differences in the cTnT concentrations between the groups at the other times. cTnT concentrations

at T15 were 2.65 (2.12 – 3.19) ng ml-1 in the non-dexamethasone group and 1.95 (1.46 – 2.43) ng ml-1 in the dexamethasone group. At T24 were 2.27 (1.77 – 2.76) ng ml-1 in the non-dexamethasone group and 1.81 (1.33 – 2.28) ng ml-1 in the dexamethasone group. Despite these differences we could not find any reduction in ventilator hours or inotropic support in those patients receiving dexamethasone. Checchia and colleagues [11] investigated the effect of dexamethasone (1 mg kg-1) on the postoperative production of cTnI in 28 paediatric patients undergoing cardiac surgery with CPB. They found a statistically significant reduction in cTnI concentrations 24 h after surgery in patients who received dexamethasone compared to those given a placebo. In our study we did not find any difference on the cTnT concentrations 24 h after the surgical procedure between the two groups. Other investigators have found that cTnT peaked at 4 hours after CPB [38], 30 minutes after CPB [49] and 2 hours after declamping [50]. It is not clear why cTnT concentrations peaked 8 h after admission to the PICU in our patients. A beneficial effect of steroids on cTnI degradation has been demonstrated [51]. However this study was performed in animals subjected to a 2 hour period of deep hypothermic circulatory arrest (DHCA) and methylprednisolone was given twice, 6 hours before and immediately before CPB started. Imura and colleagues [52] showed an age-dependent and hypoxia-related difference in myocardial injury during CPB. Other investigators [49] have also noted that cyanotic patients have higher cTnT concentrations postoperatively than the acyanotic counterparts. Reperfusion injury may explain this phenomenon. When CPB starts, cyanotic patients are suddenly exposed to normoxic concentrations of oxygen. According to our results [48], cyanotic patients do not shown any improvement in the postoperative production of cTnT when dexamethasone is used. The neonate myocardium has a distinct systemic inflammatory response to CPB, with higher production of proinflammatory cytokines compared to older patients [53]. We could not find any improvement in cTnT production in neonates treated with dexamethasone.



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Bronicki and colleagues [54] found a significant reduction on postoperative fluid requirements in the paediatric cardiac surgical patients (n = 15) who received dexamethasone compared to the placebo group (n = 14). The timing and amount of dexamethasone was similar to our study design. We were unable to reproduce this finding in our study of 140 patients [48]. In conclusion, the use of dexamethasone is related to a reduction in production of cTnT in the postoperative period. This reduction is however limited in time and is not associated with a significant reduction in ventilator hours or inotropic requirements in the first 24 hours after surgery.

Conclusions

There is no clear reproducible and compelling clinical evidence to suggest that the use of corticosteroids is associated with a significant improvement in morbidity and/or mortality in paediatric cardiac surgical patients. Our results add to the ongoing discussion. Intestinal permeability is elevated in paediatric patients undergoing surgery with CPB. Steroids do clearly reduce gut permeability in the postoperative period as assessed by the dual sugar permeability test. Since intestinal complications in this group of patients are relatively rare, a sufficiently powered study to test the benefits of dexamethasone using intestinal complications as an end point would be difficult, if not impossible. However, mortality related to intestinal complications in paediatric cardiac surgery is so high that even circumstantial evidence should tip the balance towards the standard use of steroids. The interpretation of the DSPT results is not straightforward. An increase in L/R ratios (or other combination of sugars) represents an

increase in intestinal permeability. Although the majority of investigators agree with this concept it is not without critics and limitations as we have already seen. Increased intestinal permeability has been demonstrated in critically ill patients with severe trauma, burns and cirrhosis. Establishing a correlation between increased intestinal permeability and multi-organ failure or increased morbidity and/or mortality is even more difficult. Again in this area there is conflicting evidence. A number of studies in this subject show contradicting results. The issue has been reviewed recently [55,56]. Steroids reduce the production of pro-inflammatory mediators or improve the pro/anti inflammatory ratios in cardiac surgical patients. Troponins have become a gold standard to identify myocardial damage in clinical practice. There is an increased production of cTnT or cTnI in the postoperative period in paediatric cardiac surgical patients. Of interest is that the peak of cTnT varied between studies. This may be due to methodological differences between investigations. While animal studies demonstrate a protective effect of steroids on the myocardium using troponins as end point, clinical studies are not conclusive. Perhaps steroids do provide myocardial protection that troponins are not able to disclose in the clinical setting. Use of steroids in paediatric cardiac surgery varies between institutions in the Netherlands. The evidence so far is that steroids do not appear to cause any harm. Further research is obviously necessary, but perhaps most important of all is that we should remain critical of extrapolating data from studies in adult patients to the paediatric population.

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16-08-2006 12:54:57


16-08-2006 12:55:05

Kom 22 september 2006 naar de

Trainingsdag Visiteurs IC Kwaliteitsvisitaties! Locatie: Hotel- en Congrescentrum De Reehorst te Ede Tijdstip: 09.30 uur - 12.30 uur

ant w o o r d f o r mu l i e r Naam Specialisatie Naam ziekenhuis Postadres Postcode / plaats g

man

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Functie Telefoonnummer Faxnummer E-mail adres g

Ik kom naar de training voor IC kwaliteitsvisitateurs op 22 september 2006

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Ontvangt hiervoor graag reiskostenvergoeding

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Ik bestel een dagretour treinkaartje. (De Reehorst ligt naast het NS Intercity station Ede-Wageningen).

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Ik maak graag gebruik van de lunch om 12.30 uur.

Wilt u dit antwoordformulier sturen aan NVIC, secretariaat visitatie, Stationsweg 73 C, 6711 PL te Ede / tel. 0318-693337 / fax 0318-693338 / Email: [email protected] U kunt ook gebruik maken van het gratis antwoordnummer: NVIC secretariaat visitatie Antwoordnummer 2459 6710 WB Ede


16-08-2006 12:55:06

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C. C . rugo C. gla b s a C. pararata C. trop p s i l o C. krusicali sis s C . gui l e i l l i C. i p o e r m l C. d u b y t i c o n d l a ii C. kefy inie lu r ns is sit an A. iae A. flav u A . f um s i A. terr gat u e A . nige u s s ni r du lan s

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Referenties: 1. Duarte P.N.: Comparison of caspofungin and amphotericin B for invasive candidiasis. N Eng J Med 347;2020-9, 2002. 2. Maertens J.: Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant for conventional antifungal therapy. CID 2004;39:000-000. 3. Walsh T.J.: Caspofungin versus Liposomal Amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Eng J Med 2004; 351:1391-402. 4. David W. Denning: Echinocandin antifungal drugs. The Lancet 362: 1142-51, 2003. Raadpleeg eerst de volledige productinformatie alvorens CANCIDAS voor te schrijven CANCIDAS is een geregistreerd handelsmerk van Merck & Co., Inc., Whitehouse Station, NJ, USA

