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Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

The Journal of Latvian Academy of Sciences

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Effects of Different Epidural Analgesic Compositions on Postoperative Pain Relief and Systemic Response to Surgery

Iveta Golubovska
  • Hospital of Traumatology and Orthopaedics, Duntes iela 12/22, Rīga, LV-1005, LATVIA
/ Pēteris Studers
  • Hospital of Traumatology and Orthopaedics, Duntes iela 12/22, Rīga, LV-1005, LATVIA
/ Inta Jaunalksne
  • Clinical Immunology Centre, Rīga Stradiñš Hospital, Pilsoñu 13, Rīga, LV-1010, LATVIA
/ Indulis Vanags
  • Department of Anaesthesiology and Reanimatology, Rīga Stradiñš University, Dzirciema iela 16, Rīga, LV-1007, LATVIA
Published Online: 2008-11-29 | DOI: https://doi.org/10.2478/v10046-008-0020-3

Effects of Different Epidural Analgesic Compositions on Postoperative Pain Relief and Systemic Response to Surgery

Despite many achievements during the last decade, postoperative pain remains the dominant complaint after major surgery and has great potential to be influenced by the anaesthesiologist. Reports suggest that short-term effective anaesthesia and analgesia can have long-lasting beneficial effects on recovery from surgery. The aim of our study is to compare the effect of epidural analgesia, using different compositions, including glucocorticoids (methylprednisolone), and habitual composition of bupivacaine-morphine, in regard to analgesic and anti-inflammatory properties. A total of 129 patients participated in the study in four different treatment groups: patients from Group I received glucocorticoid methylprednisolone succinate and long-acting opioid morphine hydrochloride, Group II received local anaesthetic bupivacaine hydrochloride and morphine hydrochloride, Group III received methylprednisolone succinate and short-acting opioid fentanyl, and Group IV received glucocorticoid methylprednisolone succinate. We obtained good analgesic profiles in all groups. However, significantly better results were achieved using the combination of methylprednisolone and morphine. Epidural methylprednisolone in dose 80 mg/24 h is more effective, compared to the conventional local anaesthetics-opioid composition, when administered as a part of multimodal preventive postoperative analgesia after major joint replacement surgery. Epidural methylprednisolone has a reliable anti-inflammatory and immunomodulatory potential. It attenuates profiles of acute inflammatory response markers as Interleukin-6 and C-reactive protein and stress hormone cortisol. The novelty of this study was application of epidural glucocorticoids for acute postoperative pain relief as part of daily perioperative care. By developing studies on anti-inflammatory and immunomodulatory properties of glucocorticoids, we expect to improve patient rehabilitation in the postoperative period.

Dažādu Pēcoperācijas Epidurālo Analgēzijas Kompozīciju Ietekme UZ Atsāpināšanu UN Atbildi Ķirurgiskajam Stresam Pēc Ceļa Endoprotezēšanas Operācijām

