Canadian Journal of Anaesthesia

, Volume 44, Issue 4, pp 377–384

Transdermal fentanyl system plusim ketorolac for the treatment of postoperative pain

  • Douglas J. Reinhart
  • Michael E. Goldberg
  • Jonathan V. Roth
  • Rita Dua
  • Igal Nevo
  • Kevin W. Klein
  • Marc Torjman
  • Denis Vekeman
Reports of Investigation

Abstract

Purpose

To assess the safety and efficacy of transoermal fentanyl plus im ketorolac vs im ketorolac alone in the treatment of postoperative pain.

Methods

Ninety-two patients scheduled for surgery involving moderate to severe postoperative pain were randomized to one of two groups. Group A (n=46) received an active fentanyl patch and group P (n=46) received a placebo patch. Patches remained in place for 24 hr. Each patient received intraoperative ketorolac, 60 mgim. Patients were monitored for 36 hr postoperatively and the groups were analyzed for ketorolac usage, pain scores. vital signs, serum fentanyl concentrations, and adverse events. Intramuscular ketorolac was available on demand.

Results

Group A had lower pain scores at 8, 12, 16 and 24 hr after patch placement (P< 0.05). Group A had lower heart rates, lower respiratory rates and fewer dropouts due to inadequate pain relief (4.3% vs 21.7%, P< 0.05). Group A patients also used less ketorolac than group P patients (P< 0.05). The incidence of pruntus was higher in group A patients (19%vs 2%, P< 0.05), while the incidence of nausea and vomiting was not different between the two groups. Transdermal fentanyl was adequate “stand-alone” analgesia in only 23.8% of group A patients while 93.7% of the remaining group A patients receiving a combination of transdermal fentanyl and ketorolac had adequate pain relief.

Conclusion

The transdermal fentanyl delivery system plus ketorolacim was more effective in controlling postoperative pain than ketorolacim alone. The two treatment modalities were comparable in safety with no difference in serious adverse events.

Résumé

Objectif

Évaluer en rapport avec le traitement de la douleur postopératoire la sécurité et l’efficacité du fentanyl transdermique associé au kétorolac avec celles du kétorolac seul.

Méthodes

Quatre-vingt-douze patients programmés pour une chirurgie comportant des douleurs postopératoires modérées à graves étaient répartis aléatoirement entre deux groupes. Le groupe A (n = 46) recevait un timbre autocollant au fentanyl et le groupe P (n=46) un timbre placebo. Les timbres demeuraient en place pendant 24 h. Chaque patient recevait 60 mg de kétorolacim pendant l’intervention. Les patients étaient gardés sous surveillance pendant 36 h après l’intervention et la dose de kétorolac utilisée, les scores de douleur, les signes vitaux, les concentrations de fentanyl et les incidents indésirables étaient notés. Du kétorolac était administréim sur demande.

Résultats

Les patients du groupe A présentaient les scores de douleur les plus bas à 8, 12. 16 et 24 h après l’application du timbre (P< 0.05). Les patients du groupe A avaient la fréquence cardiaque et respiratoire la plus lente et le moins de décrochage par insatisfaction (4,3%vs 21,7%$, P< 0,05). Les patients du groupe A ont aussi utilisé moins de kétorolac que ceux du groupe P (P< 0.05). Lincidence de prurit était plus élevée chez les patients du groupe A (19% vs 2%. (P< 0.05), alors que l’incidence des nausées et des vomissements était la même dans les deux groupes. Le fentanyl transdermique n’était suffisant comme analgésique unique que dans seulement 23,8% des patients du groupe A; 93.7% des autres patients du groupe A qui avaient reçu une combinaison de fentanyl transdermique et de kétorolac étaient suffisamment soulagés.

Conclusions

L’administration transdermique de fentanyl associé au kétorolacim a été plus efficace pour soulager la douleur que le kétorolacim seul. Sous l’aspect de la sécunté et des incidents indésirables, les deux méthodes étaient comparables.