M Merck Sharp & Dohme BV, Postbus 581, 2003 PC Haarlem, Tel. 023-5153153, www.msd.nl, www.univadis.nl

Cans155J_Adv_210x277.indd 1 NJCC_04 binnenwerk 01.indd 512

Evidence. Experience. Confidence. 09-06-2006 12:55:08 11:21:37 16-08-2006


Verenigingsnieuws Procedure verkiezing nieuwe voorzitter en bestuursleden

S

S

Enige tijd geleden heeft het bestuur van de NVIC zijn leden opgeroepen zich aan te melden als kandidaat-bestuurslid voor de NVIC. Het is verheugend te constateren dat dit inmiddels heeft geresulteerd in een aanzienlijke kandidatenlijst. Op dit moment hebben wij ook contact met een aantal kandidaten voor het voorzitterschap van de NVIC. Uit deze contacten zal een kandidaat worden geselecteerd die de officiële, door het bestuur voorgedragen, kandidaat-voorzitter zal zijn. Deze kandidaat-voorzitter zal vervolgens mede worden betrokken bij de keuze van de overige kandidaat-bestuursleden. Het bestuur gaat er vanuit dat er begin september meer duidelijkheid zal zijn met betrekking tot een kandidaat-voorzitter. In de loop van september zullen vervolgens gesprekken worden gevoerd met de overige kandidaat-bestuursleden. Een en ander heeft tot gevolg dat de officiële kandidaten voor de verschillende bestuursfuncties in principe bekend zullen worden gemaakt tijdens de geplande discussieavond over de herregistratie van intensivisten op 21 september aanstaande, en dat hierover door u gediscussieerd en gestemd zal kunnen worden op de algemene ledenvergadering van 30 november aanstaande .. In de hoop u hiermee voldoende te hebben geïnformeerd verblijf ik met vriendelijke groet, namens het NVIC bestuur, JHJ Meeder, secretaris

Accreditatie en herregistratie in beweging; wat zijn de gevolgen voor intensivisten? De afgelopen maanden is, na initiatief van de NIV, de NVOG, de NVP en de NVK, een geheel nieuw systeem opgezet voor accreditatie en herregistratie van medisch specialisten. Eerder dit jaar heb ik samen met Johan Damen reeds aangegeven dat de regelgeving voor accreditatie en daarmee herregistratie zijn veranderd (NJCC nr 1 2006, 32). Inmiddels is door de eerder genoemde verenigingen een systeem ontwikkeld dat de naam GAIA (Gemeenschappelijke Accreditatie Internet Applicatie) heeft gekregen. Het doel hiervan is tweeledig; ten eerste het centraal afhandelen en verwerken van accreditatie aanvragen van zowel commerciële als wetenschappelijke organisaties; ten tweede de centrale archivering van

e. 11:21:37

de aanvragen én van de door de individuele specialist gevolgde nascholing. Aan een dergelijk systeem zitten voor en nadelen zoals een inmiddels oud Nederlands spreekwoord van de bekende voetbalprofessor ons heeft geleerd. Het grote voordeel van centrale afhandeling van aanvragen is er voor zowel de aanvrager als de consument (wij dus). De aanvrager (een bedrijf of vereniging) hoeft nog maar op 1 plaats een aanvraag in te dienen en niet meer bij alle verenigingen separaat. De medisch specialist kan op 1 plaats zien of en door wie een activiteit is geaccrediteerd. De aanvrager kan in 1 keer aangeven door wie hij wenst dat de aanvraag geaccrediteerd wordt. Vanuit GAIA worden dan de aanvragen verspreid naar de betreffende commissies van de betreffende verenigingen. De commissie accreditatie van de wetenschappelijke vereniging blijft de inhoudelijke toetsing verrichten. De gevolgde nascholing van de individuele specialist wordt gearchiveerd in een centrale database. Hierin kan de individuele specialist in één oogopslag zien hoeveel accreditatiepunten/ uren hij/zij heeft verzameld en dus ook hoeveel er het lopende jaar nog verzameld moeten worden. Indien voldaan aan de voorwaarden kan dan via het systeem een aanvraag van herregistratie door zijn/haar wetenschappelijke vereniging in behandeling worden genomen. Dat klinkt tot zover goed. Wat zijn nu de haken en ogen die hiermee voor intensivisten kunnen gaan ontstaan? Deze zijn zowel van inhoudelijke als politieke aard. Zoals bekend is de NVIC geen wetenschappelijke vereniging omdat Intensive Care geen zelfstandig specialisme is. De aanvraag hiertoe is wel gedaan maar zal nog een lange weg gaan. Het directe effect hiervan is dat de NVIC niet betrokken is bij de ontwikkeling van het systeem, want is geen specialisme. Zowel voor accreditatie als herregistratie is er sprake van algemene en specifieke termen. Voor zover de termen van accreditatie en herregistratie centraal zijn vastgelegd betreft dit alléén algemene zaken, geen inhoudelijke. Iedere vereniging heeft hiervoor een eigen (specifiek) systeem. Voor de inhoudelijke kant van de beoordeling van accreditatie aanvragen is momenteel niet duidelijk welke vereniging de aanvragen betreffende Intensive Care gaat beoordelen. Het lijkt logisch dat de commissie accreditatie van

Agenda • 19th European Society of Intensive Care Medicine Congress: September 24th-27th. Barcelona, Spain. Information: www.esicm.org • ICAAC: September 27th-30th, San Francisco, USA. Information: www.icaac.org • Europaediatrics 2006 Conference: October 7th-10th , Barcelona, Spain. Information: www.kenes.com/europaediatrics/call.asp • Nationale Pijndagen 2006: October 11th-12th, Apeldoorn, the Netherlands. Information: www.nationalepijndagen.nl • CHEST 2006: 72nd Annual International Scientific Assembly of the American College of Chest Physicians: October 21th-26th, Salt Lake City, USA. Information: www.chestnet.org • Recent advances in medical gas therapy: October 28th, Amsterdam, The netherlands. Information: www.medical-gases.eu • Topics in IC: Multidisciplinair IC congres. November 1st, Lunteren, the Netherlands. Information: [email protected] • Najaarscongres NVA-NVT-NVIC: November 17th, Nieuwegein, the Netherlands. Information: www.nvic.nl • PAOG-cursus Urgentiegeneeskunde: November 24th, Amsterdam, the Netherlands. Information: www.cursusurgentiegeneeskunde.nl • NVIC Mechanische Beademingsdagen: November 30th and December 1st, Hotel en Congrescentrum De Reehorst, Ede, the Netherlands. Information: www.nvic.nl • NVIC Nederlandse Intensivistendagen 2007: January 31st- February 2nd, Hotel en Congrescentrum De Reehorst, Ede, the Netherlands. Information: www.nvic.nl • 3rd World Congress Abdominal Compartment Syndrome (WCACS 2007), March 22-24, 2007, Antwerp, Belgium. Information: www.wcacs.org • 12th International Symposium on Infections in the Critically ill Patient, June 8th-9th, 2007, Amsterdam, The Netherlands • NVIC Traumacongres 2007, June 14th – 15th, Hotel en Congrescentrum De Reehorst, Ede, the Netherlands. Information: www.nvic.nl • 5th World Congress of Pediatric Critical Care Societies: June 26-30 th 2007, Geneva Switzerland. Information: www.pcc2007.com • NVIC Circulatiedagen 2007: September 6th – 7th, Hotel en Congrescentrum De Reehorst, Ede, the Netherlands. Information: www.nvic.nl • NVIC Infectiecongres 2007: November 8th – 9th, Hotel en Congrescentrum De Reehorst, Ede, the Netherlands. Information: www.nvic.nl