Neraugoties uz sasniegumiem pēdējos gados, akūtās pēcoperācijas sāpes ir visbiežākā pacientu sūdzība pēc ķirurgiskas iejaukšanās, taču tās ir potenciāli visvairāk ietekmējamas perioperatīvajā periodā. Mūsu pētījuma mērķis bija salīdzināt epidurālo atsāpināšanu pēc ceļa endoprotezēšanas operācijām, izmantojot dažādas medikamentu kompozīcijas. Mēs salīdzinājām grupas, kuru kompozīcijas ietvēra glikokortikoīdu metilprednizolonu kombinācijās ar dažādiem opioīdiem un bez tiem ar ierasto lokālā anestētiķa bupivakaīna un morfīna kompozīciju un pētījām to ietekmi uz pēcoperācijas atsāpināšanu un neiroendokrīno un imūno atbildi ķirurgiskajam stresam. Pētījumu pabeidza 129 pacienti četrās terapijas grupās. I grupas pacienti epidurāli sañēma glikokortikoīdu metilprednizolona sukcinātu un ilgstošas darbības opioīdu morfīna hidrohlorīdu, II grupas pacienti sañēma lokālo anestētiķi bupivakaīna hidrohlorīdu un morfīna hidrohlorīdu, III grupas pacienti sañēma metilprednizolona sukcinātu un fentanīlu, IV grupas pacienti sañēma metilprednizolona sukcinātu. Atsāpināšana bija ļoti laba visās terapijas grupās, bet metilprednizolona-morfīna grupā mēs ieguvām statistiski ievērojami labākus rezultātus. Epidurālais metilprednizolons devā 80 mg/dn atklājās kā efektīva multimodālās preventīvās atsāpināšanas sastāvdaļa pēc ceļa endoprotezēšanas operācijām. Salīdzinot ar ierasto bupivakaīna-morfīna kompozīciju, ir pierādīts līdzīgs vai pat vēl labāks efekts. Epidurālais metilprednizolons ir arī pierādījis savas imūnmodulējošās un pretiekaisuma īpašības, ietekmējot akūtās pēcoperācijas iekaisīgās fāzes mediatorus - interleikīnu-6 un C-reaktīvo olbaltumu un samazinot stresa hormona kortizola līmeni pēcoperācijas periodā. Šī pētījuma novitāte ir glikokortikoīdu epidurālā izmantošana tieši akūto pēcoperācijas sāpju samazināšanai ikdienas darbā. Attīstot pētījumus par metilprednizolona pretiekaisuma un imūnmodulējošām īpašībām, mēs vēlētos uzlabot pacientu rehabilitāciju pēcoperācijas periodā.

Keywords: glucocorticoids; methylprednisolone; epidural; postoperative analgesia

  • Apfel, C. C., Korttila, K., Abdalla, M., Sessler, D. I., Roewer, N. (2004). A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N. Engl. J. Med., 350, 2441-2451.

  • Barnes, P. (1998). Anti-inflammatory actions of glucocorticoids: Molecular mechanisms. Cli. Sci., 94, 557-572.

  • Bisgaard, T., Klarskov, B., Kehlet, H., Rosenberg, J. (2003). Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy. A randomized double-blind placebo-controlled trial. Ann. Sur., 238, 651-660.

  • Buvanendran, A., Tuman, K. J., McCoy, D. D. (2006). Anesthetic techniques for minimally invasive total knee arthroplasty. J. Knee. Surg., 19, 133-136.

  • Carette, S., Leclaire, R., Marcoux, S., Morin, F., Blaise, G. A., St-Pierre, A., Truchon, R., Parent, F., Levésque, J., Bergeron, V., Montminy, P., Blanchette, C. (1997). Epidural corticosteroid injections for sciatica due to herniated nucleus pulposus. N. Engl. J. Med., 336(23), 1634-1640.

  • Delaney, T. J., Rowlingson, J. C., Carron, H., Butler, A. (1980). Epidural steroid effect on nerves and meninges. Anesth. Analg., 59, 610-614.

  • Di, S., Malcher-Lopes, R., Marcheselli, V. L., Bazan, N. G., Tasker, J. G. (2005). Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and gamma-aminobutyric acid inputs to hypothalamic magnocellular neurons. Endocrinology, 146, 4292-4301.

  • Falkenstein, E., Tillmann, H. C., Christ, M., Feuring, M., Wehling, M. (2000). Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacol. Rev., 52, 513-556.

  • Ferreira, S. H., Cunha, F. Q., Lorenzetti, F. B. (1997). Role of lipocertin-1 in the anti-hyperalgesic action of dexamethasone. Brit. J. Pharm., 121, 883-888.

  • Gilron, I. (2004). Corticosteroids in postoperative pain management: Future research directions for a multifaceted therapy. Acta. Anaesth. Scand., 48, 1221-1222.

