NJCC Volume 10, Augustus 2006

Transcription

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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10
16-08-2006 13:58:58
adv 21
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
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
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
•What are the consequences of peepi during spontaneous and controlled 487
•
Interactie, Ede
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v i l l a y, The Hague
Layout
Unit-1, The Hague
Printing
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Business contacts
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Zijlweg 12
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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:
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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507
507
511
473
16-08-2006 12:23:40
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VU folder workshop.indd 1
10-08-2006 10:22:10
16-08-2006 12:23:42
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
Gelderse Vallei Hospital
PO box 9025
6710 HN Ede
Kees Polderman, Internet Editor/ Section Editor
Neuro
PO box 7057
1007 MB Amsterdam
Jan Bakker, Section Editor
Hemodynamics
Erasmus Medical Center Rotterdam
PO Box 2040
3000 CA Rotterdam
Armand Girbes, Section Editor
General
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;
PO Box 2060
3000 CB Rotterdam
Paul van den Berg
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
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
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
Medical Center Leeuwarden
PO Box 888
8901 BR Leeuwarden
Peter van der Voort, Correspondence Editor
Medical Center Leeuwarden
PO Box 888
8901 BR Leeuwarden
Evert de Jonge, Section Editor
Scoring and quality assessment
Mail stop G3-206
Meibergdreef 9
1105 AZ Amsterdam
Heleen Oudemans-van Straaten,
Section Editor
Nephrology
Onze Lieve Vrouwe Gasthuis
PO Box 95500
1090 HM Amsterdam
Peter Pickkers, Section Editor
Sepsis and inflammation
UMC St. Radboud
PO Box 9101
6500 HB Nijmegen
Dick Tibboel, Section Editor
Pediatrics
Pediatric Intensive Care Unit;
Sophia Children’s Hospital;
PO Box 2060
3000 CB Rotterdam
Andrew Maas
Dept. of Neurosurgery
PO Box 2060
3000 CB Rotterdam
Peter Spronk
Gelre Hospital, location Lukas
PO Box 9014
7300 DS Apeldoorn
Manu Malbrain
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
Mail stop G3-206
Meibergdreef 9
1105 AZ Amsterdam
Saskia Peerderman, Section Editor
Neuro
Dept. of Neurology Intensive Care
PO box 7057
1007 MB Amsterdam
Durk Zandstra
Onze Lieve Vrouwe Gasthuis
PO Box 95500
1090 HM Amsterdam
475
16-08-2006 12:23:43
(advertenties)
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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:
•
Kijkje in -en proeven van- een
•
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
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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,
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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.
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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
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Conclusion section. An abstract should not exceed
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the following sections: Objective - Search strategy
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invited, but occasionally unsolicited editorials may
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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
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inserts (tables or figures), and 15 references. In
addition, writers are encouraged to write one or
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Letters. Only correspondence submitted in reference to a previous publication in NJCC will be
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refers. Please prepare the letter in manuscript
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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
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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].
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a cover letter stating the following: the complete mailing address, E-mail address, telephone
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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
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Tables. Tables should be numbered independently of the figures, with Arabic numerals, with
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be considered for publication, except for review
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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
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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
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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
(advertenties)
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
8/9/06 4:55:36 PM
16-08-2006 12:23:49
55:36 PM
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
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)
479
16-08-2006 12:23:59
Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. 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
480
16-08-2006 12:24:00
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
481
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.
16-08-2006 12:29:50
Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. 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
482
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
16-08-2006 12:29:51
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
483
16-08-2006 12:29:51
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
484
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-
16-08-2006 12:29:51
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.
Reference
1. Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality
rates and functional outcome after subarachnoid
hemorrhage: a systematic review. Stroke 1997;
28(3):660-664.
2. Linn FH, Rinkel GJ, Algra A, van Gijn J. Incidence of
subarachnoid hemorrhage: role of region, year, and
rate of computed tomography: a meta-analysis. Stroke
1996; 27(4):625-629.
3. Wood MJ, Nowitzke AM. Epidemiological aspects
of spontaneous subarachnoid haemorrhage in
Queensland, Australia. J Clin Neurosci 2005; 12(7):770774.
4. Teunissen LL, Rinkel GJ, Algra A, van Gijn J. Risk factors
for subarachnoid hemorrhage: a systematic review.
Stroke 1996; 27(3):544-549.
5. van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001; 124(Pt
2):249-278.
6. van dS, I, Velthuis BK, Wermer MJ et al. New detected
aneurysms on follow-up screening in patients with
previously clipped intracranial aneurysms: comparison with DSA or CTA at the time of SAH. Stroke 2005;
36(8):1753-1758.
7. Ostergaard JR, Reske-Nielsen E, Oxlund H. Histological and morphometric observations on the reticular
fibers in the arterial beds of patients with ruptured
intracranial saccular aneurysms. Neurosurgery 1987;
20(4):554-558.