513

16-08-2006 12:55:10


Commissies & Afgevaardigden Voedingscommissie Drs. R. Tepaske, AMC, Amsterdam (voorzitter) P. Bruynzeel, AMC, Amsterdam Drs. F.M.P. van Haren, VieCuri MC, Venlo Prof. Dr. E.M.H. Mathus-Vliegen, AMC, Amsterdam Dr. H.M. Oudemans-van Straaten, OLVG, Amsterdam Prof. Dr. D. Tibboel, Erasmus Medisch Centrum Sophia, Rotterdam Commissie IC transport Drs. E.J. van Lieshout, AMC, Amsterdam (voorzitter) Prof. Dr. J.J.L.M. Bierens, VUMC, Amsterdam Drs. R.J.R. Eijk, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. J.H.J. Meeder, Medisch Centrum Rijnmond Zuid, Rotterdam Drs. G.D. Vos, Academisch Ziekenhuis, Maastricht Drs. J. van de Wetering, Isala Klinieken, Zwolle Commissie Producttypering IC Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede (voorzitter) Dr. A.N. Roos, Catharina Ziekenhuis, Eindhoven Drs. A.M.G.A. de Smet, UMCU, Utrecht Drs. J.I. van der Spoel, OLVG, Amsterdam (secretaris) Dr. P.E. Spronk, Gelre Ziekenhuizen, Apeldoorn Drs. L.F. te Velde, Albert Schweitzer Ziekenhuis, Dordrecht Commissie Richtlijnontwikkeling Dr. J. Damen, Isala Klinieken, Zwolle (voorzitter) Drs. E.C. Boerma, Medisch Centrum, Leeuwarden Drs. E.A.C. Bouman, Academisch Ziekenhuis, Maastricht Dr. A.W.W.M. Koopman-van Gemert, Albert Schweitzer Ziekenhuis, Dordrecht Dr. H.J. van Leeuwen, UMCU, Utrecht (secretaris) Dr. K.H. Polderman, VUMC, Amsterdam Drs. A.M.T.J. Raben, Groene Hart Ziekenhuis, Gouda Dr. J.J. Spijkstra, VUMC, Amsterdam Drs. R. Tepaske, AMC, Amsterdam Drs. R.A.L. de Waal, Kennemer Gasthuis, Haarlem Wetenschapscommissie Prof. Dr. D. Tibboel, Erasmus Medisch Centrum Sophia, Rotterdam (voorzitter) Prof. Dr. L.P.H.J. Aarts, Universitair Medisch Centrum, Groningen Dr. D. Bergmans, Academisch Ziekenhuis, Maastricht Prof. Dr. Ir. C. Ince, AMC, Amsterdam Dr. J. Kesecioglu, UMCU, Utrecht Dr. R.P. Pickkers, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Dr. M.J. Schultz, AMC, Amsterdam Dr. P.E. Spronk, Gelre Ziekenhuizen, Apeldoorn Dr. J.E. Tulleken, Universitair Medisch Centrum, Groningen Commissie Internet Drs. C.P.C. de Jager, Jeroen Bosch Ziekenhuis, ‘sHertogenbosch (voorzitter) Dr. J. de Koning, Maxima Medisch Centrum, Veldhoven Drs. S. Kurban, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. F. Nooteboom, Viecuri Medisch Centrum, Venlo Dr. K.H. Polderman, VUMC, Amsterdam Drs. R.A.L. de Waal, Kennemer Gasthuis, Haarlem Vertegenwoordiging in de Gemeenschappelijk Intensive Care Commissie Prof. Dr. J.G. van der Hoeven, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. B.M. van der Kolk, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. A.M.G.A. de Smet, UMCU, Utrecht Commissie Kwaliteit Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede (voorzitter) Dr. M.S. Arbous, Leids Universitair Medisch Centrum, Leiden Dr. J. Damen, Isala Klinieken, Zwolle Prof. Dr. A.R.J. Girbes, VUMC, Amsterdam Drs. F.M. Versteegen, adviseur

514


Dr. P.H.J. van der Voort, Onze Lieve Vrouwe Gasthuis, Amsterdam Drs. R.A.L. de Waal, Kennemer Gasthuis, Haarlem Dr. A.J. Woittiez, Twenteborg Ziekenhuis, Almelo Commissie Fellows Drs. I. Stijn, Onze Lieve Vrouwe Gasthuis, Amsterdam (voorzitter) Drs. N. van Bussink-van Dijk, Academisch Ziekenhuis Maastricht Dr. H. Buter, Universitair Medisch Centrum, Groningen Drs. J.A.R. van Dijk, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. M.I. Fokkema, Universitair Medisch Centrum, Groningen Drs. M.G.E.C. Hilkens, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. B. Kors, VU Medisch Centrum, Amsterdam Drs. C. Kleppe, VU Medisch Centrum, Amsterdam Dr. H.G. Kreeftenberg, UMCU, Utrecht Drs. D.J. Mehagnoul, Academisch Ziekenhuis Maastricht Drs. A.J. Paling, Leids Universitair Medisch Centrum, Leiden Drs. M. van Spreuwel-Verheijen, OLVG, Amsterdam Commissie Kwaliteitsindicatoren IC Dr. P.H.J. van der Voort, Onze Lieve Vrouwe Gasthuis, Amsterdam (voorzitter) Drs. D.H.C. Burger, St. Elisabeth Ziekenhuis, Tilburg Drs. A.A. Corsten, Canissius-Wilhelmina Ziekenhuis, Nijmegen Drs. F.E. van Dijk, Antonius Ziekenhuis, Nieuwegein (NVICV) Mw. M. Fuijkschot, Ziekenhuis Rivierenland Tiel Dr. W.C. Graafmans, RIVM, Utrecht Dr. E. de Jonge, AMC, Amsterdam Drs. M. de Vos, RIVM, Utrecht Mevr. J. Vreman, Radboud Universiteit Nijmegen Medisch Centrum , Nijmegen Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede Commissie Nefrologie Dr. H.M. Oudemans-van Straaten, OLVG, Amsterdam (voorzitter) Drs. C.S.C. Bouman, AMC, Amsterdam Prof. Dr. A.B.J. Groeneveld, VUMC, Amsterdam Dr. A.C.J.M. de Pont, AMC, Amsterdam Prof. Dr. M.R.C. Schetz, Universiteitsziekenhuis, Leuven Dr. A.J. Woittiez, Twenteborg Ziekenhuis, Almelo Commissie Complicatieregistratie Dr. M.S. Arbous, Leids Universitair Medisch Centrum, Leiden (voorzitter) Dr. A. Balzereit, Leids Universitair Medisch Centrum, Leiden Dr. B. Beishuizen, VU Medisch Centrum, Amsterdam Drs. L. Dawson, Reinier de Graafgasthuis, Delft Drs. S. Dijkstra, Groene Hart Ziekenhuis, Gouda Prof. Dr. J.G. van der Hoeven, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. A. Manten, Meander Medisch Centrum, Amersfoort

