Justified antalgiques.pptx

Dr Arnaud Depil Duval – Urgences Paris Saint Joseph
LES
ANTALGIQUES
Dr Arnaud Depil Duval - Urgences Paris Saint Joseph

Avertissement
•Au cours de cette présentation,
•Les phrases « Moi je… » et
« D’habitude on… »
•Sont strictement prohibées…

Les bases

Rappel
• Ceci n’est pas un antalgique…

• Crée en 1986
• Pour la prise en charge
des douleurs
chroniques
• Changement de paliers
tous les 24 heures
Classification
OMS

Classification
Lussier - Beaulieu
• Analgésie multimodale
• Classes thérapeutiques

Comment ça marche ?

Synergies

Synergie
• Comparaison des médianes de la
dose efficace (ED50)
• A : Additivité
• S : Synergie
• I : infra-additivité
Dose
médicament
1
Dose médicament 2

Epargne morphinique
<20%
Pas de diminution des
effets secondaires
Paracétamol et morphine
Elia, Nadia, et al. « Does Multimodal Analgesia with Acetaminophen, Nonsteroidal Antiinflammatory Drugs, or Selective
Cyclooxygenase-2 Inhibitors and Patient-Controlled Analgesia Morphine Offer Advantages over Morphine Alone? Meta-Analyses of
Randomized Trials ». Anesthesiology, vol. 103, no 6, décembre 2005, p. 1296-304, https://doi.org/10.1097/00000542-200512000-
00025.

• Epargne morphinique jusqu’à 50%
AINS et Morphine
• Maund, E., et al. « 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 ». British
Journal of Anaesthesia, vol. 106, no 3, mars 2011, p. 292-97, https://doi.org/10.1093/bja/aeq406.

• 32 études
• Court terme
• A peine plus efficaces que le
placebo
AINS et lombalgies
van der Gaag WH, Roelofs PDDM, Enthoven WTM, van Tulder MW, Koes BW. Non-steroidal anti-inflammatory
drugs for acute low back pain. Cochrane Database of Systematic Reviews 2020, Issue 4. Art. No.: CD013581. DOI:
10.1002/14651858.CD013581

Tramadol

Effets bénéfiques
• Une alternative aux opioides
• Lu L, Harnett M, Reines SA. IV tramadol: A novel option for
US patients with acute pain-A review of its
pharmacokinetics, abuse potential and clinical safety record.
J Opioid Manag. 2020 Jul/Aug;16(4):297-306. doi:
10.5055/jom.2020.0584. PMID: 32885838.
• Douleurs neuropathiques : mieux que les
opioïdes?
• Non…
• Duehmke RM, Hollingshead J, Cornblath DR. Tramadol
for neuropathic pain. Cochrane Database of Systematic
Reviews 2006, Issue 3. Art. No.: CD003726. DOI:
10.1002/14651858.CD003726.pub3

Effets secondaires
• Patients âgés
• Hypoglycémie : 2x>codéine
• Fournier J, Azoulay L, Yin H, Montastruc J, Suissa S. Tramadol Use and
the Risk of Hospitalization for Hypoglycemia in Patients With
Noncancer Pain. JAMA Intern Med. 2015;175(2):186-193.
doi:10.1001/jamainternmed.2014.6512
• Augmentation du risque de fractures
• Hirst, A., Knight, C., Hirst, M., Dunlop, W. & Akehurst, R. Tramadol and
the risk of fracture in an elderly female population: a cost utility
assessment with comparison to transdermal buprenorphine. Eur J
Health Econ 17, 217–227 (2016)
• Costa-Dias, M. J. et al. Medication fall risk in old hospitalized patients:
a retrospective study. Nurse Educ Today 34, 171–176 (2014)
• Seuil épileptogène abaissé
• Syndrôme sérotoninergique :
• Majoré si association aux IMAO et aux ISRS

Dépendance ?
• OSIAP 2017 (Ordonnances
Suspectes Indicateurs d’Abus
Possible)
• ANSM État des lieux de la consommation des
antalgiques opioïdes et leurs usages
problématiques 2019 :
• (...) Plus de 50% des syndromes (ou
signes) de sevrage au tramadol concernent
des prises à doses thérapeutiques, parfois
pendant une période très courte
(inférieure à une semaine).»
• Un risque à prendre en compte

Au moins un intérêt?...
• 62mg de tramadol pour 2 minutes…
• Bar-Or, D., Salottolo, K. M., Orlando, A., Winkler, J. V. &
Tramadol ODT Study Group. A randomized double-blind,
placebo-controlled multicenter study to evaluate the efficacy
and safety of two doses of the tramadol orally disintegrating
tablet for the treatment of premature ejaculation within less
than 2 minutes. Eur. Urol. 61, 736–743 (2012).

