Open Access Open Access  Restricted Access Subscription or Fee Access

A review of epidural and intrathecal opioids used in the management of postoperative pain

Borja Mugabure Bujedo, MD, Silvia González Santos, MD, Amaia Uría Azpiazu, MD

Abstract


Opioids are the most potent centrally acting analgesic drugs for the treatment of pain. For the past years, since the discovery of spinal opioid receptors, the use of spinal opioids has been adopted in clinical practice in the hope of producing intense segmental analgesia that was devoid of the dose-limiting side effects associated with systemic opioid administration. Experimental studies have demonstrated that after their perispinal administration, liposolubility is inversely proportional to their spinal selectivity, which is higher for the most water-soluble drug, morphine, than for other more lipophilic drugs, such as fentanyl and sufentanil. Clinical trials have shown that epidural morphine in the form of extended-release liposome injections gives good analgesia for a period of 48 hours, with no need for epidural catheterization. Conversely, fentanyl is the most appropriate opioid in ambulatory surgery and seems to have the strongest effect at the spinal cord administered epidurally as a bolus and supraspinally using continuous epidural infusion. Epidural methadone and hydromorphone are suitable alternatives for analgesia in the postoperative period, given that they have intermediate pharmacokinetic characteristics with respect to the two aforementioned groups of opioids. All opioids administered intrathecally will produce some degree of spinally mediated analgesia. The main differences are related to their duration of action, rate of clearance, and the pathways by which the drugs reach their receptors in the brain. In general, lipophilic opioids produce short-term analgesia (1-4 hours), which is very useful for immediate postoperative pain. However, morphine produces intense analgesia for up to 24 hours with doses as low as 100 µg.


Keywords


spinal analgesia, epidural opioids, intrathecal opioids, postoperative pain

Full Text:

PDF

References


Brill S, Gurman GM, Fisher A: A history of neuroaxial administration of local analgesics and opioids. Eur J Anesthesiol. 2003; 20(9): 682-689.

Yaksh TL, Rudy TA: Analgesia mediated by a direct spinal action of narcotics. Science. 1976; 192(4246): 1357-1358.

Wang JK, Nauss LA, Thomas JE: Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979; 50(2): 149-151.

Behar M, Magora F, Olshwang D, et al.: Epidural morphine in treatment of pain. Lancet. 1979; 1(8115): 527-529.

Bernards CM: Understanding the physiology and pharmacology of epidural and intrathecal opioids. Best Pract Res Clin Anaesthesiol. 2002; 16(4): 489-505.

Bernards CM: Recent insights into the pharmacokinetics of spinal opioids and the relevance to opioid selection. Curr Opin Anaesthesiol. 2004; 17(5): 441-447.

de Leon-Casasola OA, Lema MJ: Postoperative epidural opioid analgesia: What are the choices? Anesth Analg. 1996; 83(4): 867-875.

Bernards CM, Shen DD, Sterling ES, et al.: Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): Differences among opioids. Anesthesiology. 2003; 99(2): 455-465.

Ummerhofer WC, Arends RH, Shen DD, et al.: Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanyl. Anesthesiology. 2000; 92(3): 739-753.

Rathmell JP, Lair TR, Nauman B: The role of intrathecal drugs in the treatment of acute pain. Anesth Analg. 2005; 101(5 Suppl): S30-S43.

Meylan N, Elia N, Lysakowski C, et al.: Benefit and risk of intrathecal morphine without local anaesthesic in patients undergoing major surgery: Meta-analysis of randomized trials. Br J Anaesth. 2009; 102102(2): 156-167.

Hamber EA, Viscomi CM: Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med. 1999; 24(3): 255-263.

Ginosar Y, Riley ET, Angst MS: The site of action of epidural fentanyl in humans: The difference between infusion and bolus administration. Anesth Analg. 2003; 97(5): 1428-1438.

Lilker S, Rofaeel A, Balki M, et al.: Comparison of fentanyl and sufentanil as adjuncts to bupivacaine for labor epidural analgesia. J Clin Anesth. 2009; 21(2): 108-112.

Ngan Kee WD: Epidural pethidine: Pharmacology and clinical experience. Anaesth Intensive Care. 1998; 26(3): 247-255.

Boas RA, Villiger JW: Clinical actions of fentanyl and buprenorphine. The significance of receptor binding. Br J Anaesth. 1985; 57(2): 192-196.