Commissie Zorgvernieuwingsprojecten Dr. A.J.J. Woittiez, Twenteborg Ziekenhuis, Almelo (voorzitter) Drs. M. van Berkel, Beatrix Ziekenhuis, Gorinchem Dhr P. Bocxe, AMC, Amsterdam Mw. H. van Dijk, Reinier de Graaf Gasthuis, Delft Dhr A. Klijnstra, Ziekenhuis Tjongerschans, Heerenveen Mw. Drs. L.M.T. Schouten, Senior adviseur kwaliteitsinstituut voor de gezondheidszorg CBO Drs. F. van Tilborg, Reinier de Graaf Gasthuis, Delft Dhr. H. Verhey, Twenteborg Ziekenhuis, Almelo (secretaris) Commissie Accreditatie Drs. R.A.L. de Waal, Kennemer Gasthuis, Haarlem (voorzitter) Prof. Dr. A.R.J. Girbes, VUMC, Amsterdam Drs. A. Manten, Meander Medisch Centrum, Amersfoort Drs. I.A. Meynaar, Reinier de Graaf Gasthuis, Delft Drs. H.H. Ponssen, Albert Schweitzer Ziekenhuis, Dordrecht Drs. D.H.T. Tjan. Ziekenhuis Gelderse Vallei, Ede Dr. D.F. Zandstra, OLVG, Amsterdam Programmacommissie 2007 Prof. Dr. J.G. van der Hoeven, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen (voorzitter) Dr. S.J.A. Aerdts, Isala Klinieken, Zwolle Prof. Dr. A.R.J. Girbes, VUMC, Amsterdam Prof. Dr. G.J. Scheffer, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Prof. Dr. D. Tibboel, Erasmus Medisch Centrum Sophia, Rotterdam Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede Bestuurscommissie FCCS Nederland Drs. F. Nooteboom, VieCuri MC, Venlo (voorzitter) Drs. B.M. van der Kolk, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. L.M. Lambalk, Westfries Gasthuis, Hoorn Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede FCCS Course Directors Drs. F. Nooteboom, VieCuri MC, Venlo (National Course Director) Drs. D.H.C. Burger, St. Elisabeth Ziekenhuis, Tilburg Dr. N.A. Foudraine, VieCuri MC, Venlo Drs. H.P.M.M. Gelissen, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Prof. Dr. J.G. van der Hoeven, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. E.F. Salm, Reinier de Graaf Gasthuis, Delft Drs. J.M.M. Verwiel, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede Prof. Dr. J.H. Zwaveling, Academisch Ziekenhuis, Maastricht

Commissie Ethiek Dr. R.Th. Gerritsen, Medisch Centrum, Leeuwarden (voorzitter) Dr. R.G. Hoff, UMCU, Utrecht Dr. B.S. Hylkema, Medisch Spectrum Twente, Enschede Dr. E.J.O. Kompanje, Erasmus Medisch Centrum, Rotterdam Mr. E.W.M. Meulemans, advocaat, Zwolle Dr. B.W. Mooi, Isala Klinieken, Zwolle Prof. Dr.J. Kesecioglu, Universitair Medisch Centrum Utrecht

Commissie NVIC Medium Care Drs. D.H.T. Tjan, Ziekenhuis Gelderse Vallei, Ede (voorzitter) Drs. L.E.M. Haas, Ziekenhuis Gelderse Vallei, Ede Drs. M.S. van der Steen, Kennemer Gasthuis, Haarlem Dr. J.J. Spijkstra, VU Medisch Centrum, Amsterdam Dr. M.A. Boermeester, Academisch Medisch Centrum, Amsterdam Drs. E.F. Salm, Reinier de Graaf Gasthuis, Delft Dr. J.J. van Lieshout, Academisch Medisch Centrum, Amsterdam Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede Prof. Dr. J. Bakker, Erasmus MC locatie Dijkzigt

Nationale Visitatiecommissie IC Prof. Dr. A.R.J. Girbes, VUMC, Amsterdam (voorzitter) Drs. S.J. van Leeuwen, St. Jans-Gasthuis, Weert C. Tielemans, Amphia Ziekenhuis, Breda (NVICV) Drs. F.M. Versteegen, adviseur

Werkgroep Neuro-Intensive Care Neurologen Dr. G.W. van Dijk, Canisius Wilhelmina Ziekenhuis Dr. M. van der Jagt, Erasmus MC R’dam Dr. R.W.M. Keunen, Hagaziekenhuis Den Haag

Dr. R.A. van der Kruijk, Slingeland Doetinchem Dr. P.E. Vos, UMCN Nijmegen Intensivisten Dr. M.A. Kuiper, Medisch Centrum Leeuwarden (voorzitter) Dr. S.J.A. Aerdts, Isala klinieken locatie Sophia Zwolle Dr. D. Hasan, VieCuri Venlo Dr. C. Hoedemaekers, Universitair Medisch Centrum St Radboud Dr. J. Horn, Academisch Medisch Centrum Amsterdam Drs. J.J. Maas, Leids Universitair Medisch Centrum Dr. J. van der Naalt, Utrecht Medisch Centrum Groningen Dr. K.H. Polderman, VUMC Amsterdam Dr. A.J.C. Slooter, Universitair Medisch Centrum Utrecht Drs. J.C.W. Taal, Leids Universitair Medisch Centrum Drs. W.J. Thijsse, Erasmus MC R’dam Neurochirurgen Dr. A.I.R. Maas, Erasmus MC Dr. S.M. Peerdeman, VU Medisch Centrum Amsterdam Dr. B. Verweij, Universitair Medisch Centrum Utrecht

