Ca faisait longtemps que je voulais me faire une petite mise au point sur le paracétamol. En anesthésie nous prescrivons quotidiennement ce médicament pour lutter contre la douleur post-opératoire. On connait mal les voies d’action du paracétamol mais on nous enseigne l’analgésie multi-modale : en ciblant des voies de la douleur différentes des voies bloquées par les morphiniques on optimiserait la prise en charge des patients. Quid ?Back to basics. Le paracétamol, comment ça fonctionne ?
La biodisponibilité du paracétamol est variable mais globalement bonne par voie orale, beaucoup plus variable et imprévisible par voie rectale. L’utilisation de comprimés effervescents et la voie IV améliore la rapidité d’action. En 20 minutes une diminution de la douleur peut être ressentie vs 45 minutes pour des comprimés classiques.
Une fois biodisponible, que fait le paracétamol ? les données sont multiples, reflétant nos connaissances en neurophysiologie… Le paracétamol peut agir au niveau central en diminuant la capacité des COX à produire des prostaglandines. Cet effet n’existe pas en périphérie où le stress oxydant lié à la lésion maintient les COX actives. Le paracétamol a une action de modulation positive des opioïdes endogènes à l’interface entre le cerveau et la moelle (renforcement d’une voie supraspinale vers la moelle). Ensuite le paracétamol interagit avec les voies sérotoninergiques descendantes en renforcant leur action. On trouve des interactions avec des systèmes complexes de métabolisme du NO et des cannabinoïdes endogènes. (On a craint des interactions avec les antiémétiques comme l’ondansétron, mais l’un ne semble pas gommer les effets de l’autre)
Le paracétamol est essentiellement éliminé par le foie où il est métabolisé à 90% par glucurono- et sulpho-conjugaison avec élimination urinaire des métabolites. Approximativement 10% du paracétamol est oxydé par la voie du cytochrome 2E1 qui aboutit à du NAPQI, métabolite oxydant rapidement contrecarré par le glutathion. Lors d’un surdosage en paracétamol, la production exacerbée de NAPQI est responsable de la toxicité hépatique. Un pourcentage quasiment négligeable du paracétamol est éliminé sous forme inchangé dans les urines.
Le paracétamol est un médicament qui a basé son succès sur son efficacité et sa sécurité d’emploi. Le paracétamol diminue la douleur contre placebo, ouf. Le nombre de patient à traiter avec 1g de paracétamol pour diminuer la douleur de 50% est d’environ 3,8 (NNT) : bon médicament ! Ensuite le paracétamol se révèle à l’usage être d’une excellente sécurité d’emploi pour peu que le patient soit éduqué en automédication et que le médecin prescripteur fasse preuve d’un minimum de vigilance : pas plus d’1g toutes les six heures.
Le paracétamol est sûr à l’usage, même dans des population difficiles : les patients âgés peuvent recevoir 3g par jour sans difficultés, les femmes enceintes et allaitantes n’exposent pas leur enfant à un risque particulier, les insuffisants rénaux ne craignent rien en limitant la dose à 3g/jour. Les patients souffrant de pathologies hépatiques bénignes peuvent utiliser de façon sûre le paracétamol. Les alcooliques qui constituent une population à risque de surdosage (insuffisance hépatique potentielle, augmentation du CYP 2E1) peuvent l’utiliser également (lorsque l’on a écarté les situations de dégradation de la fonction hépatique). Les interactions médicamenteuses sont très limitées (un peu de vigilance avec les AVK tout de même, comme avec tout médicament associé aux AVK). Bref la panacée !