Bullingham RE, McQuay HJ, Moore A, et al.: Buprenorphine kinetics. Clin Pharmacol Ther. 1980; 28(5): 667-672.

Naito H: Pharmacokinetics of intravenous and epidural buprenorphine analgesia. Masui. 1988; 37(10): 1180-1190.

Coda BA, Brown MC, Risler L, et al.: Equivalent analgesia and side effects during epidural and pharmacokinetically tailored intravenous infusion with matching plasma alfentanil concentration. Anesthesiology. 1999; 90(1): 98-108.

van der Nieuwenhuyzen MC, Stienstra R, Burm AG, et al.: Alfentanil as an adjuvant to epidural bupivacaine in the management of postoperative pain after laparotomies: Lack of evidence of spinal action. Anesth Analg. 1998; 86(3): 574-578.

Chauvin M, Hongnat JM, Mourgeon E, et al.: Equivalence of postoperative analgesia with patient-controlled intravenous and epidural alfentanil. Anesth Analg. 1993; 76(6): 1251-1258.

Turker G, Goren S, Bayram S, et al.: Comparison of lumbar epidural tramadol and lumbar epidural morphine for pain relief after thoracotomy: A repeated-dose study. J Cardiothorac Vasc Anesth. 2005; 19(4): 468-474.

Kim T, Murdande S, Gruber A, et al.: Sustained-release morphine for epidural analgesia in rats. Anesthesiology. 1996; 85(2): 331-338.

Ready LB: Acute pain: Lessons learned from 25,000 patients. Reg Anesth Pain Med. 1999; 24(6): 499-505.

Heitz JW, Witkowski TA, Viscusi ER: New and emerging analgesics and analgesic technologies for acute pain management. Curr Opin Anaesthesiol. 2009; 22(5): 608-617.

Gambling D, Hughes T, Martin G, et al.: A comparison of Depodur™, a novel, single dose extended epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery. Anesth Analg. 2005; 100(4): 1065-1074.

Viscusi ER: Emerging techniques in the management of acute pain: Epidural analgesia. Anesth Analg. 2005; 101(5 suppl): S23-S29.

Sumida S, Lesley MR, Hanna MN, et al.: Meta-analysis of the effect of extended-release epidural morphine versus intravenous patient-controlled analgesia on respiratory depression. J Opioid Manag. 2009; 5(5): 301-305.

Mhuircheartaigh RJ, Moore RA, McQuay HJ: Analysis of individual patient data from clinical trials: Epidural morphine for postoperative pain. Br J Anaesth. 2009; 103(6): 874-881.

Halpern SH, Arellano R, Preston R, et al.: Epidural morphine vs hydromorphone in post-caesarean sections patients. Can J Anaesth. 1996; 43(6): 595-598.

Chestnut DH, Choi WW, Isbell TJ: Epidural hydromorphone for postcesarean analgesia. Obstet Gynecol. 1986; 68(1): 65-69.

Henderson SK, Mattew E, Cohen H, et al.: Epidural hydromorphone: A double-blind comparison with intramuscular hydromorphone for postcesarean section analgesia. Anesthesiology. 1987; 66(6): 825-830.

Cousins MJ, Mather LE: Intrathecal and epidural administration of opioids. Anesthesiology. 1984; 61(3): 276-310.

Liu S, Carpenter RL, Mulroy MF, et al.: Intravenous versus epidural administration of hydromorphone. Effects on analgesia and recovery after radical retropubic prostatectomy. Anesthesiology. 1995; 82(3): 682-688.

Liu SS, Bieltz M, Wukovits B, et al.: Prospective survey of patient-controlled epidural analgesia with bupivacaine and hydromorphone in 3736 postoperative orthopedic patients. Reg Anesth Pain Med. 2010; 35: 351-354.

Chaplan SR, Duncan SR, Brodsky JB, et al.: Morphine and hydromorphone epidural analgesia. A prospective, randomized comparison. Anesthesiology. 1992; 77(6): 1090-1994.

Mulroy MF: Epidural hydromorphone: A step closer to the view from the top. Reg Anesth Pain Med. 2010; 35(4): 333-334.

Peng PWH, Tumber PS, Gourlay D: Perioperative pain management for patients on methadone therapy. Can J Anesth. 2005; 52(5): 513-523.

Garrido MJ, Troconiz IF: Methadone: A review of its pharmacokinetic/pharmacodynamics properties. J Pharmacol Toxicol. 1999; 42(2): 61-66.