Afgevaardigden Stuurgroep IC Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede Nederlandse Reanimatieraad Drs. M.J. Gardien, Erasmus MC, Rotterdam Hemovigilantie Project TRIP Dr. A.W.M.M. Koopman-van Gemert, Albert Schweitzer Ziekenhuis, Dordrecht SWAB Richtlijn Gist- en Schimmelinfecties Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede CBO Richtlijn perioperatieve Voeding Drs. R. Tepaske, AMC, Amsterdam Liaison officer NIV richtlijn commissie Drs. E.J. van Lieshout, AMC, Amsterdam CBO Richtlijn cystic fibrosis Drs. P.M.S. Schröder, Ziekenhuis, Blaricum. EBRO richtlijn AAA Drs. J.C. Pompe, Radboud Universiteit Nijmegen Medisch Centrum, Nijmegen ESICM Cobatrice Prof. Dr. A.R.J. Girbes, VUMC, Amsterdam Drs. A.R.H. van Zanten, Ziekenhuis Gelderse Vallei, Ede Werkgroep Infectie Preventie (herzien richtlijn Intravasale Therapie) Drs. C.V. Elzo Kraemer, Leids Universitair Medisch Centrum, Leiden Werkgroep Preventie van perioperatieve cardiale complicaties bij niet-cardiale chirurgie Dr. H.J. van Leeuwen, Ziekenhuis Gelderse Vallei, Ede Externe Klankbordgroep Cardiochirurgische Zorgketen Dr. P.H.J. van der Voort, Onze Lieve Vrouwe Gasthuis, Amsterdam Genosept, ESICM DR. J.A. Hazelzet, Erasmus Medisch Centrum, Rotterdam Werkgroep Richtlijnontwikkeling Sedatie en/of analgesie door niet-anesthesiologen Dr. J.J. Spijkstra, VU Medisch Centrum, Amsterdam


16-08-2006 12:55:11


de NVIC dit zal blijven doen, maar dat staat niet op voorhand vast. Vooralsnog zijn intensivisten hierin afhankelijk van de opstelling van hun moedervereniging. Ook voor de herregistratie is de situatie voor intensivisten niet duidelijk. De termen voor herregistratie van intensivisten worden niet bepaald door de NVIC, niet op dit moment , en getuige het voorstel van de GIC wat nog in conceptfase is (zie website NVIC www.nvic.nl) ook niet in de nabije toekomst. Via de GIC heeft een delegatie van de NVIC hierop wel invloed maar de termen voor herregistratie worden door de moederverenigingen bepaald. Dit betreft zowel de algemene (hoeveel uren, welke procedure van herregistratie en van beroep tegen een beslissing) als de specifieke inhoudelijke termen (wat zijn IC gerelateerde werkzaamheden, wat zijn IC specifieke diagnostische en therapeutische procedures en interventies, moeten alle intensivisten voldoen aan dezelfde termen ongeacht het niveau waarop zij werken?). De grote vraag in dit alles is welke positie dient de NVIC in te gaan nemen. De Intensive Care Geneeskunde heeft zich de afgelopen 30

551 intensivisten en fellows 2 rustende leden 1030 overige leden 43 overige abonnees Totaal 1 juni 2006: 1584 Totaal 1 augustus 2006: 1626 Totaal lezersbereik: 3758

jaar stormachtig ontwikkeld. Pas de laatste jaren krijgt de beroepsgroep vat op de organisatorische en inhoudelijke aspecten van de Intensive Care Geneeskunde en de beoefenaren daarvan. Politiek gezien is de storm nog niet overgewaaid en is er nog (virtuele?) tegenwind. In deze situatie is het van belang dat zowel de termen van accreditatie als de termen voor herregistratie van intensivisten goed worden vastgelegd. De centrale vraag hierin is “wie gaat dat bepalen?”. Het is van groot belang dat deze belangrijke discussie in de beroepsgroep gaat plaatsvinden waarbij wij als NVIC ons goed moeten realiseren dat er meerdere spelers op het veld zijn. Ruud A.L. de Waal, intensivist [email protected]

Literatuur Waal de, RAL, Damen J, Onvoldoende nacholing kan effect hebben op herregistratie, Neth J Crit Care, 2006, 1; 32

NVIC Bestuur Dr. K.H. Polderman Internist-intensivist VU Medisch Centrum, Amsterdam Voorzitter a.i. E-mail: [email protected] Drs. B.M. van der Kolk Chirurg-intensivist Universitair Medisch Centrum St. Radboud, Nijmegen Penningmeester E-mail: [email protected] Drs. J.H.J. Meeder Anesthesioloog-intensivist Medisch Centrum Rijnmond-Zuid, Rotterdam Secretaris E-mail: [email protected]

Verenigingen die accreditatie verlenen aan NVIC activiteiten in 2006 NVIC Nederlandse Intensivistendagen 2007 Woensdag 1, donderdag 2 en vrijdag 3 februari 2006 Hotel en Congrescentrum De Reehorst, Ede NVIC Congres: Neurologische Problematiek op De Intensive Care Donderdag 8 en vrijdag 9 juni 2006 Hotel en Congrescentrum De Reehorst, Ede NVIC Mechanische Beademingsdagen 2006 Donderdag 30 november en vrijdag 1 december

Drs. I. van Stijn Internist-intensivist i.o. Onze Lieve Vrouwe Gasthuis, Amsterdam Bestuurslid E-mail: [email protected]

Prof. Dr. D. Tibboel Kinderarts-intensivist Erasmus MC Sophia Kinder ziekenhuis, Rotterdam Bestuurslid E-mail: [email protected]

Drs. C.P.C. de Jager Internist-intensivist Jeroen Bosch Ziekenhuis, Den Bosch Bestuurslid E-mail: [email protected]

Secretariaat NVIC: Stationsweg 73 C, 6711 PL Ede. Telefoon: 0318-693337, Fax: 0318-693338, E-mail: [email protected]

Drs. A.M.G.A. de Smet Anesthesioloog-intensivist Universitair Medisch Centrum, Utrecht E-mail: [email protected]

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16-08-2006 12:55:12

advertentie NJCC

16-08-2006

13:28

Pagina 1

advert

nvic a

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2007 Procedure voor het indienen van • proefschriften voor Pfizer NVIC Award 2007 • abstracts • case reports Pfizer NVIC Award 2007

bestaan uit een certificaat en een geldbedrag. De totale tijd voor de mondelinge presentaties bedraagt 12 minuten inclusief vragen. Voor presentatie geselecteerde inzendingen worden niet als poster tentoongesteld. Het formaat van de posters is maximaal 120 cm (horizontaal) x 90 cm (verticaal). Tijdens de lunchpauze bestaat de mogelijkheid de poster te presenteren aan de jury. De posters zullen in principe gedurende de gehele periode van de Intensivistendagen 2007 ten toon gesteld blijven.

NVIC case reports

Op de derde dag van de Nederlandse Intensivistendagen, op 2 februari 2007, bestaat er de mogelijkheid voor fellows hun genomineerde case report te presenteren aan een vakkundige jury, welke de case reports beoordeeld. Van de ingezonden case reports worden er vijf genomineerd om een presentatie te houden van 20 minuten, inclusief het stellen en beantwoorden van vragen. Het beste case report wordt beloond met een prijs en een certificaat.