References

  1. 1.
    Bailey PL, Stanley TH. Package inserts and other dosage guidelines are especially useful with new analgesics and new analgesic delivery systems (Editorial). Anesth Analg 1992; 75: 873–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Sandier A. Transdermal fentanyl: acute analgesic clinical studies. J Pain Symptom Manage 1992; 7: S27–35.CrossRefGoogle Scholar
  3. 3.
    Wright C. Medical Officer Review, NDA #19813, Alza Corp. TTS Fentanyl (transdermal therapeutic system), Volume 2, Pharmacokinetics & Pharmacodynamics, June 1990, obtained via Freedom of Information Act of Congress.Google Scholar
  4. 4.
    Wright C. Medical Officer Review, NDA #19813, Alza Corp. TTS Fentanyl (transdermal therapeutic system), Volume 4, Safety, May 1990, obtained via Freedom of Information Act of Congress.Google Scholar
  5. 5.
    Duragesic (fentanyl transdermal system) Package Insert, January 1996.Google Scholar
  6. 6.
    Miguel R, Kreitzer JM, Reinbart DJ, et al. Postoperative pain control with a new transdermal fentanyl delivery system. A multicenter trial. Anesthesiology 1995; 83: 470–7.Google Scholar
  7. 7.
    Fiset P, Cohane C, Browne S, Brand SC, Shafer SL. Biopharmaceutics of a new transdermal fentanyl device. Anesthesiology 1995; 83: 459–69.PubMedCrossRefGoogle Scholar
  8. 8.
    Sandier AN, Baxter AD, Katz J, et al. A double blind, placebo-controlled trial of transdermal fentanyl after abdominal hysterectomy. Anesthesiology 1994; 81: 1169–80.CrossRefGoogle Scholar
  9. 9.
    Stanski DR. Different modes of administrationiv vs nasalvs patch. American Society of Anesthesiologists Annual Review Course Lectures, San Fransisco, Calif, 1994: #252, 1–3.Google Scholar
  10. 10.
    Michiels M, Hendricks R, Heykants J. A sensitive radioimmunoassay for fentanyl. Plasma levels in dogs and man. Eur J Clin Pharmacol 1977; 12: 153–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Schüttler J, White PF. Optimization of the radioimmunoassay for measuring fentanyl and alfentanil in human serum. Anesthesiology 1984; 61: 315–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Caplan RA, Ready LB, Oden RV, Matsen FA III, Nessly ML, Olsson GL. Transdermal fentanyl for postoperative pain management. A double-blind placebo study. JAMA 1989; 261: 1036–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Latasch L, Lüders S. Transdermal fentanyl against post-operative pain. Acta Anaesthesiol Belg 1989; 40: 113–8.PubMedGoogle Scholar
  14. 14.
    Holley FO, van Steennis C. Postoperative analgesia with fentanyl: pharmacokinetics and pharmacodynamics of constant-rateiv and transdermal delivery. Br J Anaesth 1988; 60: 608–13.PubMedCrossRefGoogle Scholar
  15. 15.
    Gourlay GK, Kowalski SR, Plummer JL, Cherry DA, Gaukroger P, Cousins MJ. The transdermal administration of fentanyl in the treatment of postoperative pain: pharmacokinetics and pharmacodynamic effects. Pain 1989; 37: 193–202.PubMedCrossRefGoogle Scholar
  16. 16.
    Gourlay GK, Kowalski SR, Plummer JL, et al. The efficacy of transdermal fentanyl in the treatment of postoperative pain: a double-blind comparison of fentanyl and placebo systems. Pain 1990; 40: 21–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Duthie DJR, Rowbotham DJ, Wyld R, Henderson PD, Nimmo WS. Plasma fentanyl concentrations during transdermal delivery of fentanyl to surgical patients. Br J Anaesth 1988; 60: 614–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Rowbotham DJ, Wyld R, Peacock JE, Duthie DJR, Nimmo WS. Transdermal fentanyl for the relief of pain after upper abdominal surgery. Br J Anaesth 1989; 63: 56–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Lehmann KA, Einnolf C, Eberlein H-J, Nagel R. Transdermal fentanyl for the treatment of pain after major urological operations. A randomized doubleblind comparison with placebo using intravenous patient-controlled analgesia. Eur J Clin Pharmacol 1991; 41: 17–21.PubMedCrossRefGoogle Scholar
  20. 20.
    Murat I, Levron J-C, Berg A, Saint-Maurice C. Effects of fentanyl on baroreceptor reflex control of heart rate in newborn infants. Anesthesiology 1988; 68: 717–22.PubMedCrossRefGoogle Scholar
  21. 21.
    Gourlay GK, Kowalski SR, Plummer JL, Cousins MJ, Armstrong PJ. Fentanyl blood concentration — analgesic response relationship in the treatment of postoperative pain. Anesth Analg 1988; 67: 329–37.PubMedCrossRefGoogle Scholar
  22. 22.
    Power I, Noble DW, Douglas E, Spence AA. Comparison of i.m. ketorolac tromethamine and morphine sulfate for pain relief after cholecystectomy. Br J Anaesth 1990; 65: 448–55.PubMedCrossRefGoogle Scholar
  23. 23.
    Powell H, Smallman JMB, Morgan M. Comparison of intramuscular ketorolac and morphine in pain control after laparotomy. Anaesthesia 1990; 45: 538–42.PubMedCrossRefGoogle Scholar
  24. 24.
    O’Hara DA, Fragen RJ, Kinzer M, Pemberton D. Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. Clin Pharmacol Ther 1987; 41: 556–61.PubMedGoogle Scholar
  25. 25.
    Abmmowicz M. Ketorolac tromethamine. Med Lett Drugs Ther 1990; 32: 79–81.Google Scholar
  26. 26.
    Ready LB, Brown CR, Stahlgren LH, et al. Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain. Anesthesiology 1994; 80: 1277–86.PubMedCrossRefGoogle Scholar
  27. 27.
    Yum SI. Transdermal therapeutic systems and rate controlled drug delivery. Med Prog Technol 1989; 15: 47–52.PubMedGoogle Scholar
  28. 28.
    Plezia PM, Kramer TH, Linford J, Hameroff SR. Transdermal fentanyl: pharamacokinetics and preliminary clinical evaluation. Pharmacotherapy 1989; 9: 2–9.PubMedGoogle Scholar

Copyright information

© Canadian Anesthesiologists 1997

Authors and Affiliations

  • Douglas J. Reinhart
    • 1
    • 5
  • Michael E. Goldberg
    • 2
    • 5
  • Jonathan V. Roth
    • 3
    • 5
  • Rita Dua
    • 3
    • 5
  • Igal Nevo
    • 3
    • 5
  • Kevin W. Klein
    • 4
    • 5
  • Marc Torjman
    • 4
    • 5
  • Denis Vekeman
    • 2
    • 5
  1. 1.Department of AnesthesiologyUniversity of UtahUSA
  2. 2.University of Medicine and Dentistry of New JerseyUSA
  3. 3.Temple University School of MedicineUSA
  4. 4.Southwestern Med CtrUniversity of TexasDallasUSA
  5. 5.Jefferson Medical CollegeUSA
  6. 6.Department of AnesthesiologyMcKay-Dee HospitalOgden

Personalised recommendations