Nous l’utilisons donc largement. Mais je m’interroge quant au service rendu au patient dans le contexte de la chirurgie lourde qui nécessitera de toute façon l’administration de morphine via une PCA ? et quel coût engendré : produit, lignes de perfusion, temps à manipuler les lignes…
Belle coïncidence, le BJA sort ce mois ci Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review. Maund E, McDaid C, Rice S, Wright K, Jenkins B, Woolacott N. Br J Anaesth. 2011 Mar;106(3):292-7. La méthodologie de l’étude est nouvelle à mes yeux, il s’agit d’une MCT : mixed traitment comparison. En gros les auteurs essayent de comparer via des études différentes des médicaments qui n’ont pas été comparés entre eux. On peut tout de suite s’interroger sur le niveau de preuves de ce type d’études… à rapprocher des méta-analyses…
Toujours est-il que l’on y apprend que le paracétamol diminue certes de 20% la consommation de morphine mais que ceci n’évite pas les effets indésirables de la morphine, déception non ? Cette étude ne permet pas d’évaluer l’amélioration de l’analgésie fournie en administrant du paracétamol ou des AINS en sus de la PCA morphine. Ceci dit je me pose de plus en plus la question de la nécessité de la multiplication des analgésiques que l’on administre ensemble sans trop savoir ce que donne le cocktail, le multimodal pourquoi pas mais non à la myriade d’antalgiques sans comprendre…
Pistes pour la réflexion et l’action :
- Proposer le paracétamol en fonction d’un protocole d’évaluation de la douleur et éduquer les équipes quant à la possibilité de ne pas utiliser systématiquement le paracétamol injectable pour diminuer les coûts (1 euro 50 le flacon chez nous) et les manipulations des lignes de perfusions (surtout les voies centrales)
- Passer per os le plus vite possible +++
- Anticiper l’analgésie et l’hyperalgésie en pré et perop
- Simplifier les prescriptions d’analgésiques post-opératoires, remettre au goût du jour des protocoles simples communs ?
- Anticiper, proposer et utiliser plus de techniques d’analgésie loco-régionale
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15 réponses sur « Focus sur le paracétamol »
Juste fan de cet article de très grande qualité! Merci!
[…] This post was mentioned on Twitter by Thomas Nenninger, nfkb. nfkb said: Mal à la tête ? Focus sur le paracétamol | nfkb0's blog (ecn, nutrition, sport et autres choses*) – http://goo.gl/9i1yT […]
Je me suis toujours demandé si on était crédible dans le cadre de l’urgence à dire aux patients qu’on leur administrait un antalgique (notamment IV) à base de paracetamol, sur une « urgence douloureuse ». Ou du moins de respecter la séquence palier 1, et si la douleur n’est pas soulagée, palier 2 voire 3 direct.
En gros, si on ne bénéficiait pas juste de l’effet placebo alors qu’on posait un cataplasme sur une jambe de bois (ok les pratiques évoluent mais souvent c’est encore comme ça).
Les EVA sont là pour ça mais sont elles fiables chez tout le monde. Il y a des gens qui n’osent pas se plaindre. Faut il les « indoloriser » sans leur demander leur avis ?
Je ne dis pas que c’est un médicament obsolète, je ne le pense pas, mais je rejoins la déception en apprenant la faible efficacité sur la réduction d’utilisation de morphine associée.
le respect des paliers a surtout du sens dans les douleurs chroniques.
En urgence et/ou avec les douleurs aiguës, c’est comme avec les anti-infectieux : on tape fort et on adapte.
Le paracétamol est un excellent médicament. Il gagne contre placebo dans les douleurs modérées. Simplement je pense que nous l’utilisons trop systématiquement et moi j’aimerais bien récupérer les 6 euros par jour de traitement pour prescrire des parentérales de qualité supérieure et/ou un peu plus de glutamine.
quant à l’analgésie systématique elle dépend évidemment du contexte et l’espace ici est trop court pour discuter du caractère multifactoriel de la douleur. Chez les patients qui se plaignent peu nous nous servons tout simplement des constantes vitales pour jauger leur « état adrénergique ». Bientôt le monitoring de l’intervalle R-R sur l’ECG nous donnera un indice objectif d’aide à la décision.
De nouvelles études montrent qu’une dose de 2g en première dose pour le post op était beaucoup plus efficace et sans aucun effet indésirable clinique ou biologique constaté.
Maintenant c’est pas quelque chose que je ferais nécessairement, mais je trouve ça cool que ça existe et que ça se fait, si ça permet au patients d’avoir moins mal et d’avoir une épargne morphinique sans effets indésirables.