Instructies voor het insturen van Pfizer NVIC Award nominaties 2007

De Nederlandse Vereniging voor Intensive Care heeft in de periode 1999–2006 61 proefschriften ontvangen die genomineerd zijn voor de Pfizer NVIC Award. Een deskundige jury beoordeelt de thesen. Tijdens de Nederlandse Intensivistendagen, gehouden van 31 januari tot en met 2 februari 2007, houden de genomineerden een korte voordracht over hun werk. De Award jury maakt vervolgens de winnaar bekend. Deze jury staat onder leiding van Prof. Dr. D. Tibboel, voorzitter van de wetenschapscommissie van de NVIC. De leden van deze commissie zullen de winnaar aanwijzen op basis van vooraf gestelde criteria.

In aanmerking komen proefschriften uit 2006 die relevant zijn voor Intensive Care geneeskunde. Om in aanmerking te komen dient u vóór 1 oktober 2006 11 exemplaren van uw proefschrift te zenden aan het NVIC secretariaat (adres: zie onder). Als genomineerde dient u zich in te schrijven voor de Wetenschapsdag op 1 februari 2007 of het gehele congres. Bovendien houdt u als genomineerde een korte voordracht waarin de belangrijkste aspecten en bevindingen van uw proefschrift worden belicht. U ontvangt voor 10 oktober 2006 een ontvangstbevestiging. Indien u op 10 oktober 2006 nog geen bevestiging hebt ontvangen dient u zelf direct contact op te nemen met het NVIC secretariaat

Prijs voor het beste proefschrift

Instructies voor het insturen van abstracts

De prijs bestaat uit een geldbedrag voor de aankoop van 150 exemplaren van het proefschrift. Deze proefschriften zullen gratis toegestuurd worden aan alle IC afdelingen in Nederland. Op deze wijze wordt de nieuw opgedane kennis zoveel mogelijk verspreid.

NVIC poster en abstract Awards

De Nederlandse Intensivistendagen 2007 zijn wederom uitgebreid met een wetenschapsdag op 1 februari 2007. Dé gelegenheid om het vele originele Nederlandse wetenschappelijk werk aan de orde te laten komen. Dien een abstract in van uw eigen originele werk, of stimuleer de jonge leden van uw onderzoeksgroep om de (voorlopige) resultaten van hun werk op deze dag te komen presenteren. Ingediende abstracts worden beoordeeld door de NVIC poster & abstractcommissie. Het abstract kan ofwel worden geaccepteerd voor mondelinge presentatie (maximaal 20 abstracts), of als poster. In totaal zullen de 5 beste abstracts en/of posters worden beloond met een prijs. De vijf prijzen

Informatie voor auteurs • De NVIC legt zich erop toe dat de kwaliteit van de abstracts en presentaties optimaal is. Het is immers een afspiegeling van de kwaliteit van het werk van haar leden en gasten. Om de kans op het afwijzen van abstracts te verkleinen is het essentieel het abstract volgens onderstaande aanwijzingen te vervaardigen. De abstracts worden geblindeerd beoordeeld (de namen van de auteurs zijn niet bekend bij de reviewers). • De abstracts worden gepubliceerd in het NJCC. Er bestaat een sterke voorkeur voor ‘nieuw materiaal’, dat wil zeggen data die niet eerder gepubliceerd zijn. • Met het toezenden van een abstract doen de auteurs een toezegging om bij acceptatie de data te presenteren op 1 februari 2007. Dit kan zowel voor mondelinge presentatie als voor posterpresentatie zijn. De presenterend auteur van het abstract moet zich inschrijven voor de NVIC Intensivistendagen. De auteurs moeten aangeven onder welke categorie hun abstract valt.

de uiterste inzendingtermijn is 1 oktober 2006

de n e derlan dse i ntensivisten dagen worden gehou den van 31 januari tot en met 2 februari 2007 NVIC secretariaat


• Stationsweg 73C, 6711 PL Ede • Telefoon: 0318 - 69 33 37 • Fax: 0318 - 69 33 38 • E-mail: [email protected] • www.nvic.nl

16-08-2006 13:31:31

advertentie NJCC

16-08-2006

13:28

Pagina 2

Categorieën: • Case reports • Sepsis and Inflammation • Pediatrics • Neurology • Circulation and Hemodynamics • Respiration and Ventilation • Anesthesiology • Nephrology • Quality and Organisation Abstract titel De titel is kort en specifiek, zonder afkortingen, en geeft de aard van het onderzoek weer. Een dynamische en conclusieve titel heeft de voorkeur boven een beschrijvende titel. Auteursnamen De insturend auteur wordt aangewezen als de presenterend auteur. Abstract data Alle abstracts worden Engelstalig ingestuurd, in lettertype ‘Arial’. De lengte van de abstracts is maximaal 500 woorden (10 pitch, justified, regelafstand 1.5). Indien het abstract tabellen bevat dient het abstract met 50 woorden per tabel te worden verminderd. Data dienen niet verdeeld te worden over verschillende abstracts. Abstract tekst • De structuur van het abstract (Introductie, Vraagstelling/ Hypothese, Methode, Resultaten, Conclusie) moet duidelijk herkenbaar zijn. • Beschrijf kort het onderwerp en de vraagstelling van de studie. • Beschrijf de methoden voldoende adequaat zodat de toepasbaarheid toetsbaar is. Bij dierexperimenteel onderzoek dient het soort, stam, sexe en gewicht te worden vermeld. Gebruik generieke stofnamen. Noem de grootte van de studiegroepen. • Beschrijf de resultaten in voldoende detail om de conclusie te waarborgen. Maak zoveel mogelijk gebruik van kwantitatieve data. Alleen vermelding van een stijging of daling met een p-waarde is onvoldoende. Een opmerking als ‘de resultaten zullen op het congres worden gepresenteerd’ is niet acceptabel. • Standaardafkortingen mogen zonder uitleg worden gebruikt. • Niet-standaard afkortingen moeten tussen haakjes worden uitgeschreven en het gebruik hiervan moet tot een minimum worden beperkt. • Gebruik maximaal 2 referenties. Vermelding van acknowledgements en financiële support o.b.v. een beurs is niet toegestaan.

Veelvoorkomende tekortkomingen • De vraagstelling/ hypothese wordt niet genoemd. Advies: eindig de Introduction met ‘Aim of present study is to…’ of ‘We assessed the hypothesis that…’ • De conclusie wordt niet genoemd. Advies: eindig met ‘In conclusion,...’ • De grootte van de studiepopulatie wordt niet genoemd. Zonder ‘sample size’ zijn gemiddelde waarden ± sem zonder waarde. • Overmatig gebruik van afkortingen vermindert de leesbaarheid van het abstract. Gebruik niet meer dan 3 nietstandaard afkortingen. • Typfouten irriteren de meeste reviewers en lezers. • Maak gebruik van maximaal 2 referenties. • Geef de relevantie van de studie aan. • Houd grafieken/ tabellen simpel. Zorg dat de tekst ervan leesbaar is. • Laat het abstract van tevoren aan je collega’s zien, en maak gebruik van hun suggesties. Indienen van de abstracts De abstracts kunnen uitsluitend worden ingediend per e-mail naar het volgende adres: [email protected]. Bij het inzenden van een abstract dient u een formulier in te vullen met gegevens van de auteurs en het inzendend instituut. Dit formulier kunt u vinden op de NVIC website. Wanneer u een abstract instuurt dient u zich in te schrijven voor de Wetenschapsdag op 1 februari 2007 of voor het gehele congres. De deadline voor het indienen van de abstracts is 1 oktober 2006. U ontvangt voor 10 oktober 2006 een ontvangstbevestiging. Indien u op 10 oktober 2006 nog geen bevestiging hebt ontvangen dient u zelf direct contact op te nemen met het NVIC secretariaat.