Prieto-Alvarez P, Tello-Galindo I, Cuenca-Peña J, et al.: Continuous epidural infusion of racemic methadone results in effective postoperative analgesia and low plasma concentrations. Can J Anaesth. 2002; 49(1): 25-31.

Parramon F, Garcia CH, Gamboes P, et al.: Postoperative patient-controlled analgesia is more effective with epidural methadone than with intravenous methadone in thoracic surgery. Rev Esp Anestesiol Reanim. 2003; 50(7): 326-331.

Lugo RA, Kern SE: The pharmacokinetics of oxycodone. J Pain Palliat Care Pharmacother. 2004; 18(4): 17-30.

Pöyhiä R, Kalso EA: Antinociceptive effects and central nervous system depression caused by oxycodone and morphine in rats. Pharmacol Toxicol. 1992; 70(2): 125-130.

Backlund M, Lindgren L, Kajimoto Y, et al.: Comparison of epidural morphine and oxycodone for pain after abdominal surgery. J Clin Anesth. 1997; 9(1): 30-35.

Yanagidate F, Dohi S: Epidural oxycodone or morphine following gynaecological surgery. Br J Anaesth. 2004; 93(3): 362-367.

Glass PS, Estok P, Ginsberg B, et al.: Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration. Anesth Analg. 1992; 74(3): 345-351.

Sandler AN, Stringer D, Panos L, et al.: A randomized, double blind comparison of lumbar epidural and intravenous fentanyl infusions for postthoracotomy pain relief. Anesthesiology. 1992; 77(4): 626-634.

Loper LA, Ready LB, Downey M, et al.: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg. 1990; 70(1): 72-75.

Ellis DJ, Millar WL, Reisner LS, et al.: A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after caesarean section. Anesthesiology. 1990; 72(6): 981-986.

Guinard JP, Mavrocordatos P, Chiolero R, et al.: A randomized comparison of intravenous versus lumbar and thoracic epidural fentanyl for analgesia after thoracotomy. Anesthesiology. 1992; 77(6): 1108-1115.

Coda B, Brown MC, Schaffer R, et al.: Pharmacology of epidural fentanyl, alfentanyl and sufentanil in volunteers. Anesthesiology. 1994; 81(5): 1149-1161.

Salomaki TE, Laitinen JO, Nuutinen LS: A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy. Anesthesiology. 1991; 75(5): 790-795.

Welchew EA, Breem DP: Patient-controlled on-demand epidural fentanyl: A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. Anaesthesia. 1991; 46(6): 438-441.

Grant RP, Dolman JF, Harper JA, et al.: Patient-controlled lumbar epidural fentanyl compared with patient-controlled intravenous fentanyl for postthoracotomy pain. Can J Anaesth. 1992; 39(3): 214-219.

George MJ: The site of action of epidurally administered opioids and its relevance to postoperative pain management. Anaesthesia. 2006; 61(7): 659-664.

Miguel R, Barlow I, Morrell M, et al.: A prospective, randomized, double-blind comparison of epidural and intravenous sufentanil infusions. Anesthesiology. 1994; 81(2): 346-352.

Geller E, Chrubasik J, Graf R, et al.: A randomized double-blind comparison of epidural sufentanil versus intravenous sufentanil or epidural fentanyl analgesia after major abdominal surgery. Anesth Analg. 1993; 76(6): 1243-1250.

Swenson JD, Hullander RM, Bready RJ, et al.: A comparison of patient controlled epidural analgesia with sufentanil by the lumbar versus thoracic route after thoracotomy. Anesth Analg. 1994; 78(2): 215-218.

Knape JT: Early respiratory depression resistant to naloxone following epidural buprenorphine. Anesthesiology. 1986; 64(3): 382-384.

van Dorp E, Yassen A, Sarton E, et al.: Naloxone reversal of buprenorphine-induced respiratory depression. Anesthesiology. 2006; 105(1): 51-57.

Inagaki Y, Mashimo T, Yoshiya I: Mode and site of analgesic action of epidural buprenorphine in humans. Anesth Analg. 1996; 83(3): 530-536.

Hashimoto K, Monma F, Amagasa M, et al.: Prospective study on anesthesia for lumbar spine surgery: The effectiveness of the perioperative epidural anesthesia with buprenorphine. Masui. 2009; 58(6): 708-712.