• Une seule étude en médecine
d’urgence
• Pas supérieur au placebo
• Uniquement post-op chirurgie
digestive
Nefopam
Moustafa F, Liotier J, Mathevon T, et al
Usefulness of nefopam in treating pain of severe uncomplicated renal colics in adults admitted to
emergency units: a randomised double-blind controlled trial. The ‘INCoNU’ study
Emergency Medicine Journal 2013;30:143-148.

Nefopam per-os
Aymard G, Warot D, Démolis P, Giudicelli JF, Lechat
P, Le Guern ME, Alquier C, Diquet B. Comparative
pharmacokinetics and pharmacodynamics of
intravenous and oral nefopam in healthy volunteers.
Pharmacol Toxicol. 2003 Jun;92(6):279-86. doi:
10.1034/j.1600-0773.2003.920605.x. PMID:
12787260.

Oui mais ça marche
• Naloxone diminue « l’efficacité »
du placebo
• Libération d’opioïdes endogènes
• Majoration des opioïdes
endogènes dans le LCR

Un nouveau traitement dans la sciatique

Paracétamol

• Réduction de la clairance du
paracétamol
• Dose récommandée : 3g/24h voire
500mg /6h
Paracetamol et gériatrie
What dose of paracetamol for older people? Drug Ther
Bull. 2018 Jun;56(6):69-72. doi: 10.1136/dtb.2018.6.0636.
PMID: 29903753.
Divoll M, Ameer B, Abernethy DR, Greenblatt DJ. Age does
not alter acetaminophen absorption. J Am Geriatr Soc.
1982 Apr;30(4):240-4. doi: 10.1111/j.1532-
5415.1982.tb07093.x. PMID: 7069091.

• 14 études
• En chirurgie
• Economie : 43.000€/an
IV ou per-os
Mallama M, Valencia A, Rijs K, Rietdijk WJR, Klimek
M, Calvache JA. A systematic review and trial
sequential analysis of intravenous vs. oral peri-
operative paracetamol. Anaesthesia. 2021
Feb;76(2):270-276. doi: 10.1111/anae.15163. Epub
2020 Jun 18. PMID: 32557588; PMCID:
PMC7818191.

• Fièvre chez l’enfant
• Aucune preuve de l’antalgie dans
les études (échec)
• Pic à 40 min
• Réservée si per-os impossible
Afssaps. Prise en charge médicamenteuse de la douleur aiguë et chronique
chez l’enfant : recommandations pour la pratique clinique
Intra-rectal vs per-os
Goldstein LH, Berlin M, Berkovitch M, Kozer E. Effectiveness of oral
vs rectal acetaminophen: a meta-analysis. Arch Pediatr Adolesc Med.
2008 Nov;162(11):1042-6. doi: 10.1001/archpedi.162.11.1042. PMID:
18981352.
https://pediadol.org/halte-aux-
suppositoires/#:~:text=Apr%C3%A8s%2035%20mg%2Fkg%20par,sont%20b
asses%2C%20retard%C3%A9es%20et%20impr%C3%A9visibles.

Diazépam / Midazolam

• Efficacité équivalente au placebo
Diazépam et lombalgies
Friedman BW, Irizarry E, Solorzano C, Khankel N, Zapata
J, Zias E, Gallagher EJ. Diazepam Is No Better Than
Placebo When Added to Naproxen for Acute Low Back
Pain. Ann Emerg Med. 2017 Aug;70(2):169-176.e1. doi:
10.1016/j.annemergmed.2016.10.002. Epub 2017 Feb 7.
PMID: 28187918; PMCID: PMC5517351.