8. Ruigrok YM, Rinkel GJ, Wijmenga C. Genetics of intracranial aneurysms
1. Lancet Neurol 2005; 4(3):179-189.
9. Haley EC, Jr., Kassell NF, Torner JC. The International
Cooperative Study on the Timing of Aneurysm Surgery. The North American experience. Stroke 1992;
23(2):205-214.
10. Weir B, Grace M, Hansen J, Rothberg C. Time course of
vasospasm in man. J Neurosurg 1978; 48(2):173-178.
11. Sonobe M, Suzuki J. Vasospasmogenic substance produced following subarachnoid haemorrhage, and its
fate. Acta Neurochir (Wien ) 1978; 44(1-2):97-106.
12. Dietrich HH, Dacey RG, Jr. Molecular keys to the
problems of cerebral vasospasm. Neurosurgery 2000;
46(3):517-530.
13. Ehrenreich H, Costa T, Clouse KA et al. Thrombin is a
regulator of astrocytic endothelin-1. Brain Res 1993;
600(2):201-207.
14. Ohlstein EH, Storer BL. Oxyhemoglobin stimulation of
endothelin production in cultured endothelial cells. J
Neurosurg 1992; 77(2):274-278.
15. Kastner S, Oertel MF, Scharbrodt W, Krause M, Boker
DK, Deinsberger W. Endothelin-1 in plasma, cisternal
CSF and microdialysate following aneurysmal SAH.
Acta Neurochir (Wien ) 2005.
16. Kessler IM, Pacheco YG, Lozzi SP, de AA, Jr., Onishi FJ, de
Mello PA. Endothelin-1 levels in plasma and cerebrospinal fluid of patients with cerebral vasospasm after
aneurysmal subarachnoid hemorrhage. Surg Neurol
2005; 64 Suppl 1:S1-S5.
17. Vajkoczy P, Meyer B, Weidauer S et al. Clazosentan
(AXV-034343), a selective endothelin A receptor
antagonist, in the prevention of cerebral vasospasm
following severe aneurysmal subarachnoid hemorrhage: results of a randomized, double-blind, placebocontrolled, multicenter phase IIa study. J Neurosurg
2005; 103(1):9-17.
18. Hughes JT, Schianchi PM. Cerebral artery spasm. A
histological study at necropsy of the blood vessels in
cases of subarachnoid hemorrhage. J Neurosurg 1978;
48(4):515-525.
19. Kubota T, Handa Y, Tsuchida A, Kaneko M, Kobayashi
H, Kubota T. The kinetics of lymphocyte subsets and
macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke 1993; 24(12):19932000.
20. Sercombe R, Dinh YR, Gomis P. Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J
Pharmacol 2002; 88(3):227-249.
21. Osuka K, Suzuki Y, Tanazawa T et al. Interleukin-6 and
development of vasospasm after subarachnoid haemorrhage. Acta Neurochir (Wien ) 1998; 140(9):943-951.
22. Fassbender K, Hodapp B, Rossol S et al. Inflammatory
cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal
cerebral arteries. J Neurol Neurosurg Psychiatry 2001;
70(4):534-537.
23. Kowalski RG, Claassen J, Kreiter KT et al. Initial misdiagnosis and outcome after subarachnoid hemorrhage. JAMA 2004; 291(7):866-869.
24. Linn FH, Rinkel GJ, Algra A, van Gijn J. Headache
characteristics in subarachnoid haemorrhage and
benign thunderclap headache. J Neurol Neurosurg
Psychiatry 1998; 65(5):791-793.
25. van der WN, Rinkel GJ, Hasan D, van Gijn J. Detection
of subarachnoid haemorrhage on early CT: is lumbar
puncture still needed after a negative scan? J Neurol
Neurosurg Psychiatry 1995; 58(3):357-359.
26. van Gijn J, van Dongen KJ. The time course of aneurysmal haemorrhage on computed tomograms.
Neuroradiology 1982; 23(3):153-156.
27. Gunawardena H, Beetham R, Scolding N, Lhatoo SD.
Is cerebrospinal fluid spectrophotometry useful in CT
scan-negative suspected subarachnoid haemorrage?
Eur Neurol 2004; 52(4):226-229.
28. O’Connell DM, Watson ID. Definitive angiographic
detection of subarachnoid haemorrhage compared
with laboratory assessment of intracranial bleed in
CT-negative patients. Ann Clin Biochem 2003; 40(Pt
3):269-273.
29. Wood MJ, Dimeski G, Nowitzke AM. CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage. J Clin Neurosci 2005;
12(2):142-146.
30. Cloft HJ, Joseph GJ, Dion JE. Risk of cerebral angiography in patients with subarachnoid hemorrhage,
cerebral aneurysm, and arteriovenous malformation:
a meta-analysis. Stroke 1999; 30(2):317-320.
31. Wardlaw JM, White PM. The detection and management of unruptured intracranial aneurysms. Brain
2000; 123 ( Pt 2):205-221.
32. Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity
in basal cerebral arteries. J Neurosurg 1982; 57(6):769774.