Instructies voor het insturen van case reports

De case reports kunnen uitsluitend door fellows per e-mail worden ingediend, [email protected], onder vermelding van case reports Nederlandse Intensivistendagen 2007. Bij het inzenden van een case report dient u een formulier in te vullen met gegevens van de auteurs en het inzendend instituut. Dit formulier kunt u vinden op de NVIC website. Wanneer u een case report instuurt dient u zich in te schrijven voor vrijdag 1 ferbuari 2007 of voor het gehele congres De deadline voor het indienen van de case reports is 1 oktober 2006. U ontvangt voor 10 oktober 2006 een ontvangstbevestiging. Indien u op 10 oktober 2006 nog geen bevestiging hebt ontvangen dient u zelf direct contact op te nemen met het NVIC secretariaat.

de uiterste inzendingtermijn is 1 oktober 2006

de n e derlan dse i ntensivisten dagen worden gehou den van 31 januari tot en met 2 februari 2007 NVIC secretariaat


• Stationsweg 73C, 6711 PL Ede • Telefoon: 0318 - 69 33 37 • Fax: 0318 - 69 33 38 • E-mail: [email protected] • www.nvic.nl

16-08-2006 13:32:30

algemen e i n for mati e

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16-08-2006 13:32:33

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2 0 0 6

Nederlandse Vereniging voor Intensive Care (NVIC)

me c h a n i s c h e bea d e mi n g s dag e n 200 6 donderdag 30 november 2006 vrijdag 1 december 2006 hotel en congrescentrum de reehorst, ede


16-08-2006 13:32:34

38


n v i c


m e c h a n i s c h e b eademi ngsdagen 2006

2 0 0 6

Hotel en Congrescentrum De Reehorst, Ede

programma

dag 1 d o n derdag 30 november 2006 08.30 uur

Ontvangst en inschrijving

13.45 uur

Workshop

14.15 uur

Workshop

Voorzitters:

JG van der Hoeven ARH van Zanten

Voorzitters:

B van den Berg A Manten

9.30 uur

Mechanische beademing: gevolgen van mechanische beademing JG van der Hoeven

14.45 uur

Luchtwegmanagement: bezint eer ge begint DHT Tjan

9.55 uur

Klassieke beademingsmodaliteiten: voor- en nadelen ARH van Zanten

15.10 uur

Pauze

15.40 uur

De percutane tracheotomie H Delwig

16.05 uur

Non-invasieve beademing JMM Verwiel

16.30 uur

Casusbespreking: Een patiënt met een ernstige status astmaticus JG van der Hoeven

10.20 uur

Nieuwe beademingsvormen: algemene aspecten JG van der Hoeven

10.45 uur

Geassisteerde beademing en longmechanica B van den Berg

11.10 uur

Pauze

11.45 uur

Workshop

17.15 uur

Borrel

12.15 uur

Workshop

18.00 uur

Diner

12.45 uur

Lunch

20.00 uur Algemene Ledenvergadering

w o r ks h o p 1

workshop 3

w o r ks h o p 2

workshop 4

Servo I DHT Tjan / ARH van Zanten Tijdens deze workshop worden enkele algemene aspecten van mechanische beademing uitgelegd. Volume- en druk, constante beademing en de consequenties hiervan zullen op het scherm inzichtelijk gemaakt worden. Veel aandacht wordt besteed aan het vaststellen en meten van PEEPi. Evita XL A Manten Deze workshop zal met name gericht zijn op de 2 bijzondere beademingsvormen die op deze machine mogelijk zijn: APRV en PPS.


Gallileo DA Dongelmans Deze workshop richt zich volledig op het inzichtelijk maken van adaptive support ventilation (ASV).

Percutane Tracheotomie H Delwig Tijdens deze workshop oefent u zelf het uitvoeren van de verschillende technieken.

16-08-2006 13:32:35


n v i c


39

2 0 0 6

m e c h a n i s c h e beademi ngsdagen 2006 Hotel en Congrescentrum De Reehorst, Ede

programma

dag 2 vrijdag 1 d e c e m b e r 2006 9.00 uur

Workshop

14.00 uur

Workshop

9.30 uur

Workshop

14.30 uur

Workshop

Voorzitters:

MJM Bonten JE Tulleken

Voorzitters:

JG van der Hoeven ARH van Zanten

10.00 uur

Pathofysiologie van ARDS: consequenties voor de behandeling ABJ Groeneveld

15.00 uur

Algemene beoordeling van de thoraxfoto op de Intensive Care RFE Wolf

10.25 uur

Mechanische beademing bij ARDS: recente inzichten bij mechanische beademing ARH van Zanten

15.25 uur

Pauze

15.55 uur

Beademing geassocieerde pneumonie: preventie en diagnostiek JE Tulleken

16.20 uur

Beademing geassocieerde pneumonie: therapie MJM Bonten

16.45 uur

Einde programma

10.50 uur

Ontwennen van mechanische beademing B van den Berg

11.15 uur

Pauze

11.45 uur

Kinetische therapie en buikligging ARH van Zanten

12.10 uur

Recruitment manoeuvres: hoe en wanneer? JG van der Hoeven

12.35 uur

Hoog frequente beademing: klinische resultaten AJ van Vught

13.00 uur

Lunch

w o r ksh o p 5

workshop 7

w o r ksh o p 6

workshop 8

Non-invasieve beademing JMM Verwiel Met behulp van een specifiek hiervoor ontworpen beademingsapparaat oefent u het instellen en vergelijkt u dit met een standaard beademingsmachine.

Capnografie B van den Berg Tijdens deze workshop leert u de praktische aspecten van capnografie. Aandacht zal vooral gericht zijn op het detecteren van acute noodsituaties.


Buikligging / Kinetische therapie HJA Hensing Tijdens deze workshop krijgt u meerdere mogelijkheden van buikligging gedemonstreerd. Hierbij wordt veel aandacht geschonken aan verschillen in beschikbare matrassen en bedden.

Bronchoscopie PMS Schröder / LMA Heunks Tijdens deze workshop kunt u met de bronchoscoop oefenen op een model van de luchtwegen. Aandacht zal worden geschonken aan het opheffen van atelectase en het verrichten van een BAL.