• Mieux toléré que le midazolam
• Propofol : moins d’apnée et moins d’agitation
• Demi-vie propofol 30 min / Diazepam 32 à 47
heures…
Diazépam et sédation
1. Wright SW, Chudnofsky CR, Dronen SC, Kothari R, Birrer P, Blanton DM, Bruner A. Comparison of midazolam and diazepam for
conscious sedation in the emergency department. Ann Emerg Med. 1993 Feb;22(2):201-5. doi: 10.1016/s0196-0644(05)80203-3.
PMID: 8427432.
2. Afzalimoghaddam M, Khademi MF, Mirfazaelian H, Payandemehr P, Karimialavijeh E, Jalali A. Comparing Diazepam Plus Fentanyl
With Midazolam Plus Fentanyl in the Moderate Procedural Sedation of Anterior Shoulder Dislocations: A Randomized Clinical Trial.
J Emerg Med. 2021 Jan;60(1):1-7. doi: 10.1016/j.jemermed.2020.09.030. Epub 2020 Oct 21. PMID: 33097351.
3. Holas A, Faulborn J. Propofol versus Diazepam. Sedierung bei ophthalmologischen Operationen in Lokalanästhesie [Propofol
versus diazepam. Sedation in ophthalmologic surgery under local anesthesia]. Anaesthesist. 1993 Nov;42(11):766-72. German.
PMID: 8279689.

• Equivalent ; léger avantage propofol
Propofol ou midazolam
1. Hohl CM, Sadatsafavi M, Nosyk B, Anis AH. Safety and clinical effectiveness of midazolam versus propofol for procedural
sedation in the emergency department: a systematic review. Acad Emerg Med. 2008 Jan;15(1):1-8. doi: 10.1111/j.1553-
2712.2007.00022.x. PMID: 18211306.
2. Lameijer H, Sikkema YT, Pol A, Bosch MGE, Beije F, Feenstra R, Bens BWJ, Ter Avest E. Propofol versus midazolam for
procedural sedation in the emergency department: A study on efficacy and safety. Am J Emerg Med. 2017 May;35(5):692-
696. doi: 10.1016/j.ajem.2016.12.075. Epub 2017 Jan 3. PMID: 28073611.
3. Hatamabadi HR, Arhami Dolatabadi A, Derakhshanfar H, Younesian S, Ghaffari Shad E. Propofol Versus Midazolam for
Procedural Sedation of Anterior Shoulder Dislocation in Emergency Department: A Randomized Clinical Trial. Trauma
Mon. 2015 May;20(2):e13530. doi: 10.5812/traumamon.13530. Epub 2015 May 20. PMID: 26290851; PMCID:
PMC4538724.
4. Taylor DM, O'Brien D, Ritchie P, Pasco J, Cameron PA. Propofol versus midazolam/fentanyl for reduction of anterior
shoulder dislocation. Acad Emerg Med. 2005 Jan;12(1):13-9. doi: 10.1197/j.aem.2004.08.039. PMID: 15635132.
5. Nejati A, Moharari RS, Ashraf H, Labaf A, Golshani K. Ketamine/propofol versus midazolam/fentanyl for procedural
sedation and analgesia in the emergency department: a randomized, prospective, double-blind trial. Acad Emerg Med.
2011 Aug;18(8):800-6. doi: 10.1111/j.1553-2712.2011.01133.x. PMID: 21843215.

Sédation procédurale et luxation gléno-
humérale
• Reduction d’épaule : augmentation du
risque de fracture iatrogénique sans
sédation
• Pas plus d’accident sous sédation
Pan X, Yao Y, Yan H, Wang J, Dai L, Qu X, Fang Z, Feng F, Zhou Y. Iatrogenic
fracture during shoulder dislocation reduction: characteristics, management and
outcomes. Eur J Med Res. 2021 Jul 12;26(1):73. doi: 10.1186/s40001-021-00545-
3. PMID: 34247652; PMCID: PMC8274043.
Furuhata R, Kamata Y, Matsumura N, Kono A, Morioka H. Risk factors for failure of
reduction of anterior glenohumeral dislocation without sedation. J Shoulder Elbow
Surg. 2021 Feb;30(2):306-311. doi: 10.1016/j.jse.2020.06.005. Epub 2020 Jun 27.
PMID: 32599286.