Ipe S, Korula S, Varma S, et al.: A comparative study of intrathecal and epidural buprenorphine using combined spinalepidural technique for caesarean section. Indian J Anaesth. 2010; 54(3): 205-209.

Husemeyer RP, Cummings AJ, Rosankiewicz JR, et al.: A study of pethidine and analgesia in women in labour following intravenous, intramuscular and epidural administration. Br J Clin Pharmacol. 1982; 13(2): 171-176.

Paech MJ, Moore JS, Evans SF: Meperidine for patient-controlled analgesia after caesarean section. Intravenous versus epidural administration. Anesthesiology. 1994; 80(6): 1268-1276.

Al-Tamimi Y, IIet KF, Paech MJ, et al.: Estimation of infant dose and exposure to pethidine and norpethidine via breast milk following patient-controlled epidural pethidine for analgesia post caesarean delivery. Int J Obstet Anesth. 2011; 20(2): 128-134.

Chen PP, Cheam EW, Ma M, et al.: Patient-controlled pethidine after major upper abdominal surgery: Comparison of the epidural and intravenous routes. Anaesthesia. 2001; 56(11): 1106-1112.

Kehlet H, Wilkinson RC, Fisher HB, et al.: PROSPECT: Evidence-based, procedure-specific postoperative pain management. Best Pract Res Clin Anaesthesiol. 2007; 21(1): 149-159.

Elia N, Lysakowski C, Tramèr MR: Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs or selective ciclooxygenase-2 inhibitors and patient controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology. 2005; 103(6): 1296-1304.

Remy C, Marret E, Bonnet F: Effects of acetaminophen on morphine side effects and consumption after major surgery: Meta-analysis of randomized controlled trials. Br J Anaesth. 2005; 94(4): 505-513.

Gehling M, Tryba M: Risks and side-effects of intrathecal morphine combined with spinal anaesthesia: A meta-analysis. Anaesthesia. 2009; 64(6): 643-651.

Gehling MH, Luesebrink T, Kulka PJ, et al.: The effective duration of analgesia after intrathecal morphine in patients without additional opioid analgesia: A randomized doubleblind multicentre study on orthopaedic patients. Eur J Anaesthesiol. 2009; 26(6): 683-688.

Bailey PL, Rhondeau S, Schafer PG, et al.: Dose-response pharmacology of intrathecal morphine in human volunteers. Anesthesiology. 1993; 79(1): 49-59.

Herman NL, Calicott R, Van Decar TK, et al.: Determination of the dose-response relationship for intrathecal sufentanil in laboring patients. Anesth Analg. 1997; 84(6): 1256-1261.

Nelson KE, Rauch T, Terebuh V, et al.: A comparison of intrathecal fentanyl and sufentanil for labor analgesia. Anesthesiology. 2002; 96(5): 1070-1073.

Palmer CM, Cork RC, Hays R, et al.: The dose-response relation of intrathecal fentanyl for labor analgesia. Anesthesiology. 1998; 88(2): 355-361.

Dahl JB, Jeppensen IS, Jorgensen H, et al.: Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing caesarean section with spinal anesthesia: A qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology. 1999; 91(6): 1919-1927.

Giovannelli M, Bedforth N, Aitkenhead A: Survey of intrathecal opioid usage in the UK. Eur J Anaesthesiol. 2008; 25(2): 118-122.

Husaini SW, Russell IF: Intrathecal diamorphine compared with morphine for postoperative analgesia after caesarean section under spinal anaesthesia. Br J Anaesth. 1998; 81(2): 135-139.

Saravanan S, Robinson AP, Qayoum Dar A, et al.: Minimum dose of intrathecal diamorphine required to prevent intraoperative supplementation of spinal anaesthesia for caesarean section. Br J Anaesth. 2003; 91(3): 368-372.

Sakai T, Use T, Shimamoto H, et al.: Mini-dose (0.05 mg) intrathecal morphine provides effective analgesia after transurethral resection of the prostate. Can J Anaesth. 2003; 50(10): 1027-1030.

Murphy PM, Stack D, Kinirons B, et al.: Optimizing the dose of intrathecal morphine in older patients undergoing hip arthrosplasty. Anesth Analg. 2003; 97(6): 1709-1715.

Rathmell JP, Pino CA, Taylor R, et al.: Intrathecal morphine for postoperative analgesia: A randomized, controlled, doseranging after hip and knee arthrosplasty. Anesth Analg. 2003; 97(5): 1452-1457.

