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