Propofol
• Recommandation ACEP 2018

Bibliographie
• Abril, Lorena, et al. « The Relative Efficacy of Seven Skeletal Muscle Relaxants. An Analysis of Data From Randomized Studies ». The Journal of Emergency Medicine, vol.
62, no 4, avril 2022, p. 455-61, https://doi.org/10.1016/j.jemermed.2021.09.025.
• Afzalimoghaddam, Mohammad, et al. « Comparing Diazepam Plus Fentanyl With Midazolam Plus Fentanyl in the Moderate Procedural Sedation of Anterior Shoulder
Dislocations: A Randomized Clinical Trial ». The Journal of Emergency Medicine, vol. 60, no 1, janvier 2021, p. 1-7, https://doi.org/10.1016/j.jemermed.2020.09.030.
• Atkinson, Hartley C., et al. « Pharmacokinetics and Bioavailability of a Fixed-Dose Combination of Ibuprofen and Paracetamol after Intravenous and Oral
Administration ». Clinical Drug Investigation, vol. 35, no 10, octobre 2015, p. 625-32, https://doi.org/10.1007/s40261-015-0320-8.
• Aymard, Guy, et al. « Comparative Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Nefopam in Healthy Volunteers ». Pharmacology & Toxicology, vol.
92, no 6, juin 2003, p. 279-86, https://doi.org/10.1034/j.1600-0773.2003.920605.x.
• Balzer, Nathan, et al. « Low-Dose Ketamine For Acute Pain Control in the Emergency Department: A Systematic Review and Meta-Analysis ». Academic Emergency
Medicine: Official Journal of the Society for Academic Emergency Medicine, vol. 28, no 4, avril 2021, p. 444-54, https://doi.org/10.1111/acem.14159.
• Beaulieu, Pierre, et al. Pharmacology of Pain. International Association for the Study of Pain (IASP), 2010, https://hal-unilim.archives-ouvertes.fr/hal-00661449.
• Divoll, M., et al. « Age Does Not Alter Acetaminophen Absorption ». Journal of the American Geriatrics Society, vol. 30, no 4, avril 1982, p. 240-44,
https://doi.org/10.1111/j.1532-5415.1982.tb07093.x.
• Duehmke, Rudolf Martin, et al. « Tramadol for Neuropathic Pain ». Cochrane Database of Systematic Reviews, édité par The Cochrane Collaboration, John Wiley & Sons,
Ltd, 2006, p. CD003726.pub3, https://doi.org/10.1002/14651858.CD003726.pub3.
• Durrieu, G., et al. « Overview of Adverse Reactions to Nefopam: An Analysis of the French Pharmacovigilance Database ». Fundamental & Clinical Pharmacology, vol. 21,
no 5, octobre 2007, p. 555-58, https://doi.org/10.1111/j.1472-8206.2007.00499.x.
• Elia, Nadia, et al. « Does Multimodal Analgesia with Acetaminophen, Nonsteroidal Antiinflammatory Drugs, or Selective Cyclooxygenase-2 Inhibitors and Patient-
Controlled Analgesia Morphine Offer Advantages over Morphine Alone? Meta-Analyses of Randomized Trials ». Anesthesiology, vol. 103, no 6, décembre 2005, p.
1296-304, https://doi.org/10.1097/00000542-200512000-00025.
• Fournier, Jean-Pascal, et al. « Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain ». JAMA Internal Medicine, vol. 175, no 2,
février 2015, p. 186, https://doi.org/10.1001/jamainternmed.2014.6512.