Ziegeler S, Fritsch E, Bauer C, et al.: Therapeutic effect of intrathecal morphine after posterior lumbar interbody fusion surgery: A prospective, double-blind, randomized study. Spine. 2008; 33(22): 2379-2386.

Liu N, Kuhlman G, Dalibon N, et al.: A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain. Anesth Analg. 2001; 92(1): 31-36.

Zisman E, Shenderey A, Ammar R, et al.: The effects of intrathecal morphine on patients undergoing minimally invasive direct coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2005; 19(1): 40-43.

Turker G, Goren S, Sahin S, et al.: Combination of intrathecal morphine and remifentanil infusion for fast-track anesthesia in off-pump coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2005; 19(6): 708-713.

Fléron MH, Weiskopf RB, Bertrand M, et al.: A comparison of intrathecal opioid and intravenous analgesia for the incidence of cardiovascular, respiratory, and renal complications after abdominal aortic surgery. Anesth Analg. 2003; 97(1): 2-12.

Rebel A, Sloan P, Andrykowsky M: Retrospective analysis of high-dose intrathecal morphine for analgesia after pelvic surgery. Pain Res Manag. 2011; 16(1): 19-26.

Quigley C: Hydromorphone for acute and chronic pain. Cochrane Database Syst Rev. 2002; (1): CD003447.

Drakeford MK, Pettine KA, Brookshire L, et al.: Spinal narcotics for postoperative analgesia in total joint arthroplasty. A prospective study. J Bone Joint Surg Am. 1991; 73(3): 424-428.

Jacobson L, Chabal C, Brody MC, et al.: Intrathecal methadone and morphine for postoperative analgesia: A comparison of the efficacy, duration and side effects. Anesthesiology. 1989; 70(5): 742-746.

Jacobson L, Chabal C, Brody MC, et al.: Intrathecal methadone: A dose-response study and comparison with intrathecal morphine 0.5 mg. Pain. 1990; 43(2): 141-148.

Moore A, Bullingham R, McQuay H, et al.: Spinal fluid kinetics of morphine and heroin. Clin Pharmacol Ther. 1984; 35(1): 40-55.

Kotob HI, Hand CW, Moore RA, et al.: Intrathecal morphine and heroin in humans: Six hours drug levels in spinal fluid and plasma. Anesth Analg. 1896; 65(7): 718-722.

Ehikhametalor KO, Nelson M: Intrathecal pethidine as sole anaesthetic agent for operative procedures of the lower limb, inguinal area and perineum. West Indian Med J. 2001; 50(4): 313-316.

Hansen D, Hansen S: The effects of three graded doses of meperidine for spinal anesthesia in African men. Anesth Analg. 1999; 88(4): 827-830.

Yu SC, Ngan Kee WD, Kwan AS: Intrathecal meperidine and shivering in obstetric anesthesia. Anesth Analg. 2004; 99(4): 1272-1273.

Olofsson C, Nygards EB, Bjersten AB, et al.: Low-dose bupivacaine with sufentanil prevents hypotension after spinal anesthesia for hip repair in elderly patients. Acta Anaesthesiol Scand. 2004; 48(10): 1240-1244.

Ben-David B, Frankel R, Arzumonov T, et al.: Minidose bupivacaine-fentanyl spinal anesthesia for surgical repair of hip fracture in the aged. Anesthesiology. 2000; 92(1): 6-10.

Kim SY, Cho JE, Hong JY, et al.: Comparison of intrathecal fentanyl and sufentanil in low-dose dilute bupivacaine spinal anaesthesia for transurethral prostatectomy. Br J Anaesth. 2009; 103(5): 750-754.

Richardson MG, Wissler RN: Densities of dextrose-free intrathecal local anesthetics, opioids, and combinations measured at 37 degrees C. Anesth Analg. 1997; 84(1): 95-99.

Imbelloni LE, Moreira AD, Gaspar FC, et al.: Assessment of the densities of local anesthetics and their combination with adjuvants: An experimental study. Rev Bras Anestesiol. 2009; 59(2): 154-165.

Mugabure Bujedo B, Tranque Bizueta I, González Santos S, et al.: Multimodal approaches to postoperative pain management and convalescence. Rev Esp Anestesiol Reanim. 2007; 54(1): 29-40.




DOI: https://doi.org/10.5055/jom.2012.0114

Refbacks

  • There are currently no refbacks.