Bonjour,
je pense même que ça fait un moment que des travaux l’ont montré. Néanmoins sur la chirurgie mineure, avec la dexa, le paracétamol, l’AINS on arrive à un bon niveau de satisfaction déjà, alors il faudrait vraiment une amélioration drastique du service rendu pour changer la pratique. J’ai du mal à voir l’intérêt. D’autant plus que je mets souvent en prémédication le gramme de paracétamol pour les chirurgies mineures courtes, donc je suis déjà très bas en coût.
Probablement trop et mal utilisé, mal associé. Des perfusions IV qui s’éternisent pendant plus de deux heures…
Beaucoup de résistance au changement rencontrée dans la pratique de la prise PO en préop immédiat. Comme tu le dis, probablement beaucoup d’argent dépensé pour pas grand chose.
Et quand je n’en prescris pas au bénéfice d’autres antalgiques (AINS surtout), les IADE me regardent parfois comme si j’étais le Dr Mengele et poussent des cris d’orfraie…
et oui on passe pour des criminels lorsqu’on ne prescrit pas systématiquement du paracétamol… comme c’est extrêmement fatiguant de se battre contre vents et marées, je commence ma croisade en relayant au maximum per os… on verra la suite plus tard
par ailleurs je n’ai pas traité de ça dans le billet mais un de mes internes m’expliquait qu’il existait des hypotensions induites… tu as déjà rencontré ce genre de choses ?
C’est à la limite de la légende urbaine 😛
Ça a été rapporté chez des patients fébriles instables de réanimation, l’hypothèse est une diminution de la précharge secondaire à la vasoplégie et une diminution de l’ordre de 10% du débit cardiaque. Pertinence pour un patient ASA I-II ?
En allergologie, de manière régulière, se pose la question de sa consommation pendant la grossesse et pendant les premiers mois de vie (cf http://www.allergique.org/article3323.html par exemple), mais pas de problème avec la consommation ponctuelle hein 🙂
Intéressant. Alors bon ou pas bon? efficace jusqu’à quel niveau? Pourquoi donné un anti-douleur alors qu’on n’a pas mal? Et quand on a mal, on obtient la réponse se n’est rien, pas besoin de prendre en charge ou on ne sait pas pourquoi la douleur est là et donc on ne traite pas.
Le paracétamol en gélule était super. Une seule a suffi pour soulager une belle crise du cartilage. Mais bon au bout de plus une décennie, l’efficacité est moindre ou l’arthrose trop avancé. Dommage, mais bon.
Bonne soirée
oui c’est un bon médicament : efficace, pas cher, peu d’effets indésirables
la douleur est individuelle, à adapter au cas par cas donc
à bientot
Petit commentaire complémentaire : son efficacité est liée au pic plasmatique … Plus il est élevé, plus le passage central est important, plus il est efficace (c’est la chanson que me chante un spécialiste du sujet).
Pertinent en postop ? Dans les temps anciens, on utilisait la morphine en monothérapie pour le postop. Est venu le temps de l’analgésie multi-modale … un peu de ceci, un peu de ça … comme le picon-vin blanc : au plus on en met, au meilleur c’est ?
Puis est venle temps de l’analgésie loco-régionale … et nous avons gardé la multi-modale.
Il est sûrement temps de faire le « ménage ». Une analgésie efficace par voie péridurale nécessite-t-elle du paracétamol en sus ? Je ne le pense pas. Par contre une PCA-IV à la morphine ? J’ai le sentiment que là c’est plus utile (même si ça ne diminue pas les effets secondaires) : nos patients qui ont mal apprécient une diminution de la douleur de 20 % (modeste).
Au total, la roue du temps n’arrête pas : nous continuerons de brûler ce que nous avons adoré …. Essayons d’arrêter le balancier au milieu 🙂 Didier Delbrouck anesthésiste presque croulant
[…] et simples pourquoi pas donner le paracétamol et/ou les AINS en prémé en stomato simple par ex (meilleur coût et bénéfice pour le patient) […]
[…] qu’il y a une analgésie loco-régionale. Ensuite je prescris du paracétamol en IV (même si les preuves sont minces, le rapport bénéfice/risque me parait bon). Si le patient bénéficie du contrôle de […]