  • Glasser, R. S., Knego, R. S., Delashaw, J. B., Fessler, R. G. (1993). The perioperative use of corticosteroids and bupivacaine in the management of lumbar disc disease. J. Neurosurg., 78, 383-387.

  • Golubovska, I., Studers, P., Jaunalksne, I., Vanags, I. (2007). Effects of postoperative epidural analgesia on immune response to surgery. Acta Med. Lith., 10, 14-16.

  • Golubovska, I., Studers, P., Vanags I. (2007). Pain relief after joint replacement surgery. RSU zinātnisko rakstu krājums. 2006. gada medicīnas nozares pētnieciskā darba publikācijas, pp. 129.-33.

  • Hafezi-Moghadam, A., Simoncin, I. T., Yang, Z. (2002). Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat. Med., 8, 473-479.

  • Hall, G. M., Peerbhoy, D., Shenkin, A., Parker, C. J., Salmon, P. (2000). Hip and knee arthroplasty: A comparison and the endocrine, metabolic and inflammatory responses. Clin. Sc., 98(1), 71-79.

  • Himmelseher, S., Ziegler-Pithamitsis, D., Argiriadou, H., Martin, J., Jelen-Esselborn, S., Kochs, E. (2001). Small-dose S(+)-ketamine reduces postoperative pain when applied with ropivacaine in epidural anesthesia for total knee arthroplasty. Anesth. Analg., 92, 1290.

  • Holte, K., Kehlet, H. (2002). Perioperative single-dose glucocorticoid administration: Pathophysiologic effects and clinical implications. J. Am. Coll. Surg., 195, 694-712.

  • Johansson, A., Dahlin, L., Kerns, J. M. (1995). Long-term local corticosteroid application does not influence nerve transmission or structure. Acta. Anaesth. Scand., 39, 364-369.

  • Joos, S. (1993). The use of glucocorticoids and non-steroidal anti-inflammatory drugs for preventive postsurgical pain relief. Bailliere's Clinical Anaesthesiology, 7(3), 318-356.

  • Kehlet, H. (2007). Glucocorticoids for peri-operative analgesia: How far are we from general recommendations? Acta. Anaesth. Scand., 51(9), 1133-1135. [Crossref] [Web of Science]

  • Langmayr, J. J., Obwegeser, A. A., Schwarz, A. B., Laimer, I., Ulmer, H., Ortler, M. (1995). Intrathecal steroids reduce pain after lumbar disc surgery: A double-blind, placebo-controlled prospective study. Pain, 62, 357-361.

  • Lavyne, M. H., Bilsky, M. H. (1992). Epidural steroids, postoperative morbidity, and recovery in patients undergoing microsurgical lumbar discectomy. J. Neurosurg., 77, 90-95.

  • Manchikanti, L. (2002). Role of neuraxial steroids in interventional pain management. Pain Phys., 5, 182-199.

  • Maillefert, J. F., Aho, S., Huguenin, M. C. (1995). Systemic effects of epidural dexamethasone injections. Rev. Rhum. Eng. Ed., 62, 429-432.

  • Marinanageli, F., Ciccoli, A., Donatelli, F., Paladini, A., Varassi, H. (2002). Uso degli steroidi per via spinale ed epidurale. Minerva Anestez., 68, 613-620.

  • McNeill, T. W., Andersson, G. B., Schell, B., Sinkora, B., Nelson, J., Lavender, S. A. (1995). Epidural administration of methylprednisolone and morphine for pain after a spinal operation. A randomized, prospective, comparative study. J. Bone. Joint. Surg., 77, 1814-1818.

  • Menger, M. D., Vollmar, B. (2004). Surgical trauma: Hyperinflammation versus immunosuppression? Langenbecks Arch. Surg., 389, 475-484.

  • Muldoon, T., Milligan, K., Quinn, P. (1998). Comparison between extradural infusion of ropivacaine or bupivacaine for the prevention of postoperative pain after total knee arthroplasty. BJA, 80, 680-681.