33. Laumer R, Steinmeier R, Gonner F, Vogtmann T, Priem
R, Fahlbusch R. Cerebral hemodynamics in subarachnoid hemorrhage evaluated by transcranial Doppler
sonography. Part 1. Reliability of flow velocities in
clinical management. Neurosurgery 1993; 33(1):1-8.
485
16-08-2006 12:29:52
34. Mascia L, Fedorko L, terBrugge K et al. The accuracy of
transcranial Doppler to detect vasospasm in patients
with aneurysmal subarachnoid hemorrhage. Intensive
Care Med 2003; 29(7):1088-1094.
35. Astrup J, Siesjo BK, Symon L. Thresholds in cerebral ischemia - the ischemic penumbra. Stroke 1981; 12(6):723725.
36. Vespa PM, Nuwer MR, Juhasz C et al. Early detection of
vasospasm after acute subarachnoid hemorrhage using
continuous EEG ICU monitoring. Electroencephalogr
Clin Neurophysiol 1997; 103(6):607-615.
37. Claassen J, Hirsch LJ, Kreiter KT et al. Quantitative continuous EEG for detecting delayed cerebral ischemia in
patients with poor-grade subarachnoid hemorrhage.
Clin Neurophysiol 2004; 115(12):2699-2710.
38. Heran NS, Hentschel SJ, Toyota BD. Jugular bulb oximetry for prediction of vasospasm following subarachnoid
hemorrhage. Can J Neurol Sci 2004; 31(1):80-86.
39. Hoffman WE, Wheeler P, Edelman G, Charbel FT, Torres
NJ, Ausman JI. Hypoxic brain tissue following subarachnoid hemorrhage. Anesthesiology 2000; 92(2):442-446.
40. Hutchinson PJ, Al Rawi PG, O’Connell MT et al. Monitoring of brain metabolism during aneurysm surgery
using microdialysis and brain multiparameter sensors.
Neurol Res 1999; 21(4):352-358.
41. Kett-White R, Hutchinson PJ, Al Rawi PG et al. Cerebral
oxygen and microdialysis monitoring during aneurysm
surgery: effects of blood pressure, cerebrospinal fluid
drainage, and temporary clipping on infarction. J Neurosurg 2002; 96(6):1013-1019.
42. Unterberg AW, Sakowitz OW, Sarrafzadeh AS, Benndorf
G, Lanksch WR. Role of bedside microdialysis in the
diagnosis of cerebral vasospasm following aneurysmal
subarachnoid hemorrhage. J Neurosurg 2001; 94(5):740749.
43. Nilsson OG, Brandt L, Ungerstedt U, Saveland H. Bedside detection of brain ischemia using intracerebral
microdialysis: subarachnoid hemorrhage and delayed
ischemic deterioration. Neurosurgery 1999; 45(5):11761184.
44. Cremer OL, van Dijk GW, van WE et al. Effect of intracranial pressure monitoring and targeted intensive care on
functional outcome after severe head injury. Crit Care
Med 2005; 33(10):2207-2213.
486
45. Fujii Y, Takeuchi S, Sasaki O, Minakawa T, Koike T, Tanaka
R. Ultra-early re-bleeding in spontaneous subarachnoid
hemorrhage. J Neurosurg 1996; 84(1):35-42.
46. Hijdra A, Vermeulen M, van Gijn J, van Crevel H. Rerupture of intracranial aneurysms: a clinicoanatomic study.
J Neurosurg 1987; 67(1):29-33.
47. Kassell NF, Torner JC. Aneurysmal rebleeding: a preliminary report from the Cooperative Aneurysm Study.
Neurosurgery 1983; 13(5):479-481.
48. Brilstra EH, Rinkel GJ, Algra A, van Gijn J. Rebleeding,
secondary ischemia, and timing of operation in patients
with subarachnoid hemorrhage. Neurology 2000;
55(11):1656-1660.
49. Ohman J, Heiskanen O. Timing of operation for ruptured supratentorial aneurysms: a prospective randomized study. J Neurosurg 1989; 70(1):55-60.
50. Nieuwkamp DJ, de Gans K, Algra A et al. Timing of
aneurysm surgery in subarachnoid haemorrhage - an
observational study in The Netherlands. Acta Neurochir
(Wien ) 2005; 147(8):815-821.
51. Guglielmi G, Vinuela F, Duckwiler G et al. Endovascular treatment of posterior circulation aneurysms by
electrothrombosis using electrically detachable coils. J
Neurosurg 1992; 77(4):515-524.
52. Molyneux A, Kerr R, Stratton I et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with
ruptured intracranial aneurysms: a randomised trial.
Lancet 2002; 360(9342):1267-1274.
53. Molyneux AJ, Kerr RS, Yu LM et al. International
subarachnoid aneurysm trial (ISAT) of neurosurgical
clipping versus endovascular coiling in 2143 patients
with ruptured intracranial aneurysms: a randomised
comparison of effects on survival, dependency, seizures,
rebleeding, subgroups, and aneurysm occlusion. Lancet
2005; 366(9488):809-817.