16-08-2006 13:32:35

sp rek e r s e n vo o r z i t t e r s 3 0 n ove mbe r 1 dece mbe r 2006


n v i c


41

2 0 0 6

Dr B van den Berg Internist-intensivist Erasmus MC Dijkzigt, Rotterdam

Prof Dr ABJ Groeneveld Internist-intensivist VU Medisch Centrum, Amsterdam

Drs A Manten Internist-intensivist Meander Medisch Centrum, Amersfoort

Drs JMM Verwiel Internist-intensivist Radboud Universiteit Nijmegen Medisch Centrum

Dr MJM Bonten Internist-infectioloog Universitair Medisch Centrum, Utrecht

Drs HJA Hensing Beademingsverpleegkundige Leids Universitair Medisch Centrum, Leiden

Drs PMS Schröder Longarts-intensivist Ziekenhuis Gooi-Noord, Blaricum

Prof Dr AJ van Vught Kinderarts-intensivist Wilhelmina Kinderziekenhuis, Utrecht

Drs H Delwig Internist-intensivist Universitair Medisch Centrum, Groningen

Dr LMA Heunks Longarts i.o. Radboud Universiteit Nijmegen Medisch Centrum

Drs DHT Tjan Anesthesioloog-intensivist Ziekenhuis Gelderse Vallei, Ede

Dr RFE Wolf Radioloog Universitair Medisch Centrum, Groningen

Drs DA Dongelmans Anesthesioloog-intensivist Academisch Medisch Centrum, Amsterdam

Prof Dr JG van der Hoeven Internist-intensivist Radboud Universiteit Nijmegen Medisch Centrum

Dr JE Tulleken Internist-intensivist Universitair Medisch Centrum, Groningen

Drs ARH van Zanten Internist-intensivist Ziekenhuis Gelderse Vallei, Ede

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• NVIC Nederlandse Intensivistendagen 2007

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16-08-2006 13:38:42

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< € 95,- < € 15,50 < € 25,- < € 19,50 < € 29,50

< € 95,< € 15,50 < € 25,< € 19,50 < € 29,50

Fundamental Critical Care Support Course (FCCS) Congreshotel 'De Werelt', Lunteren < € 495 woensdag en donderdag 17 en 18 januari 2007 < € 495 dinsdag en woensdag 13 en 14 februari 2007 < € 495 dinsdag en woensdag 6 en 7 maart 2007 < € 495 donderdag en vrjidag 12 en 13 april 2007 < € 495 woensdag en donderdag 18 april en 19 april 2007 < € 495 donderdag en vrijdag 10 mei en 11 mei 2007 < € 495 donderdag en vrijdag 31 mei en 1 juni 2007 < € 495 donderdag en vrijdag 13 en 14 september 2007 < € 495 donderdag en vrijdag 27 en 28 september 2007 < € 495 dinsdag en woensdag 9 en 10 oktober 2007 < € 495 woensdag en donderdag 14 en 15 november 2007 < € 495 donderdag en vrijdag 13 en 14 december 2007 < Ik wil instructeur worden bij de FCCS-cursussen en zal de eerste keer als hybride meedoen, neem contact met mij op. NVIC Mechanische Beademingsdagen 2006 Hotel en Congrescentrum De Reehorst, Ede Donderdag 30 november en vrijdag 1 december 2006 - Toeslag logies en ontbijt (éénpersoonskamer) - Treinkaartje dagretour 2e klas Reehorst Ede* - Treinkaartje dagretour 1e klas Reehorst Ede* - Treinkaartje meerdaags retour 2e klas Reehorst Ede* - Treinkaartje meerdaags retour 1e klas Reehorst Ede*

kwa l it e itsvi s itati e < Graag ontvang ik een informatiepakket om een kwaliteitsvisitatie op mijn Intensive Care afdeling aan te vragen. De kosten van een visitatie bedragen € 3950 < Ik wil visiteur worden bij de Nationale Visitatiecommissie en ontvang hierover graag informatie. l i d ma ats c h a p Ik word alleen lid van NVIC en ik betaal: Intensivist-leden en fellows: Buitengewone leden: readers, symposiumboeken en cd-rom’s ik bestel de volgende artikelen: Plaats (bij deelname aan cursussen en symposia is het cursusmateriaal inbegrepen) < NVIC Nederlandse Intensivisten Dagen 2002 Arnhem < NVIC Circulatiecursus 2003 Arnhem < NVIC Nederlandse Intensivisten Dagen 2004 Arnhem < NVIC Mechanische Beademingsdagen 2004 Arnhem < NVIC Circulatiecursus 2004 Arnhem < NVIC Nederlandse Intensivistendagen 2005 Ede < NVIC NEMO-cursus Ede < NVIC Circulatiedagen 2005 Ede < NVIC Nederlandse Intensivistendagen 2006 Ede < NVIC Neuro-congres Ede < ik bestel geen readers De prijs is inclusief verzendkosten. Handtekening

< € 165 (contributie 2006) < € 110 (contributie 2006) Datum

ISBN-nummer

Prijs

07/08-02-2002 20 /21-11-2003 10/11/12-03-2004 10/11-06-2004 16 /17-09-2004 23/24/25-02-2005 9/10-06-2005 10/11/2005 1/2/3-02-2006 8/9-06-2006

90-75523-33-5 90-75523-41-6 90-75523-45-9 90-75523-44-0 90-75523-46-7 90-75523-48-3 90-75523-50-5 90-75523-49-1 90-75523-69-6 90-75523-61-0

€ € € € € € € € € €

Aantal

22,50 15,00 22,50 15,00 15,00 22,50 15,00 15,00 22,50 15,00

Naam ondergetekende Datum Plaats

(niet ondertekende of onvolledig ingevulde registratieformulieren kunnen niet in behandeling genomen worden) machtiging Overeenkomstig de bekende algemene inschrijvings- en betalingsvoorwaarden van de nvic verklaar ik dat de nvic gemachtigd is om van eerdergenoemd bank- of girorekeningnummer de bedragen af te schrijven die samenhangen met: < deelname aan de aangegeven congressen, cursus(sen) en/of symposia < lidmaatschap van de nvic < bestelling van reader(s) en/of symposiumboeken Handtekening

Naam ondergetekende Datum Plaats

(bij machtiging dient u dus tweemaal uw handtekening te plaatsen. Buitenlandse incasso is niet mogelijk.) d it r e g i st r at i e formu li e r i n e e n e nve lop gratis te rugstu re n naar: nvic, antwoordnumme r 2459, 6710 wb e de (gld)


16-08-2006 13:32:38

adv 210x277

15-05-2006

13:58

Pagina 1

06.tyg.6.8 Productinformatie zie elders in dit blad.

Een nieuw antibioticum doet de ronde


Leading the way to a healthier world

16-08-2006 13:59:00

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16-08-2006 13:58:57

Netherlands Journal. I.A. Meynaar, P.L. Tangkau, B.C. Verdouw, M. Wagemans, L. Dawson, E.F.Salm, F. Borst

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