  • Nagelschmidt, M., Fu, Z. X., Saag, S., Dimmeler, S., Neugebauer, E. (1999). Preoperative high dose methprednisolone improves patients outcome after abdominal surgery. Eur. J. Surg., 165(10), 971-978.

  • Ontjes, D. A. (1995). Adrenal corticosteroids, corticotropin releasing hormone, adrenoconticotropin and antiadrenal drugs. In Munson, P. L. (ed.). Principles of Pharmacology, Basic Concepts and Clinical Applications. New York, NY: Chapman & Hall, pp. 749-787.

  • Reikerås, O., Helle, A., Krohn, C. D., Brox, J. I. (2008). Cytokine responses to glucocorticoids and surgery. Eur. J. Trauma. Emerg. Surg., 2, 141-148.

  • Rhen. T., Cidlowski, J. A. (2005). Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N. Engl. J. Med., 353, 1711-1723.

  • Romundstad, L., Breivik, H., Niemi, G., Stubhaug, A. (2004). Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid-sparing effects. Acta Anaesth. Scand., 48, 1223-1231.

  • Romundstad, L., Breivik, H., Roald, H., Skollberg, K., Haugen, T., Narum, J., Stubhaug, A. (2006). Methylprednisolone reduces pain, emesis and fatigue after breast augmentation surgery: A single-dose, randomized, parallel-group study with methylprednisolone 125 mg, Parecoxib 40 mg, and placebo. Anest. Analg., 102, 418-425.

  • Sauerland, S., Nagelschmidt, M., Mallmann, P., Neugebauer, E. A. (2000). Risks and benefits of preoperative high dose methylprednisolone in surgical patients: A systematic review. Drug Saf., 23(5), 449-461. [PubMed] [Crossref]

  • Schimmer, B. P., Parker, K. L. (1996). Adrenocorticotropic hormone: Adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, Hardman J. G., Limbird, L. E., Molinoff, P. B., Ruddon, R. W., Goodman Gilman A. (eds). McGraw-Hill, New York, pp. 1459-1485.

  • Schulze, S., Andersen, J., Overgaard, H. (1998). Effect of prednisolone on the systemic response and wound healing after colonic surgery. Arch. Surg., 132, 129-135.

  • Schulze, S., Sommer, P., Bigler, D. (1992). Effect of combined prednisolone, epidural analgesia, and indomethacin on the systemic response after colonic surgery. Arch. Surg., 127, 325-331.

  • Skjelbred, P., Løkken, P. (1982). Reduction of pain and swelling by a corticosteroid injected 3 hours after surgery. Eur. J. Clin. Pharm., 23(2), 141-146. [Crossref]

  • Stubhaug, A., Romunstad, L., Kaasa, T., Breivik, H. (2007). Methylprednisolone and ketorolac rapidly reduce hyperalgesia around a skin burn injury and increase pressure pain thresholds Acta Anaesth. Scand., 51, 1138-1146. [Web of Science]

  • Thomas, S., Beevi, S. (2006). Epidural dexamethasone reduces postoperative pain and analgesic requirements. Can. J. Anesth., 59(9), 899-905. [Crossref]

  • Wang, Y. L., Tan, P. P., Yang, C. H., Tsai, S. C., Chung, H. S. (1997). Epidural dexamethasone reduces the incidence of backache after lumbar epidural anesthesia. Anesth. Analg., 84, 376-378.

  • Watanabe, S., Bruera, E. (1994). Corticosteroids as adjuvant analgesics. J. Pain. Symptom. Managem., 9, 442-445.

  • Yeager, M. P., Guyre, P. M., Munck, A. U. (2004). Glucocorticoid regulation of the inflammatory response to injury. Acta. Anaesth. Scand., 48(7), 799-813. [Crossref]

About the article


Published Online: 2008-11-29

Published in Print: 2008-01-01


Citation Information: Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences., ISSN (Print) 1407-009X, DOI: https://doi.org/10.2478/v10046-008-0020-3. Export Citation

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