54. van dS, I, Algra A, Wermer M et al. Endovascular coiling
versus neurosurgical clipping for patients with aneurysmal subarachnoid haemorrhage. Cochrane Database
Syst Rev 2005; 4:CD003085.
55. Rinkel GJ, Feigin VL, Algra A, van den Bergh WM, Vermeulen M, van Gijn J. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database
Syst Rev 2005;(1):CD000277.
56. van den Bergh WM, Algra A, van der Sprenkel JW,
Tulleken CA, Rinkel GJ. Hypomagnesemia after aneurysmal subarachnoid hemorrhage. Neurosurgery 2003;
52(2):276-281.
57. van den Bergh WM, Algra A, van Kooten F et al. Magnesium sulfate in aneurysmal subarachnoid hemorrhage:
a randomized controlled trial. Stroke 2005; 36(5):10111015.
58. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with pravastatin
on cerebral vasospasm, autoregulation, and delayed
ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial.
Stroke 2005; 36(8):1627-1632.
59. Rosenwasser RH, Delgado TE, Buchheit WA, Freed MH.
Control of hypertension and prophylaxis against vasospasm in cases of subarachnoid hemorrhage: a preliminary report. Neurosurgery 1983; 12(6):658-661.
60. Rinkel GJ, Feigin VL, Algra A, van Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid
haemorrhage. Cochrane Database Syst Rev 2004;(4):
CD000483.
61. Sen J, Belli A, Albon H, Morgan L, Petzold A, Kitchen N.
Triple-H therapy in the management of aneurysmal
subarachnoid haemorrhage. Lancet Neurol 2003;
2(10):614-621.
62. Duckles SP. Innervation of the cerebral vasculature. Ann
Biomed Eng 1983; 11(6):599-605.
63. Manno EM, Gress DR, Schwamm LH, Diringer MN,
Ogilvy CS. Effects of induced hypertension on transcranial Doppler ultrasound velocities in patients after
subarachnoid hemorrhage. Stroke 1998; 29(2):422-428.
64. Muizelaar JP, Becker DP. Induced hypertension for the
treatment of cerebral ischemia after subarachnoid
hemorrhage. Direct effect on cerebral blood flow. Surg
Neurol 1986; 25(4):317-325.
65. Joseph M, Ziadi S, Nates J, Dannenbaum M, Malkoff M.
Increases in cardiac output can reverse flow deficits
from vasospasm independent of blood pressure: a
study using xenon computed tomographic measurement of cerebral blood flow. Neurosurgery 2003;
53(5):1044-1051.
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Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. Received March 2006; accepted in revised form May 2006
r e v i e w
Electrical impedance tomography
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
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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rel.
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.
488
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
490
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-
16-08-2006 12:35:12
0
-100
density (HU)
0
-0.1
-300
-400
-500
0.1
0
-100
0
-0.1
-200
-300
-400
-500
-0.2
0
0.1
-100
0
density (HU)
rel. impedance change
-200
-0.2
density (HU)
0.1
-0.1
-0.2
0
10
20
time (s)
30
40
0
10
20
time (s)
30
40
-200
-300
-400
-500
0
4
8
12
0
time (s)
4
8
12
time (s)
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.
492
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.
16-08-2006 12:35:14
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.
493
16-08-2006 12:35:14
Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. Received March 2006; accepted in revised form July 2006
r e v i e w
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
494
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
16-08-2006 12:35:15
6000
Inspiration
Lung volume (ml)
5000
4000
Inspiratory
Reserve Volume
Total
Vital
Lung
Capacity
Capacity
3000
Inspiratory
Capacity
Tidal
Volume
2000
1000
Vtrapped
Expiratory Flow Obstruction
Expiratory
Reserve Volume
Residual
Volume
Functional
Residual
Capacity
Expiration
Time
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
Alveolar Pressure
(cmH20)
495
10
0
PEEPi
16-08-2006 12:35:15
20
Alveolar Pressure
(cmH20)
10
PEEPi
0
Inspiratory 1 .0
Air Flow l.s -1
0
Expiratory 1 .0
Expiratory Flow Obstruction
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.
496
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.
16-08-2006 12:35:16
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.
497
16-08-2006 12:49:50
Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. Received January 2006; accepted in revised form July 2006
r e v i e w
Critical Care and Emergency Research in the European Union
under the European Clinical Trials Directive 2001/20/EC:
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
498
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
16-08-2006 12:49:51
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
499
16-08-2006 12:49:51
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?
500
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-
16-08-2006 12:49:52
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.
5.
6.
7.
8.
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.
21.
22.
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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Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. 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
502
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-
16-08-2006 12:53:52
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-
503
16-08-2006 12:53:53
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.
504
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
16-08-2006 12:53:54
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.
505
16-08-2006 12:53:54
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.
