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![Page 1: Strategies to reduce the risk of contrast nephropathy: an evidence-based approach Neesh Pannu and Marcello Tonelli, Current opinion in nephrology and hypertension.](https://reader036.fdocuments.in/reader036/viewer/2022070309/551d9da0497959293b8ce886/html5/thumbnails/1.jpg)
Strategies to reduce the risk of contrast nephropathy: an evidence-based approach
Neesh Pannu and Marcello Tonelli, Current opinion in nephrology and hypertension 2006
Norbert Mayaud, interne CHU Saint étienne
DESC de réanimation médicale, LYON 2006
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La néphropathie aux produits de contraste
• Responsable de 10% des IRA (3ème cause)
• L’incidence des néphropathie de contraste est basse 1,6-2,3%, mais elle est plus élevée chez les patients après une PCI 1,5%-13%
• Le risque de nécessiter une dialyse transitoire voir définitive est faible mais non nul
• RR de mortalité multiplié par 6
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Mécanismes
• Baisse perfusion rénale due à hypoxie régionale
• stress oxydatif induit par les radicaux libres
• Toxicité tubulaire directe
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Définition néphropathie aux produits de contraste iodés (NPC)
• Augmentation de créatininémie dans les 3 jours suivant l ’injection intra-vasculaire de produit de contraste
• Augmentation de créatininémie de plus de 25% ou de 44 µmol/l (0,5 mg/dl)
• Absence d ’autre cause
MORCOS SK, THOMSEN HS et al. « Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committe, European Society of Urogenital Radiology (ESUR) » Eur Radiol 1999; 9:1602-1613.
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JACC 2004
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1950 HIGHOSMOLALITYCONTRAST
MEDIA(HOCM)
OSMOLALITEPLASMA X 8
> 1500mOsmol/kg
Diatrizoate
1980 « LOW »OSMOLALITYCONTRAST
MEDIA(LOCM)
OSMOLALITEPLASMA x 2 à
3
550-850mOsmol/kg
IohexolIopamidolioxaglate
OMNIPAQUEIOPAMIRONHEXABRIX
1990 ISOOSMOLALITYCONTRAST
MEDIA(IOCM)
OSMOLALITEIDEM
PLASMA
290 mOsml/kg Iodixanol(étude
NEPHRIC)
VISIPAQUE
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NEJM 2003
• Etude randomisée, double aveugle, prospective, multicentrique, portant sur 129 patients diabétiques en insuffisance rénale ayant bénéficiés d’une coro ou d’une artériographie
Iodixanol VISIPAQUE*:, iso-osmolaire
Iohexol OMNIPAQUE*: hypo-osmolaire
2/64
17/65
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Kidney International, Vol. 68 (2005), pp. 2256–2263The role of osmolality in the incidence of contrast-inducednephropathy: A systematic review of angiographic contrast
media in high risk patientsRICHARD SOLOMON
Fletcher Allen Health Care, Burlington, Vermont
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Quelles sont les stratégies préventives ?
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N-acétylcystéine
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mécanismes
• Capteurs de radicaux libres
• Effet sur vasodilatation du NO
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Etude princeps de Tepel et al. N Engl J Med 2000
• Étude randomisée montrant la diminution de 90% du risque de néphropathie induite par l’iode chez des malades à risque (IRC) dans le groupe recevant du N-acétylcystéine per os 2 fois par jour la veille et le jour du scanner par rapport au groupe placebo
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Métanalyse de Birck et al. Lancet 2003
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Pannu et al. Current opinion in nephrology and hypertension 2006
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Problème de l’hétérogénéité importante entre les essais
• Le critère principal étudié • La sélection des patients• Le choix du produit de contraste• Le type d’examen• La dose, la voie d’administration et le
protocole d’administration du N-acétylcystéine
• L’hydrataion IV associée
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Les récentes études prospectives
• Webbs et al. Am Heart J 2004
Étude randomisée portant sur 487 patients en IR, recevant avant leur PCI (utilisant du ioversol)
soit hydratation IV + placebo
soit hydratation IV + mucomyst 500mg IV
Critère principal négatif : (baisse de la clairance de plus 5ml/min )
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• Azmus et al. J Invasive Cardiol 2006Étude randomisée portant sur 397 patients en
IR, recevant avant leur PCI (utilisant haute et basse osmolarité)
soit hydratation IV + placebo soit hydratation IV + mucomyst 600mg 4
fois avant et une fois aprèsPas de différence significative sur incidence
de NPC (8,4 7,1)
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• Gomes et al. Heart 2005
Étude randomisée portant 156 patients en IR recevant avant leur PCI, (low osmolaire)
soit hydratation IV + placebo
soit hydratation IV + 600 mg 2 fois avant et après
pas de différence significative (10,4 10,1)
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N-Acétylcystéine and contrast-induced Nephropathy in primary angioplasty
Marenzi G et al N Engl J Med 2006
• Patients bénéficiant d’une angioplastie primaire
• 354 patients consécutifs
• 116 ont reçu 600mg IV avant et 600 mg per os 2 fois par jour pendant 48h
• 119 ont reçus une double dose à 1200mg
• 119 placebo
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Incidence of Contrast-Medium-Induced Nephropathy in the Three Study Groups Stratified According to the Creatinine Clearance Rate and Left Ventricular Ejection Fraction (LVEF)
Marenzi G et al. N Engl J Med 2006;354:2773-2782
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La N-acétylcystéine intraveineuse et orale pourrait prévenir la néphropathie induite par les produits de contraste chez les patients bénéficiant d’une angioplastie primaire,
avec un effet dose-dépendant, et elle pourrait améliorer le pronostic
intrahospitalier
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Théophylline
Bagshaw and ghali Arch Intern Med 2005
Les auteurs ont analysés 9 études randomisées comparant l’administration orale et IV de théophylline avant procédure avec PC
pas de différence significative
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Fenoldopam• agoniste spécifique du récepteur de la dopamine: pourrait augmenter le flux sanguin rénal cortical et médullaire après produit de contraste, premières études prometteuses chez l’animal
Stone et al, JAMA 2003 : étude prospective randomisée, double aveugle, multicentrique, contre placebo, 315 patients. Aucun effet préventif sur IRA.
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Acide ascorbique
Antioxydant
Spargias et al, circulation 2004, montre une différence significative chez 231 patients recevant une PCI
Première étude demande études complémentaires
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Stratégie préventive de néphropathie aux produits de
contraste
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• Évaluer le rapport bénéfice-risque pour le patient (indication/facteurs de risques)
• Rechercher autre mode d’exploration • Respecter un intervalle de 8 jours entre deux injection de
produits iodés• Limitée la dose d’injection• Choix du produit de contraste • Supprimer les traitements néphrotoxiques• Arrêter les diurétiques 24h avant l’examen si la situation le
permet• Hydrater le patient avec 1 l de sérum salé isotonique 12h avant
et 12h après si la fonction cardiaque le permet
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Problème du mucomyst
Pour les patients présentant un risque important de NPC l’utilisation de N-acétylcystéine (>1200mg par dose) peut être considérée
1,6 euros pour 2400mg
Absence d’effets indésirables
La demande d’AMM ne viendra sûrement pas du laboratoire fabricant ce médicament mis sur le marché depuis 1984…