Intramuscular tramadol increases gastric pH during anesthesia

  • Kouichiro Minami
  • Junichi Ogata
  • Takafumi Horishita
  • Munehiro Shiraishi
  • Takashi Okamoto
  • Takeyoshi Sata
  • Akio Shigematsu
General Anesthesia



Tramadol, [(1RS, 2RS)-2-dimethylamino) methyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride], is an analgesic in clinical use. It has been reported that tramadol inhibits muscarinic type 3 receptor function, which primarily mediates smooth muscle contraction and glandular secretion. We investigated the effects of tramadol on the pH of gastric juices during anesthesia to determine whether tramadol inhibits secretion from the gastric glands.


ASA physical status I or II adult patients (n = 30) presenting for major elective orthopedic surgery of the upper extremities or mastectomy were enrolled. Patients were randomly assigned to receive treatment with tramadol (n = 10), famotidine (n = 10), or saline (n = 10). General anesthesia was then induced using propofol, vecuronium bromide, and fentanyl. After inducing anesthesia, the gastric pH was measured using pH test paper and, then, 100 mg tramadol, 20 mg famotidine, or saline were injected into the deltoid muscle. Three hours after starting the operation, gastric juice was again aspirated and its gastric pH measured.


There were no differences in the pH before anesthesia between the three groups. By contrast, gastric pH was increased in the tramadol group by the same amount as it was in the famotidine group three hours after administering the drugs. Gastric pH of the saline, famotidine, and tramadol groups was 2.6 ± 2.5, 6.3 ± 2.0, and 6.4 ± 0.8, respectively.


These results suggest that tramadol inhibits the secretion of gastric acid.


Tramadol Famotidine Gastric Gland Vecuronium Bromide Adrenal Medullary Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

L’administration intramusculaire du tramadol augmente le pH gastrique pendant l’anesthésie



Le tramadol, [(1RS, 2RS)-2-diméthylamino) méthyl-1-(3-méthoxyphényl)-cyclohexanol hydrochloride], est un analgésique d’usage clinique. On a montré que le tramadol inhibe la fonction des récepteurs muscariniques de type 3 dont le principal rôle est de servir de médiateur à la contraction des muscles lisses et à la sécrétion glandulaire. Nous avons examiné les effets du tramadol sur le pH des sucs gastriques pendant l’anesthésie afin de déterminer si le tramadol inhibe la sécrétion des glandes gastriques.


Des patients adultes d’état physique ASA I et II (n = 30) admis pour une intervention orthopédique majeure réglée aux membres supérieurs ou pour une mastectomie ont participé à l’étude. Ils ont été randomisés et ont reçu du tramadol (n = 1 0), de la famotidine (n = 10) ou une solution saline (n = 1 0). L’anesthésie générale a été induite avec du propofol, du bromure de vécuronium et du fentanyl. Après l’induction, le pH gastrique a été mesuré avec un papier indicateur de pH et, ensuite, 100 mg tramadol, 20 mg de famotidine ou une solution saline ont été injectés dans le muscle deltoïde. Trois heures après le début de l’opération, les sucs gastriques ont été aspirés et leur pH mesuré.


Aucune différence de pH n’a été notée avant l’opération et, ce, chez les patients des trois groupes. Par contre, le pH gastrique était plus élevé dans le groupe sous tramadol, de la même quantité qu’il l’a été dans le groupe sous famotidine trois heures après l’administration des médicaments. Le pH gastrique en présence de solution saline, de famotidine et de tramadol a été de 2,6 ± 2,5; 6,3 ± 2,0 et 6,4 ± 0,8 respectivement.


Ces résultats indiquent que le tramadol inhibe la sécrétion d’acide gastrique.


  1. 1.
    Katz WA. Pharmacology and clinical experience with tramadol in osteoarthritis. Drugs 1996; 52(Suppl 3): 39–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Wilder-Smith CH, Bettiga A. The analgesic tramadol has minimal effect on gastrointestinal motor function. Br J Clin Pharmacol 1997; 43: 71–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Sagata K, Minami K, Yanagihara N, et al. Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells. Anesth Analg 2002; 94: 901–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Shiga Y, Minami K, Shiraishi M, et al. The inhibitory effects of tramadol on muscarinic receptor-induced responses in Xenopus oocytes expressing cloned M3 receptors. Anesth Analg 2002; 95: 1269–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Lefkowitz RJ, Hoffman BB, Taylor P. Neurohumoral transmission: the autonomic and somatic motor nervous systems.In: Gilman AG, Rall TW, Nies AS, Taylor P (Eds). Goodman and Gilman’s The pharmacological basis of Therapeutics, 8th ed. New York: Pergamon Press; 1990: 84–121.Google Scholar
  6. 6.
    Pfeiffer A, Kromer W, Friemann J, et al. Muscarinic receptors in gastric mucosa are increased in peptic ulcer disease. Gut 1995; 36: 813–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Lintz W, Beier H, Gerloff J. Bioavailability of tramadol after i.m. injection in comparison to i.v. infusion. Int J Clin Pharmacol Ther 1999; 37: 175–83.PubMedGoogle Scholar
  8. 8.
    Noguchi J, Yamamura H, Inada Y, et al. A doubleblind evaluation of famotidine for pre-anesthetic intramuscular administration — its effects on volume and pH of gastric juice (Japanese). Masui 1987; 36: 592–603.PubMedGoogle Scholar
  9. 9.
    Shiraishi M, Minami K, Uezono Y, Yanagihara N, Shigematsu A. Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing clonedM1 receptors. J Pharmacol Exp Ther 2001; 299: 255–60.PubMedGoogle Scholar
  10. 10.
    Guyton AC. Secretory functions of the alimentary tract.In: Guyton AC (Ed.). Textbook of Medical Physiology, 8th ed. Philadelphia: W.B. Saunders; 1991: 709–25.Google Scholar
  11. 11.
    Zeidler H. Epidemiology of NSAID-induced gastropathy. Clin Rheumatol 1991; 10: 369–73.PubMedCrossRefGoogle Scholar
  12. 12.
    Wilder-Smith CH, Hill L, Wilkins J, Denny L. Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery. Anesthesiology 1999; 91: 639–47.PubMedCrossRefGoogle Scholar
  13. 13.
    Crighton IM, Martin PH, Hobbs GJ, Cobby TF, Fletcher AJ, Stewart PG. A comparison of the effects of intravenous tramadol, codeine, and morphine on gastric emptying in human volunteers. Anesth Analg 1998; 87: 445–9.PubMedCrossRefGoogle Scholar

Copyright information

© Canadian Anesthesiologists 2004

Authors and Affiliations

  • Kouichiro Minami
    • 1
  • Junichi Ogata
    • 1
  • Takafumi Horishita
    • 1
  • Munehiro Shiraishi
    • 1
  • Takashi Okamoto
    • 1
  • Takeyoshi Sata
    • 1
  • Akio Shigematsu
    • 1
  1. 1.Department of Anesthesiology, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan

Personalised recommendations