References
1. Checchia PA, Broniki RA, Costello JM, et al. 2005.
Steroid use before pediatric cardiac operations using
cardiopulmonary bypass: an international survey of 36
centers. Pediatr Crit Care Med.6:495-6
2. Motsay GJ, Alho A, Jaeger T, et al. 1970. Effects of corticosteroids on the circulation in shock: experimental
and clinical results. Fed Proc.2 9:1861-73
3. Novak E, Stubbs SS, Seckman CE, et al.1970. Effects of
a single large intravenous dose of methylprednisolone
sodium succinate. Clin Pharmacol Ther.11:711-7
4. Dietzman RH, Castaneda AR, Lillehei CW, et al.1970.
Corticosteroids as effective vasodilators in the treatment of low output syndrome. Chest.57:440-53
5. Boscoe MJ, Yewdall VMA, Thompson MA, et al. 1983.
Complement activation during cardiopulmonary
bypass: quantitative study of effects of methylprednisolone and pulsatile flow. BMJ. 287:1747-1750
6. Tassani P, Richter JA, Barankay A et al. 1999. Does highdose methylprednisolone in aprotinin-treated patients
attenuate the systemic inflammatory response during
coronary artery bypass grafting procedures? J Cardiothorac Vasc Anesth.13:165-72
7. Yared JP, Starr NJ, Torres FK, et al. 2000. Effect of single
dose, postinduction dexamethasone on recovery after
cardiac surgery. Ann Thorac Surg. 69:1420-4
8. Chaney MA, Durazu-Arvizu RA, Nikolov MP, et al.
2001. Methylprednisolone does not benefit patients
undergoing coronary artery bypass grafting and early
tracheal extubation. J Thorac Cardiovasc Surg. 121:561-9
9. Chaney MA, Nikolov MP, Blakeman BP, et al.1999.
Hemodynamic effects of methylprednisolone in
patients undergoing cardiac operation and early extubation. Ann Thorac Surg. 67:1006-11
10. Lindberg L, Forsell C, Jogi P, et al. 2003. Effects of
dexamethasone on clinical course, C-reactive protein,
S100B protein and von Willebrand factor antigen after
paediatric cardiac surgery. Br J Anaesth. 90:728-32
506
11. Checchia PA, Backer CL, Bronicki RA, et al. 2003. Dexamethasone reduces postoperative troponin levels in
children undergoing cardiopulmonary bypass. Crit Care
Med. 31:1742-5
12. Butler J, Pathi VL, Paton RD, et al.1996. Acute-Phase
response to cardiopulmonary bypass in children
weighing less than 10 kilograms. Ann Thorac Surg.
62:538-42
13. Schroeder VA, Pearl JM, Schwartz SM, et al. 2003.
Combined steroid treatment for congenital heart
surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation.
107:2823-8
14. Duffy JY, Nelson DP, Schwartz SM, et al.2004. Glucocorticoids reduce cardiac dysfunction after cardiopulmonary bypass and circulatory arrest in neonatal piglets.
Pediatr Crit Care Med. 5:28-34
15. Lodge AJ, Chai PJ, Daggett CW, et al.1999. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose
is important. J Thorac Cardiovasc Surg. 117:515-22
16. Mott AR, Fraser CD Jr, Kusnoor AV, et al. 2001. The
effect of short term prophylactic methylprednisolone
on the incidence and severity of postpericardiotomy
syndrome in children undergoing cardiac surgery with
cardiopulmonary bypass. J Am Coll Cardiol. 37:1700-6
17. Booker PD, Prosser DP, Franks R. 1996. Effect of hypothermia on rectal mucosal perfusion in infants undergoing cardiopulmonary bypass. Br J Anaesth. 77:591-6
18. Booker PD, Romer H, Franks R. 1996. Gut mucosal perfusion in neonates undergoing cardiopulmonary bypass.
Br J Anaesth. 77:597-602
19. Lerberg DB, Hardesty RL, Siewers RD, et al. 1982. Coarctation of the aorta in infants and children: 25 years of
experience. Ann Thorac Surg. 33:159-70
20. Menzies IS, Laker MF, Pounder R, et al. 1979. Abnormal
intestinal permeability to sugar in villous atrophy. Lancet. ii,1107-9
21. Beach RC, Menzies IS, Clayden GS, et al.1982. Gastrointestinal permeability changes in the preterm neonate.
Arch Dis Child. 57:141-5
22. Miki K, Butler R, Moore D, et al. 1996. Rapid and simultaneous quantification of rhamnose, mannitol and
lactulose by HPLC for estimating intestinal permeability in paediatric practice. Clin Chem. 42:71-5
23. Van Elburg RM, Uil JJ, De Monchy, et al.1992. Intestinal
permeability in pediatric gastroenterology. Scan J Gastroenterol. 27:19-24
24. Hellemeesch MM, Lamers WH, Soeters PB, et al. 2000.
Increased lactulose/rhamnose ratio during fluid load is
caused by increased urinary lactulose excretion. Am J
Physiol Gastrointest Liver Physiol. 278:G83-8
25. Fink MP. 1997. Interpreting dual-sugar absorption studies in critically ill patients; what are the implications of
apparent increase in intestinal permeability to hydrophilic solutes? Intensive Care Med. 23:489-92
26. Malagon I, Onkenhout W, Klok M, et al. 2005. Gut
permeability in neonates after stage 1 Norwood procedure. Pediatr Crit Care Med. 6:614-5
27. Malagon I, Onkenhout W, Klok M, et al. 2006. Rhamnose and rhamnitol in dual sugar permeability tests.
JPGN (in press).