Bibliographie
• Friedman, Benjamin W., et al. « Diazepam Is No Better Than Placebo When Added to Naproxen for Acute Low Back Pain ». Annals of Emergency Medicine, vol. 70, no 2,
août 2017, p. 169-176.e1, https://doi.org/10.1016/j.annemergmed.2016.10.002.
• Hatamabadi, Hamid Reza, et al. « Propofol Versus Midazolam for Procedural Sedation of Anterior Shoulder Dislocation in Emergency Department: A Randomized Clinical
Trial ». Trauma Monthly, vol. 20, no 2, mai 2015, p. e13530, https://doi.org/10.5812/traumamon.13530.
• Hohl, Corinne Michèle, et al. « Safety and Clinical Effectiveness of Midazolam versus Propofol for Procedural Sedation in the Emergency Department: A Systematic
Review ». Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine, vol. 15, no 1, janvier 2008, p. 1-8,
https://doi.org/10.1111/j.1553-2712.2007.00022.x.
• Ishitsuka, Yoichi, et al. « Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug? » Biological & Pharmaceutical Bulletin, vol. 43, no
2, 2020, p. 195-206, https://doi.org/10.1248/bpb.b19-00722.
• Lameijer, Heleen, et al. « Propofol versus Midazolam for Procedural Sedation in the Emergency Department: A Study on Efficacy and Safety ». The American Journal of
Emergency Medicine, vol. 35, no 5, mai 2017, p. 692-96, https://doi.org/10.1016/j.ajem.2016.12.075.
• Lu, Lucy, et al. « IV Tramadol: A Novel Option for US Patients with Acute Pain-A Review of Its Pharmacokinetics, Abuse Potential and Clinical Safety Record ». Journal of
Opioid Management, vol. 16, no 4, 2020, p. 297-306, https://doi.org/10.5055/jom.2020.0584.
• Machado-Alba, Jorge Enrique, et al. « Use of Tramadol or Other Analgesics in Patients Treated in the Emergency Department as a Risk Factor for Opioid Use ». Pain
Research & Management, vol. 2020, 2020, p. 8847777, https://doi.org/10.1155/2020/8847777.
• Mallama, M., et al. « A Systematic Review and Trial Sequential Analysis of Intravenous vs. Oral Peri-Operative Paracetamol ». Anaesthesia, vol. 76, no 2, février 2021, p.
270-76, https://doi.org/10.1111/anae.15163.
• Mandrekar, Shivani, et al. « Prevalence of Musculoskeletal Chest Pain in the Emergency Department: A Systematic Review and Meta-Analysis ». Scandinavian Journal of
Pain, vol. 21, no 3, juillet 2021, p. 434-44, https://doi.org/10.1515/sjpain-2020-0168.

Bibliographie
• Maund, E., et al. « 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 ». British Journal of Anaesthesia, vol. 106, no 3, mars 2011, p. 292-97, https://doi.org/10.1093/bja/aeq406.
• Moustafa, Farès, et al. « Usefulness of Nefopam in Treating Pain of Severe Uncomplicated Renal Colics in Adults Admitted to Emergency Units: A Randomised Double-
Blind Controlled Trial. The “INCoNU” Study ». Emergency Medicine Journal: EMJ, vol. 30, no 2, février 2013, p. 143-48, https://doi.org/10.1136/emermed-2011-200753.
• Nejati, Amir, et al. « Ketamine/Propofol versus Midazolam/Fentanyl for Procedural Sedation and Analgesia in the Emergency Department: A Randomized, Prospective,
Double-Blind Trial ». Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine, vol. 18, no 8, août 2011, p. 800-06,
https://doi.org/10.1111/j.1553-2712.2011.01133.x.
• Oliveira, Crystian B., et al. « Emergency Department Interventions for Adult Patients with Low Back Pain: A Systematic Review of Randomised Controlled Trials ».
Emergency Medicine Journal: EMJ, vol. 38, no 1, janvier 2021, p. 59-68, https://doi.org/10.1136/emermed-2020-209588.
• Punches, Brittany E., et al. « Emergency Nurse Perceptions of Pain and Opioids in the Emergency Department ». Pain Management Nursing: Official Journal of the
American Society of Pain Management Nurses, vol. 22, no 5, octobre 2021, p. 586-91, https://doi.org/10.1016/j.pmn.2021.05.003.
• Taylor, David McD, et al. « Propofol versus Midazolam/Fentanyl for Reduction of Anterior Shoulder Dislocation ». Academic Emergency Medicine: Official Journal of the
Society for Academic Emergency Medicine, vol. 12, no 1, janvier 2005, p. 13-19, https://doi.org/10.1197/j.aem.2004.08.039.
• « “Weak” Opioid Analgesics. Codeine, Dihydrocodeine and Tramadol: No Less Risky than Morphine ». Prescrire International, vol. 25, no 168, février 2016, p. 45-50.
• « What Dose of Paracetamol for Older People? » Drug and Therapeutics Bulletin, vol. 56, no 6, juin 2018, p. 69-72, https://doi.org/10.1136/dtb.2018.6.0636.
• Xie, Junqing, et al. « Association of Tramadol vs Codeine Prescription Dispensation With Mortality and Other Adverse Clinical Outcomes ». JAMA, vol. 326, no 15, octobre
2021, p. 1504-15, https://doi.org/10.1001/jama.2021.15255.

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