28. Malagon I, Onkenhout W, Klok G, et al. 2005. Gut permeability in paediatric cardiac surgery. Br J Anaesth.
94: 181-5
29. Colgan SP, Parkos CA, Matthews JB, et al.1994. Interferon-gamma induces a cell surface phenotype switch
on T84 intestinal epithelial cells. Am J Physiol. 267:
C402-10
30. Madsen KL, Lewis SA, Tavernini MM, et al.1997. Interleukin 10 prevents cytokine-induced disruption of T84
monolayer barrier integrity and limits chloride secretion. Gastroenterology. 113:151-9
31. Malagon I, Onkenhout W, Klok M, et al. 2005. Dexamethasone reduces gut permeability in pediatric
cardiac surgery. J Thorac Cardiovasc Surg. 130:265-71
16-08-2006 14:11:10
32. Hebra A, Brown MF, Hirshl RB, et al.1993. Mesenteric
ischemia in hypoplastic left heart syndrome. J Pediatr
Surg. 28:606-11
33. Jeffries HE, Wells WJ, Starnes VA, et al. 2006. Gastrointestinal morbidity after Norwood palliation for hypoplastic left heart syndrome. Ann Thorac Surg. 81:982-7
34. Harrison AM, Davis S, Reid JR, et al. 2005. Neonates
with hypoplastic left heart syndrome have ultrasound
evidence of abnormal superior mesenteric artery perfusion before and after modified Norwood procedure.
Pediatr Crit Care Med. 6:445-7
35. Kemp M, Donovan J, Higham H, Hooper J. 2004 Biochemical markers of myocardial injury. Br J Anaesth.
93:63-73
36. Immer FF, Stocker FP, Seiler AM, et al.1998. Comparison
of Troponin-I and Troponin-T after pediatric cardiovascular operation. Ann Thorac Surg. 66:2073-7
37. Immer FF, Stocker F, Seiler AM, et al.1997. Troponin-T;
improved diagnostic assessment of myocardial damage
in childhood. Acta Paediatr. 86: 1321-7
38. Hovels-Gurich HH, Vazquez-Jimenez JF, Silvestri A, et
al.2002. Production of proinflammatory cytokines and
myocardial dysfunction after arterial switch operation
in neonates with transposition of the great arteries. J
Thorac Cardiovasc Surg. 124: 811-20
39. Immer FF, Stocker FP, Seiler AM, et al.1998. Comparison
of Troponin-I and Troponin-T after pediatric cardiovascular operation. Ann Thorac Surg. 66: 2073-7
40. Lipshultz SE, Somers MJG, Lipsitz SR, et al. 2003. Serum
cardiac troponin and subclinical cardiac status in pediatric chronic renal failure. Pediatrics 112:79-86
41. Sasse S, Brand NJ, Kyprianou P, et al.1993 Troponin I
gene expression during human cardiac development
and in end-stage heart failure. Circ Res. 72: 932-8
42. Pees C, Haas NA, von der Beek J, et al. 2003. Cardiac troponin I is increased after interventional closure of atrial
septal defects. Catheter Cardiovasc Interv 58:124-9
43. Modi P, Imura H, Angelini GD, et al. 2003. Pathologyrelated troponin I release and clinical outcome after
pediatric open heart surgery. J Card Surg. 18:295-300
44. De Hert SG, ten Broecke PW, Mertens E, et al. 2002.
Sevoflurane but not propofol preserves myocardial
function in coronary surgery patients. Anesthesiology.
97: 42-9
45. De Hert SG, van der Linden PJ, Cromheecke S, et al.
2004. Choice of primary anesthetic regimen can influence intensive care unit length of stay after coronary
surgery with cardiopulmonary bypass. Anesthesiology.
101: 9-20
46. Malagon I, Hogenbirk K, van Pelt J, et al. 2005. Effect of
three different anaesthetic agents on the postoperative
production of cardiac troponin T in paediatric cardiac
surgery. Br J Anaesth. 94:805-9
47. Kathiresan S, Servoss SJ, Newell JB, et al. 2004. Cardiac
troponin T elevation after coronary artery bypass grafting is associated with increased one-year mortality. Am
J Cardiol. 94:879-81
48. Malagon I, Hogenbirk K, van Pelt J, et al. 2005. Effect of
dexamethasone on postoperative cardiac troponin T
production in pediatric cardiac surgery. Intensive Care
Med. 31:1420-6
49. Nagy ZL, Collins M, Sharpe T, et al. 2003. Effect of two
different bypass techniques on the serum troponin-T
levels in newborn and children. Does pH-stat provide
better protection? Circulation. 108:577-82
50. Hasegawa T, Yoshimura N, Oka S, et al. 2004 Evaluation
of heart fatty acid-binding protein as a rapid indicator
for assessment of myocardial damage in pediatric cardiac surgery J Thorac Cardiovasc Surg. 127:1697-702
51. Schwartz SM, Duffy JY, Pearls JM, et al 2003. Glucocorticoids preserve calpastatin and troponin I during
cardiopulmonary bypass in immature pigs. Pediatr Res.
54:91-7
52. Imura H, Caputo M, Parry A, et al. 2001. Age-dependent
and hypoxia-related differences in myocardial protection during pediatric open heart surgery. Circulation.
103: 1551-6
53. Ashraf SS, Tian Y, Zacharrias S, et al. 1997. Effect of
cardiopulmonary bypass on neonatal and paediatric
inflammatory profiles. Eur J Cardiothorac Surg. 12:862-8
54. Bronicki RA, Backer CL, Baden HP, et al. 2000. Dexamethasone reduces the inflammatory response to
cardiopulmonary bypass in children. Ann Thorac Surg.
69:1490-5
55. Lichtman SM. Bacterial translocation in humans. 2001.
JPGN. 33:1-10
56. De-Souzza DA, Greene LJ. 2005. Intestinal permeability
and systemic infections in critically ill patients: Effect of
glutamine. Crit Care Med. 33:1125-35
507
16-08-2006 12:53:55
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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
g
vrouw
Functie
Telefoonnummer
Faxnummer
E-mail adres
g
Ik kom naar de training voor IC kwaliteitsvisitateurs op 22 september 2006
g
Ontvangt hiervoor graag reiskostenvergoeding
g
Ik bestel een dagretour treinkaartje.
(De Reehorst ligt naast het NS Intercity station Ede-Wageningen).
g
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 /
U kunt ook gebruik maken van het gratis antwoordnummer:
NVIC secretariaat visitatie
Antwoordnummer 2459
6710 WB Ede
16-08-2006 12:55:06
4
L
ce aat
l o de
ng hu
em m
oe ane
id
Fungal Cell Wall
Fungal Cell Wall
CANCIDAS
Cell
Membrane
Cell
Membrane
ß(1,3)-D-glucan
Precursors to ß(1,3)-D-glucan
Precursors to ß(1,3)-D-glucan
Normal Cell-Wall Synthesis
Synthesis Inhibited by CANCIDAS
• Invasieve candidiasis
• Invasieve aspergillose
• Empirische antifungale therapie
1
CANDIDA ALBICANS
3
C.
C . rugo
C. gla b s a
C. pararata
C. trop p s i l
o
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i
C. i p o e r m
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C. d u b y t i c o n d
l a ii
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lu r ns
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CANDIDA NON-ALBICANS
ASPERGILLUS
• Bewezen effectiviteit
• Gunstig veiligheidsprofiel
1
0307CAN06NL155J0306
4
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.
• NVIC Infectiecongres 2007: November 8th – 9th, Hotel
en Congrescentrum De Reehorst, Ede, the Netherlands.
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
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
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
Drs. F. Nooteboom, Viecuri Medisch Centrum, Venlo
Dr. K.H. Polderman, VUMC, Amsterdam
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
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
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
Drs. M.I. Fokkema, Universitair Medisch Centrum,
Groningen
Drs. M.G.E.C. Hilkens, Radboud Universiteit
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
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
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
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
(voorzitter)
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
(voorzitter)
Dr. S.J.A. Aerdts, Isala Klinieken, Zwolle
Prof. Dr. G.J. Scheffer, Radboud Universiteit
Sophia, Rotterdam
Ede
Bestuurscommissie FCCS Nederland
Drs. F. Nooteboom, VieCuri MC, Venlo (voorzitter)
Drs. B.M. van der Kolk, Radboud Universiteit
Drs. L.M. Lambalk, Westfries Gasthuis, Hoorn
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
Drs. E.F. Salm, Reinier de Graaf Gasthuis, Delft
Drs. J.M.M. Verwiel, Radboud Universiteit Nijmegen
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
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
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
ESICM Cobatrice
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
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.
Drs. B.M. van der Kolk
Chirurg-intensivist
Universitair Medisch Centrum
St. Radboud, Nijmegen
Penningmeester
Drs. J.H.J. Meeder
Anesthesioloog-intensivist
Medisch Centrum Rijnmond-Zuid,
Rotterdam
Secretaris
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
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
Prof. Dr. D. Tibboel
Kinderarts-intensivist
Erasmus MC Sophia Kinder
ziekenhuis, Rotterdam
Bestuurslid
Drs. C.P.C. de Jager
Jeroen Bosch Ziekenhuis, Den Bosch
Bestuurslid
Secretariaat NVIC:
Stationsweg 73 C, 6711 PL Ede.
Telefoon: 0318-693337,
Fax: 0318-693338,
Drs. A.M.G.A. de Smet
Universitair Medisch Centrum,
Utrecht
NVVC
13 pnt
NVA
13 uur
NVK
14 uur
NVZA
14 uur
NIV
14 uur
NVvH
16 pnt
NVVM
14 pnt
NVN
0 pnt
NVALT
14 pnt
NVTC
toegekend
xxxx
11 pnt
12 pnt
12 pnt
12 pnt
12 pnt
-
12
11 pnt
toegekend
11 pnt
11 pnt
11 pnt
11 pnt
12 pnt
12 pnt
-
0
11 pnt
toegekend
16-08-2006 12:55:12
advertentie NJCC
16-08-2006
13:28
Pagina 1
advert
nvic
a
w
a
r
d
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
(advertenties)
aankondiging
Algemene
ledenvergadering
21 september 2006
20.00 uur
Lokatie:
Restaurant Het Oude
Politiebureau,
Breelaan 2A te Ede
16-08-2006 13:32:33
algemen e i n for mati e
j a a r p r o g r a m m a
n v i c
a c t i v i t e i t e n
37
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
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
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
Erasmus MC Dijkzigt, Rotterdam
Prof Dr ABJ Groeneveld
VU Medisch Centrum, Amsterdam
Drs A Manten
Meander Medisch Centrum,
Amersfoort
Drs JMM Verwiel
Radboud Universiteit Nijmegen
Medisch Centrum
Dr MJM Bonten
Internist-infectioloog
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
Groningen
Dr LMA Heunks
Longarts i.o.
Medisch Centrum
Drs DHT Tjan
Ziekenhuis Gelderse Vallei, Ede
Dr RFE Wolf
Radioloog
Groningen
Drs DA Dongelmans
Academisch Medisch Centrum,
Amsterdam
Prof Dr JG van der Hoeven
Medisch Centrum
Dr JE Tulleken
Groningen
Drs ARH van Zanten
Ziekenhuis Gelderse Vallei, Ede
(advertenties)
activiteiten nvic
•Deadline indienen van
abstracts voor de Nederlandse
Intensivistendagen 2007
multidisciplinair congres
voor arts-assistenten/fellows op de IC, specialisten met
belangstelling voor IC, IC-verpleegkundigen.
ziekenhuisinstrumentatietechnici, klinisch fysici, ziekenhuisapothekers
1 november 2006
CongresHotel ‘De Werelt’ Lunteren
1 oktober 2006
• NVIC Mechanische
Beademingsdagen
30 november en 1 december 2006
• FCCS
www.fccs.nl
• NVIC Nederlandse
Intensivistendagen 2007
31 januari, 1 en 2 februari 2007
Thema: Update in Intensive Care
Kennissessies en workshops over o.a. de laatste nieuwe
beademingsvormen zoals: ASV, SMARTCARE
en (voor het eerst in Nederland) NAVA
Inschrijving aan de zaal of via:
www.topicsinic.nl
16-08-2006 13:32:36
523
r e g i s t r at i e f o r m u l i e r
Lidmaatschap (altijd invullen !)
Ben lid van de nvic Schrijf mij in als lid van de nvic
Wil geen lid worden van de nvic
Wil post ontvangen op <
< (lidmaatschap 2006, inclusief netherlands journal of critical care)
<
< privé-adres
< werk-adres
Man < Vrouw
Naam
<
Registratienummer < < < < < <
Voorletters
Titulatuur
Adres
Postcode/Woonplaats
Telefoon privé
Fax
E-mail-adres
Geboortedatum
Bankrekeningnummer <<<<<<<<<
Girorekeningnummer <<<<<<<<<
Beroep
I
medisch specialist <
Tnv/Plaats
Tnv/Plaats
geregistreerd intensivist <
specialisme:
registratiedatum IC:
aandachtsgebied:
registratiedatum:
II arts-assistent < agio
specialisme:
aandachtsgebied:
verwachte registratiedatum:
< agnio < anders:
Ziekenhuis/Instelling
Afdeling
Adres
Postcode/Woonplaats
Telefoon
Sein
Fax
E-mail-adres
Ben voor NJCC_04 binnenwerk 01.indd 523
% (percentage) werkzaam op de Intensive Care afdeling
Z.O.Z.
16-08-2006 13:38:42
r e g i st r at i e f o r m u l i e r
co n g r e s s e n , c u rsusse n e n symposia
Alle congressen, cursussen en symposia zijn inclusief een gratis reader
le de n n i euwe le de n
n i e t- l e d e n
< €575 < €575 < €575 < €575 < €575 < €575 < €575 < €575 < €575 < €575 < €575 < €575 < €650
< €650
< €650
< €650
< €650
< €650
< €650
< €650
< €650
< €650
< €650
< €650
< € 240,- < € 315,- < € 350,-
< € 95,- < € 15,50 < € 25,- < € 19,50 < € 29,50 < € 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